EUT Congress News - Saturday 17 March

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33rd 32nd Annual Annual Congress Congress of of the the European European Association Association of of Urology Urology

Saturday, 17 25March March2018 2017

Copenhagen, 16-20 March 2018 London, 24-28 2017

Meeting the challenges in urogenital diseases EU Health Commissioner Andriukaitis urges stronger collaboration

By Joel Vega and Erika de Groot

currently numbers 29 active units in 11 EU member states.

To the rhythmic, high energy beat of the synchronized, four-man Copenhagen Drummers band, the 33rd Annual EAU Congress opened yesterday with European Commissioner for Health and Food Safety, Prof. Vytenis Andriukaitis (LT) urging the audience to collaborate in the European Reference Networks (ERNs).

Chapple also highlighted the crucial role of the EU in creating the ERNs which he said will lead to better data collection and mutual collaboration among European scientists and clinical professionals. “To ensure the sustainability of this project we need to form partnerships and work on common goals,” he said.

“This flagship project reflects not only the need to further strengthen our collaboration, but also the fact that we can and have achieved a lot if we put together our resources, knowledge and commitment,” said Andriukaitis. He emphasized that the synergies of expert centres are invaluable and will come a long way in providing better healthcare, particularly to those with rare diseases.

The Opening Ceremony traditionally highlights the EAU’s honorary members and awardees. Chapple conferred the title of Honorary Members to Gunnar Aus (SE), Patrick Coloby (FR), Mani Menon (US) and Ajit Vaze (IN). Prof. Vicenzo Mirone (IT) received the EAU Willy Gregoir Medal 2018. Prof. Didier Jacqmin (FR) was awarded the EAU Frans Debruyne Lifetime Achievement Award, while Prof. Selcuk Silay (TR) won the EAU Crystal Matula Award.

Andriukaitis thanked EAU Secretary General Prof.

Chris Chapple for his personal efforts and commitment to ERNs with the involvement of urological expertise in the eUROGEN network which

“For urologists our biggest concern is how to boost our medical and surgical strategies, and balance these without neglecting our core competencies,” said Mirone.

New agents and imaging to improve PCa therapies Experts’ forecasts at ESO Prostate Cancer Observatory There is a range of new agents, molecular markers and improved imaging techniques that over the coming years will help doctors to further optimise their management of prostate cancer patients, particularly those with advanced or high-risk disease.

During the 5th European School of Oncology (ESO) Prostate Cancer Observatory held yesterday, a panel of prostate cancer (PCa) specialists presented their expectations for promising medical approaches that aim to boost the current management of PCa. The multidisciplinary presentations covered new developments and forecasts for research, surgery, active surveillance, imaging, pathology, and medical oncology. The perspective and concerns of patient groups were also discussed by Prof. Louis Denis (BE) as a representive for these groups.

“My expectations for 2018 and next year are further results from STAMPEDE and the potential changes in the standard of care for metastatic hormone-naïve prostate cancer (mHNPC) patients,” said medical oncologist Dr. Ananya Choudhury (GB) who gave the view from her discipline.

Choudhury added that results are awaited from sequencing and combination studies. She mentioned hormonal agents being tested in trials such as SPARTAN (Apalutamide), PROSPER (Enzalutamide), STAMPEDE/LATITUDE (abiraterone) as well as STAMPEDE, which is testing the combination of abiraterone and enzalutamide.

Giving the urological perspective on active surveillance (AS), Prof. Karim Touijer (US) stressed its importance and noted that its increasing use necessitates educating the physician in order to provide better counselling to patients. Touijer stated that it is important is to collect more information on AS and to reassure the patient about future treatment options.

Saturday, 17 March 2018

Dr. Deepansh Dalela (US) received the Hans Marberger Award for the best European paper published on minimally invasive surgery in urology. Prof. Sergio Musitelli (IT) received the first

Commissioner V. Andriukaitis: “Synergies across Europe are invaluable.”

African and European views on HIV and circumcision

By Erika de Groot Ethics and human rights. Medical safety concerns.

These are factors that differentiate African and European views on the role of circumcision in HIV prevention as discussed today in the Joint Session of the European Association of Urology (EAU) and the Pan-African Urological Surgeons Association (PAUSA) chaired by Dr. Allen Chiura (ZW) and Prof. Dr. Rien Nijman (NL).

Full audience at the 5th ESO Prostate Cancer Observatory

Prof. Steven Joniau (BE), who co-chaired the session with Prof. Riccardo Valdagni (IT), said: “For me, the session showed that we need to better understand the disease with the aid of the many tools we have now such as PSMA, MRI and others, in combination with the standard tests such as PSA. Tools such as PSA still have their use despite the entrance of new methods. It is important to avoid over-treatment and instead focus on the detection and treatment of high-risk cancers.”

EAU Ernest Desnos Prize for his contributions to urological history, while Hashim Ahmed (GB) was awarded the EAU Prostate Cancer Research Award.

In his lecture Successes and Challenges of Male Circumcision in the HIV era, Dr. Tonderayi Mangwiro (ZW) stated that male circumcision (MC) averts a greater incidence of ulcerative sexually-transmitted infections (STIs) and the susceptibility of the foreskin to abrasions during intercourse.

Additional benefits include lower incidence of urinary tract infection in infants, penile hygiene, and prevention of balanitis and posthitis. The risk of penile cancer is also lowered. Mangwiro said that MC is “not a silver bullet.” It has a 60% efficacy and should be used as part of a comprehensive HIV programme.

According to Mangwiro, the VMMC (voluntary medical male circumcision) programme has done well; it has achieved its scale up targets and is currently developing a new strategy that will introduce a sustainability component.

Dr. Nicolai Lohse (DK) listed varying recommendations for neonatal MC in Europe, Canada and the United States.

Joniau reiterated Touijer’s key message as he stressed the importance of AS to avoid over-treatment of low-risk PCa. Dr. Ivo Schoots (NL) discussed prostate MRI and its diagnostic accuracy, noting that a limitation of MRI is disagreement among radiologists. “There are now proposed adjustments to the PIRADS text,” said Schoots. “Looking back, to 2017, prostate MRI shows maturation with its strength and limitations.”

Prof. Rodolfo Montironi (IT) discussed developments in pathology such as the update of PCa grading, intraductal carcinoma of the prostate, the routine molecular markers used by pathologists with multiple clinical purposes, and the potential of liquid biopsies such as urine and blood.

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Today’s Industry Sessions & Workshop Industry sessions and workshop, all starting at 18:00 hrs

History Office Special Session Exploring history of urology in Denmark, Scandinavia and beyond

By Loek Keizer

Multi-disciplinary team (MDT) perspectives for early, optimised treatment of mCRPC ASTELLAS PHARMA EUROPE LTD. Green Area, Room 1 (Level 0) Optimising patient management in urogenital cancers IPSEN PHARMA Green Area, Room 2 (Level 0)

The interconnectedness of urology in Europe is exemplified by the collaboration evident in the Scandinavian countries and the Scandinavian Association of Urology in particular.

On the first day of EAU18, the 33rd Annual EAU Congress, held this year in Copenhagen, the EAU History Office welcomed prominent Danish and Scandinavian speakers to give the audience a flavour of the long history of regional cooperation, as well as some biographies of eminent Danish urological pioneers.

Later in the Specialty Session, EAU History Office Chairman Prof. Philip Van Kerrebroeck (NL) gave some background information on the new EAU Ernest Desnos Prize, Dr. Johan Mattelaer (BE) gave a preview of his latest book, and Mr. Jonathan Goddard (GB) looked at the role of British urologists in the First World War, with 2018 marking the centenary of the end of the war.

Looking beyond mLUTS to BPE and BOO: Does it really matter?

RECORDATI SPA Red Area, Room 1 (Level 0) Combating UTI – Shifts of paradigm BIONORICA Blue Area, Room 5 (Level 0)

Establishing a Nordic Society Prof. Christian Beisland (NO) spoke about the extensive history of urology in the Scandinavian countries as well as the establishment of an international urological association for the region.

Workshop Bladder EpiCheck – Breaking the glass ceiling of urine markers in NMIBC monitoring NUCLEIX Green Area, Room 10 (Level 1)

Initially, the Association had a fixed quota of members from each country, although over time this arrangement was replaced by automatic membership when a urologist joined their respective national society. Iceland joined the Association in 1976.

Beisland said: “The Nordic Surgical Society (NKF) was first founded in 1893, making it one of the oldest

Prof. Beisland, speaking about the history of the Scandinavian Association of Urology.

surgical societies in the world. It was a relatively slow process of separating urology from general surgery, with the first national societies being established in the 1950s and 1960s.”

In 1950, the Scandinavian Association of Urology laid its foundations as an informal group, a ‘travelling club’ for urologists in Denmark, joined later by urologists from Norway, Sweden and Finland. In 1956, a proposal was made to formalise this arrangement in a proper Association, albeit with some initial scepticism by representatives from Norway and Sweden. Beisland: “In the end, the Association was famously founded in the sauna of Professor Tuovinen’s summer house in Ojakkala, Finland.”

Since 1995, the official language of the Association has been “bad English” (as opposed to “bad Swedish” – the words of Prof. Jens Andersen (DK)).

The decision to switch to English was made in order to be more inclusive to the Finnish delegates and also to attract greater international interest. Prof.

Andersen recollected that board of the Scandinavian Association had a lot of discussion at the time, amid fears of a loss of national identity.

Holm and Hald Drs. Jorgen Kvist Kristensen (DK) and Jørgen Nordling (DK) presented biographies of Profs. Hans Henrik Holm and Tage Hald (DK) respectively, two incredibly influential and respected urologists. Holm was a pioneer in interventional ultrasound, combining ultrasound with biopsies, treatment of cysts and percutaneous nephrostomy in the 1960s.

Tage Hald, the 1999 Willy Gregoir Award Winner, was a founding member of the International Continence Society, and was tasked with establishing uniform terminology in that field. “He was a much-admired tutor and he supervised a huge range of topics as Professor at Herlev Hospital,” Nordling concluded.

Robotics not a priority in developing world European Urology Today

Joint EAU-SIU session tackles controversial issues in urology

By Joel Vega

Editor-in-Chief Prof. M. Wirth, Dresden (DE)

Costly robot-assisted surgery is not viable in the developing world considering that there is no convincing data on the superiority of these expensive robot technologies, says a UK-based expert.

Section Editors Prof. T. E. Bjerklund Johansen, Oslo (NO) Mr. Ph. Cornford, Liverpool (GB) Prof. O. Hakenberg, Rostock (DE) Prof. P. Meria, Paris (FR) Dr. G. Ploussard, Paris (FR) Prof. J. Rassweiler, Heilbronn (DE) Prof. O. Reich, Munich (DE) Dr. F. Sanguedolce, London (GB) Dr. Z. Zotter, Budapest (HU)

During the joint EAU- Société Internationale d’Urologie (SIU) session, part of the Urology Beyond Europe programme, experts clashed on the perceived importance of robot-assisted surgeries particularly in prostate disease.

Founding Editor Prof. F. Debruyne, Nijmegen (NL)

“Strive to become a better surgeon, particularly if you are in the developing world. Stop obsessing about technology… There are no differences in outcomes,” said Prof. Prokar Dasgupta (GB). “Only 5% of operations are robotic. The cost of robot-assisted procedures rose by 13% in three years, resulting in around $2.5 billion in additional healthcare costs. The robot is an unnecessary luxury in the developing world.”

Editing and Coordination J. Vega Onsite Reporting and Editing E. de Groot L. Keizer J. Tidman J. Vega X. Zheng

Dasgupta rebutted the arguments of Dr. Sudhir Rawal (IN) noting that a centre needs to perform over 100 cases of robot-assisted surgery in order for it to be cost-effective. He also examined the issue of a shorter hospital stay, stating that hospital stay depends on the country where the patient lives.

Communications and Promotion J. Bloemberg M. van Gurp I. Moerkerken Advertising R. A. Matser L. Schreuder

Conversely, Rawal anchored his arguments within the context of the Indian experience where he said there is a clear need for a more efficient alternative to open and laparoscopic approaches. He noted that there are opportunities to save money with robotic surgeries, and mentioned that robotic procedures in India are much less expensive when compared, for instance, with the United States. He also insisted that there are clear benefits in terms of blood loss, warm ischemia time, and a shorter learning curve for surgeons compared to laparoscopy.

The session also covered some other key controversies in uro-oncology. Prof. Axel Bex (NL) argued that lymphadenectomy in renal cancer is unnecessary, against the pro-statements of Dr. Frederic Pouliot (CA), whilst Profs. Shin Egawa (JP) and Fred Witjes (NL) debated the merits of metastasectomy in urothelial cancer and Profs. Peter Wiklund ( SE) and Paolo Gontero (IT) discussed the necessity of intracorporeal diversion.

Bex said the likelihood of lymph node involvement is small and the low overall rate of local recurrence does not seem to be altered by lymphadenectomy.

“Between 58 to 95% of patients with lymph node

P. Dasgupta stresses a point during his lecture on the role of robotic surgery in developing countries.

involvement have distant metastases anyway,” he said.

Witjes opposed Egawa on urothelial cancer, arguing that metastasectomy is of limited use. “There is almost no role for surgery in metastatic UC, but in selected cases removal of initial or recurrent metastatic disease can increase cancer specific survival (CSS).”

The session also took up other issues in general urology such as social media in clinical medicine.

Prof. Declan Murphy (AU) argued against Prof. Jim Catto (GB) with the latter warning of the potential disadvantages of frequent social media use, such as loss of confidentiality, the limited understanding of complex issues that cannot be properly examined on social media platforms, and the loss of a doctor’s professional boundaries.

Biomarkers: A new pillar in diagnosis of BCa?

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Major shift in EAU Guidelines anticipated

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Prof. Arnulf Stenzl (DE), Scientific Congress Office Chairman looked back on a well-attended Specialty Session on bladder cancer on Friday, the first day of EAU18. The session consisted of a series of casebased debates between some of the biggest names in uro-oncology.

The wide variety of debates had a common theme: biomarkers are maturing as a third pillar in diagnosis.

Stenzl: “We don’t want to rely just on the pathologist, so we’ve used clinical assessment as well. And now the use of biomarkers is evolving into a feasible third pillar.”

“All these discussions took place in areas where the EAU Guidelines are not conclusive. Urologists

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“It has nothing to do with the surgery,” said Dasgupta, adding“a fool with a tool is still a fool.”

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need to find more data, and we are getting closer.

You could almost say that it’s done. Several speakers and audience members are already using molecular markers, despite not being in the guidelines.”

Despite not being part of the EAU Guidelines recommendations yet, Prof. Stenzl anticipates a “major shift” in the coming years. “This is a pressing issue, there’s a lot of uncertainty at the moment. We know that these things will be changing, there’s not been a change for decades in bladder cancer Guidelines. Studies with thousands of patients are being published. There is an unmet need, and there is good data. I expect a change to the EAU Bladder Cancer Guidelines soon.”

Debate “winners” Experts like Profs. David McConkey (USA), Joan Palou (ES), Maurizio Brausi (IT) and Jim Catto (GB) presented cases and led discussions on topics like cystoscopy, treatment options following molecular classification and what to do when BCG fails.

“It’s hard to say that there were winners in these ‘debates’,” Prof. Stenzl conceded. “This topic is much too sophisticated and grey to have clear “winners”. Nevertheless, this session was one of the most important and well-attended of the day.

These kinds of case-based debate sessions could be something we will be seeing more of at the Annual Congress.”

Saturday, 17 March 2018

Raising the next generation of key opinion leaders Young Academic Urologists report on recent achievements

By Jen Tidman The Young Academic Urologists (YAU) showcased the achievements of their talented and alreadyrenowned members at a specialty session. Dr. Michiel Sedelaar (NL) introduced Chairman Prof.

Selçuk Silay (TR) who has not only expertly guided the YAU over the past two years, but is also this year’s Crystal Matula award winner.

Silay ran through the accomplishments of the group over the six years since its inception. 84% of YAU members are presenting at EAU18, 44.1% have received a local or international scientific award, 37.7% are journal editors or associate editors, 19.4% have presentation or hands-on tutor responsibilities at ESU courses, 50.6% are involved in the EAU Sections, 11.6% are involved in Guidelines panels, four members have won Matula awards, and over 80 PubMed papers have been published (21 in 2017). The group has also contributed to EAU Section and Regional meetings, organised its own specific meetings, and at EAU18 will be running courses on presentation and leadership skills.

Through teamwork and a formula of “enthusiasm + trust + respect”, the YAU is raising the next

generation of key opinion leaders, award winners and Association of Academic European Urologists members. “The future belongs to those who believe in the beauty of their dreams,” said Silay, quoting Eleanor Roosevelt. He encouraged EAU members under 40, affiliated to an academic institution, and with at least five publications to their names, to apply to join the group.

Prof. Chris Chapple (GB), giving the Secretary General’s perspective of the role of YAU within EAU, said the Executive and Board were very keen to include members in all activities, but they should be proactive in getting involved: “Things don’t just happen, they have to be made to be happen. You are at the stage in your careers when you have to make things happen.”

He said members should join the Sections to build expertise, get involved with the Research Foundation, submit to the three EAU journals, work on ESU courses, and contribute to the Guidelines and Patient Information groups. He stressed the importance of networking, evidence-based rather than eminencebased medicine, and embracing the whole field in order to maintain control as a urologist rather than becoming a technician.

“At the end of the day, the future is in your hands,” Chapple said, “Look on the website for grants, activities, how to get involved, and help the EAU achieve its mission statement.”

Dr. Panagiotis Kallidonis (GR) said it was difficult to report on all of the YAU non-oncology working groups’ achievements over the past 12 months into a ten-minute presentation, but managed to show that the Functional, Men’s Health, Paediatrics, Trauma & Reconstructive, and Endourology-Lithiasis groups all made robust contributions to the peer-reviewed literature, academic meetings, educational courses, and ongoing research. “There is a lot of work being done in these groups. All of these people are going to develop themselves and provide something better for our specialty.”

• Best paper published in 2017 by the Prostate Cancer YAU group – Dr. Roderick Van den Bergh (NL) • Best poster presented at EAU 2018 by the Mens Health YAU group – Dr. Giorgio Ivan Russo (IT) • Reviewer of the year from YAU – Dr. Andrea Necchi – collected by Prof. Evangelos Liatsikos (GR) on behalf of winner

Dr. Guillaume Ploussard (FR) said that the technology (UroTechnology and Robotics) and oncology (Bladder, Renal and Prostate) working groups had been similarly successful in the same areas, “Last year was very good for these groups. I am sure 2018 will be even better.”

The following YAU awards were presented by Prof.

Hein Van Poppel (BE):

Dr. Sedelaar and Prof. Silay chairing the meeting of the Young Academic Urologists.

Award Gallery Congress news. . . . . . . . . . . . . . . . . . . . . . . . 1 Congress highlights . . . . . . . . . . . . . . . . . . 2/3 What does the urologist need to know about EDCs. . . . . . . . . . . . . . . . . . . . . . . . . . . 5 Complications after open radical cystectomy . 6 C. Chapple awards V. Mirone with the EAU Willy Gregoir Medal

D. Jacqmin receives the EAU Frans Debruyne Life Time Achievement Award from C. Chapple

S. Musitelli receives the EAU Ernest Desnos Prize from C. Chapple

Novel antibiotics in treating Urinary Tract Infections. . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 Novel modalities for nodal staging in prostate cancer. . . . . . . . . . . . . . . . . . . . . . . . 8 Precision medicine in bladder cancer. . . . . . . 9 Infectious complications and fURS. . . . . . . . . 11 Ernest Desnos: Honouring urology historians.12 EAU Guidelines: Ensuring consistent European urological care. . . . . . . . . . . . . . . 13 Update in vaginoplasty technique. . . . . . . . . 14

S. Silay receives the EAU Crystal Matula Award from C. Chapple and M. Frazzette from LABORIE

D. Dalela accepts the EAU Hans Marberger Award from C. Chapple and E. Dourver from KARL STORZ

H. Ahmed accepts the EAU Prostate Cancer Research Award from C. Chapple and F. Schröder from the FHS FOUNDATION

Managing complex cases in functional urology. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15 Residual fragments - an ongoing headache after fURS. . . . . . . . . . . . . . . . . . . 16 Is TURP safe in frail elderly men or is MIT better?. . . . . . . . . . . . . . . . . . . . . . . . . . 18 My journey in prosthetic urology . . . . . . . . . 19 Oncological outcomes following robotic-assisted RC. . . . . . . . . . . . . . . . . . . . 20 Antibiotic treatment’s collateral effects. . . . . 22

C. Chapple congratulates G. Aus with his EAU Honorary Membership

C. Chapple congratulates P. Coloby with his EAU Honorary Membership

C. Chapple congratulates M. Menon with his EAU Honorary Membership

Office Urology: Meeting the challenges. . . . . 23 Introducing European Urology Oncology . . . . 24 Predicting resistance to BCG therapy . . . . . . 25 Robotic radical cystectomy. . . . . . . . . . . . . . 26 Best Abstracts: First prize winners. . . . . . . . 28 ESU Masterclasses: Designed and aimed to educate. . . . . . . . . . . . . . . . . . . . . 29 Low-intensity ESWT . . . . . . . . . . . . . . . . . . . 30

Prof. C. Chapple congratulates A. Vaze with his EAU Honorary Membership

Saturday, 17 March 2018

If you want to find out more about our upcoming meetings and projects, please visit the EAU Wall in the Green Area.

Shared decision-making in prostate cancer care. . . . . . . . . . . . . . . . . . . . . . . . . . 31

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Through numerous industry collaborations, we seek to explore the potential synergies of combining our immunotherapies with other immune-modulators.

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Saturday, 17 March 2018

What does the urologist need to know about EDCs? Multi-sectoral action is needed to reduce and eliminate Endocrine Disrupting Chemicals intra-uterine exposure to pseudo-estrogens and anti-androgens. Recently, it was shown that the use of paracetamol during pregnancy doubles the risk of cryptorchidism. Other exposures possibly involved in male maldevelopments are air pollutions (diesel), maternal and paternal smoking. Children born after IVF have an increased risk of hypospadias.

Prof. Gert R. Dohle Erasmus MC Rotterdam Rotterdam (NL)

Endocrine disrupting chemicals (EDCs) influence our health, including male genital development and male reproduction. There is an increase in most western societies in male reproductive disorders: the most striking ones are the decline in sperm quality and the increase in testicular cancer.

In animal studies different industrial chemicals have been shown to cause maldevelopment of the male genitalia. These chemicals have a similar structure to estrogens and are also named pseudo-estrogens or xeno-estrogens. They can easily pass the placenta and act as estrogen, disrupting testicular development.

Other chemical compounds have an anti-androgenic action in the male fetus. EDCs are common in our daily environment and are used in many products, including plastics, flame retardants, cosmetics and pesticides.

These problems arise from a maldevelopment of the testes during early pregnancy, also known as testicular dysgenesis syndrome (TDS). Both in wildlife observations and in animal experiments TDS develops after exposure to EDCs, resulting in abnormal genital development, a short anogenital distance and infertility. Data from ongoing longitudinal studies in children confirm that our western lifestyle is a major contributing factor in the etiology of male genital development disorders.

The number of diseases potentially linked to early life EDCs exposure is substantial and include; 1) obesity and diabetes.

2) female reproduction (premature ovarian failure, female infertility).

3) male reproduction (cryptorchidism, hypospadias, male infertility, male hypogonadism).

4) hormone-sensitive cancers in males and females (breast cancer, testicular cancer, ovary tumors, thyroid cancer).

Male genital development 5) neurodevelopment and neuroendocrine systems The male genitalia develop between week 7 and week disorders (ADHD, Autism).

14 of pregnancy. The activity of the sex region of the Y 6) Immune system defects (asthma, food allergies). chromosome (SRY gene complex) results in differentiation of the fetal gonad into a fetal testis.

Many of these diseases will only appear later in life, Already early in pregnancy the fetal testis starts thus making it difficult to prove a causal relation with producing hormones, like testosterone, antiprenatal EDCs exposure. However, in the last years Muellerian hormone (AMH) and Insl-3 (Figure 1). both animal and human studies have strongly Testosterone plays a central role in the further indicated this relationship. Animal studies and differentiation of the male genitalia, either direct observation in wildlife provide strong evidence that (development of the epididymis and vas deferens) or manmade chemicals can disrupt the hormone after conversion into dihydrotestosterone (DHT, dependent pathways responsible genital development of the external genitalia and prostate). development.

Male under-virilization can be caused by different defects in this system, including low fetal testosterone Consequences of TDS in adult life production, absence of 5α-reductase and malfunction A decline in sperm quality has recently been of the androgen receptor. confirmed by a large meta-analyses of more than 5,000 publications: the authors found a 50–60% Maldevelopment of the fetal testes and low fetal decline in sperm counts among men unselected by testosterone production can result in birth defects, fertility from North America, Europe, Australia and like cryptorchidism and hypospadias. Later in life New Zealand, without signs of “leveling off” in more these men will have small testes, low testosterone recent years (Levine et.al.). A recent study from China production (congenital hypogonadism), defective in more than 30,000 young man found a decline in spermatogenesis and an increased risk for testicular sperm concentration of 35% in a 15-year study period. cancer (Figure 2).

Studies in humans now also show a negative effect of Epidemiology and etiology of TDS EDCs on male fertility: in a recent study the effects of The incidence of cryptorchidism and hypospadias is pesticides exposure in early life resulted in a decline rising in some western countries. Both conditions of sperm quality of 30% later in life compared to men have mixed etiology, including genetic factors and that were not exposed. In the same period, we have

observed an significant increase in the incidence of testicular cancer (TC) in western countries. In the Netherlands, as in most other European countries, the incidence of testicular cancer has more than doubled in the last two decades. Although prognosis is good in terms of disease survival, many of these men will be hypogonadal after treatment. Infertility is high in these men: at time of diagnosis 50% of these men have low sperm quality and 12% are azoospermic.

At Erasmus MC we have shown that the origin of testicular cancer occurs during fetal life. TC arises from embryonic germ cells that have failed to mature appropriately. These precursor cells of TC are known as carcinoma in situ (GNCIS). Only after puberty, when testosterone levels increase, TC will develop. Multiple genes that play a role in embryonic development of the testes are also involved in the developments of carcinoma in situ of the testes: OCT3/4, SRY, SOX2, SOX17, KIT-ligand.

Novel insights indicate a subtle interplay of specific single nucleotide polymorphisms (SNPs), environmental factors, and epigenetic aberrations in the etiology of germ cell cancers.

Late consequences of TDS Male infertility and primary hypogonadism are related to health problems later in life. These men have an increased risk for obesity, type 2 diabetes mellitus, cardiovascular disease and depression.

Men with azoospermia have a 2.2 fold increased risk of developing cancer later in life, including germ cell cancers, prostate cancer and lymphomas. Poor semen quality and low testosterone are biomarkers for future health problems. Life expectancy is shorter in these men.

Action needed against EDCs The World Health Organization and the Endocrine Society have urged policymakers to take measures against EDCs. The estimated costs of inaction against the effects of EDCs of male health in Europe are estimated to be 592 million euros per year (Nordic Council report 2014). Well-designed studies are needed to show how EDCs exposures in early life are the basis of many diseases later in life.

The Health commission of the EU has invited research groups to initiate further investigations and 50 million euros are made available within the program Horizon 2020 for this type of studies. However, more action is needed: we need to reduce and eliminate those EDCs that have already been shown to be harmful for human health (Bisphenol A, DEHP, flame retardants, parabens, PCBs). Hundreds of manmade substances in our daily environment have been indicated to act as EDCs. Furthermore, public awareness needs to be improved, such as explaining to pregnant women and young mothers how to limit and avoid exposures to EDCs. Campaigns have already been launched: www.

wecf.org. Special attention is focused on alternatives for pesticides and plastics.

Key points 1. Testosterone is essential for normal male development; 2. Testicular maldevelopment can result in cryptorchidism, hypospadias, male infertility and testicular cancer: testicular dysgenesis syndrome (TDS) is the common links between these diseases; 3. Genetic abnormalities, life style factors and endocrine disrupting chemicals (EDCs) are the main causes of TDS; 4. Male infertility and congenital male hypogonadism are associated with obesity, type 2 diabetes mellitus and cardiovascular diseases; 5. Endocrine related cancers have increased substantially in the last decades, including testicular cancer, breast cancer, prostate cancer and thyroid cancer; and 6. Public awareness campaigns are needed to protect especially pregnant woman and young children against the harmful effects of EDCs. References 1. G.R. Dohle, S. Arver, C. Bettocchi, T.H. Jones, S. Kliesch,.

European Association of urology guidelines on male hypogonadism. Update 2018. Uroweb.org/guidelines 2. Skakkebaek NS, Rajpert-De Meyts E, Main KM. Testicular dysgenesis syndrome: an increasingly common developmental disorder with environmental aspects.

Hum Reprod 2001; 16: 972-78.

3. Gore AC, Chappell VA, Fenton SE, et. al. The Endocrine Society’s Second Scientific Statement on EndocrineDisrupting Chemicals. Endocr Rev. 2015 Dec;36(6): E1-E150.

4. Levine H, Jørgensen N, Martino-Andrade A, Mendiola J, Weksler-Derri D, Mindlis I, Pinotti R, Swan SH. Temporal trends in sperm count: a systematic review and meta-regression analysis. Hum Reprod Update. 2017 1;23(6):646-659.

5. van der Zwan YG, Biermann K, Wolffenbuttel KP, Cools M, Looijenga LH. Gonadal maldevelopment as risk factor for germ cell cancer: towards a clinical decision model.

Eur Urol. 2015;67(4):692-701.

6. Eisenberg ML, Li S, Cullen MR, Baker LC. Increased risk of incident chronic medical conditions in infertile men: analysis of United States claims data. Fertil Steril.

2016;105(3):629-636.

7. Latif T, Kold Jensen T, Mehlsen J, Holmboe SA, Brinth L, Pors K, Skouby SO, Jørgensen N, Lindahl-Jacobsen R. Semen Quality as a Predictor of Subsequent Morbidity: A Danish Cohort Study of 4,712 Men With Long-Term Follow-up. Am J Epidemiol. 2017 15;186(8):910-917.

Saturday, 17 March 08.15- 10.00: Plenary Session 1. Hot topics, evidence quality and advances in andrology

Figure 1.: Fetal development of the male genitalia

Figure 2. Adapted from: N.E. Skakkebaek et. al. Hum Reprod 2001: 16: 972-78.

Fetal pituitary LH H Leydig cells

FSH HH Fetal testis

Testosterone e

INSL3

SRY gene complex

Dihydrotestosterone (DHT) Differentiation of the genital tubercle and the urogenital sinus External genitalia Prostate

Figure 1.: Fetal development of the male genitalia

Saturday, 17 March 2018

SRY gene complex, SOX genes

Sertoli cells

Anti-Müllerian hormone (AMH) Regression of the Müllerian ducts

Epididymis Vas deferens

Genetic defects

Endocrine disrupting chemicals (EDCS)

5α-reductase

Differentiation of the Wolffian ducts

Environmental and life style factors

Testicular dysgenesis syndrome (TDS)

Sertoli cell dysfunction

Leydig cell dysfunction

Impaired germ cell differentiation

Androgen deficiency

Testicular descent Male infertility

Hypospadias

Testicular Tumors

Cryptorchidism Congenital hypogonadism

Figure 2. Adapted from: N.E. Skakkebaek et. al. Hum Reprod 2001: 16: 972-78.

EUT Congress News

5

Complications after open radical cystectomy Open RC remains most effective treatment despite complications risks Prof. Georgios Gakis Department of Urology and Pediatric Urology Julius-Maximillians University of Würzburg Würzburg (DE)

correlation was reported between pelvic venous pressure and central venous pressure3. Continuous norepinephrine administration resulted in lower blood loss and rate of transfusions4. Moreover, in patients with neobladder, restrictive intraoperative fluid management was associated with improved continence and potency results postoperatively5.

Venous thromboembolism (VTE) Postoperative venous thromboembolism (VTE) occurs in 2.5-10% of all patients undergoing radical cystectomy for bladder cancer9-11. The wide range in reported rates is possibly related to an under-reporting bias across different countries which, in turn, is likely due to under-registration of thromboemblic events after discharge in different health care systems. It is important to note that the majority of thromboembolic events occur after discharge of the patient10.

improved perioperative gastrointestinal (GI) recovery and lower rates of GI complications16,17.

In some studies additional benefits were reported with the adoption of ERAS protocols resulting in shorter time intervals on intensive care units, lower rates of wound healing disorders and VTE events18.

Moreover, a randomized study revealed that total parenteral nutrition for the first five days after surgery resulted in higher number of postoperative complications which was mainly due to a higher rate of infectious complications19.

Pulmonary complications The occurence of pulmonary complications is often associated with patient risk factors. Approximately 6% of patients develop postoperative pulmonary Risk factors for the development of VTE include a high Complications during or after radical cystectomy are complications after cystectomy. Risk factors for BMI, positive surgical margins, type of urinary frequent with delayed diagnosis and treatment postoperative pulmonary complications were reported diversion and prolonged duration of hospitalization10 Summary resulting in severe chronic morbidity. Therefore, its to be higher age (75 years and older), very low (<18.5) and non-O blood type11. Of the thromboembolic events Given the tumor aggressiveness of muscle-invasive management requires a high level of knowledge and or very high (>=30) body mass index (BMI), smoking, 40% of cases relate to deep vein thrombosis and 60% bladder cancer open radical cystectomy is nowadays experience as this surgical procedure may cause chronic obstructive pulmonary disease, insulinto pulmonary embolism10. In various studies it was still the most effective treatment option for the severe morbidity in fourth of the patients with treated diabetes and low albulin levels (<3.5g/dL)6. consistently reported that extended duration of treatment of muscle-invasive bladder cancer. The mortality rates rapidly increasing with complications1. Therefore, some efforts have been undertaken to thromboprophylaxis using low-molecular weight increasing use of neodjuvant and adjuvant treatment This article summarizes recent studies with high level reduce the risk of pulmonary complications heparin derivates for four weeks after discharge modalities mandates further attempts to reduce the of evidence in this field. postoperatively. One strategy that has been rate and severity of perioperative complications. reduces the relative risk of VTE by approximately investigated was to compare the rate of complications 70%12 while the risk of delayed bleeding during Intraoperative blood loss using either a low vs. high positive end-exspiratory extended treatment is low13. Importantly, a recent In recent years an increasing number of randomized Open radical cystectomy is still the mainstay of pressure and alveolar recruitment manoeuvres during study also revealed that thromboembolic events are trials have addressed critical issues of perioperative treatment for muscle-invasive bladder cancer1. surgery. Looking into the literature there is divergent care. Further well-designed trials are warranted in more frequent in patients receiving neoadjuvant data on whether this anesthesiologic strategy during It has been consistently reported that open radical this major urological field of surgery to improve our chemotherapy for muscle-invasive bladder cancer surgery may have beneficial effects on pulmonary cystectomy, as a major surgical procedure, is understanding in refinements of perioperative care (17%) supporting the use of agents for function postoperatively. associated with a higher estimated blood loss for improved functional and oncological outcomes thromboembolic prophylaxis during chemotherapy14. during surgery compared to robotic cystectomy2. after cystectomy.

In the largest study, Hemmes et al. did not find a Therefore, reducing blood loss has come to the Gastrointestinal complications significant impact of this manoeuvre on outcomes focus of surgeons experienced in open Editorial Note: Due to space constraints, the The construction of urinary diversion is the main after major abdomimal surgery. On the contrary, techniques. reference list can be made available to interested reason for postoperative complications after a trend towards improved outcomes was noted readers upon request by sending an email to: cystectomy. A lot of discussion currently focuses on Easy and intuitive PDD in Precision Modularity Flexibility S-Technologies Ergonomic Easy and intuitive PDD in Precision Modularity Flexibility when a strategy with low tidal volume and low In a double-blind trial randomized trial, the type of diversion in octogenarians, most of which communications@uroweb.org S-Technologies Ergonomic Easy and intuitive PDD in Precision Modularity Flexibility S-Technologies Ergonomic Easy and intuitive PDD in Precision positive end-exspirary pressure without intraoperative blood loss was lower in patients often suffer from severe comorbities prior to surgery.

Modularity Flexibility S-Technologies Ergonomic Easy and intuitive PDD in Precision Modularity Flexibility S-Technologies Ergonomic Easy and intuiti7 recruitment manoeuvres was used . In a with pelvic venous pressure less than 5 mm Hg. Saturday 17 March In this regard, avoiding the use of intestinal segments ve PDD in Precision Modularity Flexibility S-Technologies Ergonomic Easy and intuitive PDD in Precision Modularity Flexibility S-Technologies Ergometa-analysis, low tidal volume was also Low pelvic venous pressures were also more 10.15-15.30: Joint meeting of the EAU Section of for reconstruction of the urinary route using, i.e. a nomic Easy and intuitive in Precision Modularity Flexibility S-Technologies Ergonomic Easy and intuitive PDD in Urology Precision reported to be most protective against the frequent in patients treated with PDD a Oncological (ESOU), Modularity the EAU Robotic Flexibility ureterocutaneostomy, was shown to significantly S-Technologies Ergonomic PDD in Precision Modularityreduce Flexibility Ergonomic Easy and intuitive Flexibility S-Techdevelopment of postoperative acute respiratory norepinephrine-low-volume strategyEasy and intuitive Urology Section (ERUS), the EAU Section of the rate of S-Technologies major complications (11% vs.

25%) 8 ologies Ergonomic Easy and intuitive PDD in Precision Modularity Flexibility S-Technologies Ergonomic Easy and intuitive PDD in Precision MODULAdistress syndrome . The most widely accepted intraoperatively as compared to liberal use of Uro-Technology (ESUT) and with the ESSO, and 30-/90 mortality rates (5.9%/6.9% vs.

15 RITYintravenous Flexibility andduring intuitive PDD in Precision Flexibility S-Technologies Ergonomic practiceEasy for ventilation radical cystectomy fluid. S-Technologies Furthermore, pelvic venousErgonomic . In ESTRO, EUOG, EORTC GUCG andEasy SUO; and intuitive 7.7%/17.3%)Modularity in patients aged 75 years and older PDD pressure in Precision Modularity Easy and intuitive Ergonomic Modularity Flexibility S-Technologies Easy and intuitive in Precision Mois nowadays to avoid high end-exspiratory decreased significantly after removing this regard, protocols for enhanced Ergonomic recovery after Complications in treatmentPDD of urological dularityabdominal Flexibility S-Technologies Easy and intuitive PDD in Precision Flexibility Modularity S-Technologies Ergonomic PDD in pressures and high tidal volumes during surgery packing and abdominal lifting at all Ergonomic surgery have nowadays been adopted in clinical Flexibility cancers Precision Flexibility Ergonomic Easy and intuitive Flexibility S-Technologies Ergonomic Easy and intuitive PDD in whenever possible. time pointsModularity during cystectomy.

Of note, no S-Technologies practice HD and found to be associated with significantly

TP 61 2.0 02/2018/A-E

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6

EUT Congress News

Saturday, 17 March 2018

Novel antibiotics in treating Urinary Tract Infections Antimicrobial stewardship is crucial to maintain efficacy of current antibiotic agents Assoc. Prof. Kurt G. Naber Department of Urology Technical University of Munich Munich (DE)

Co-Author: Florian M.E. Wagenlehner, Clinic for Urology, Pediatric Urology and Andrology, Justus Liebig University, Giessen (DE) Antibiotic resistance in Gram-negative uropathogens is increasing worldwide. A compilation of worldwide studies showed resistance rates of Gram-negative uropathogens against fluoroquinolones in 10 to 80%, against cephalosporines in 5 to 70% and against carbapenems in 0 to 35%1.

ceftazidime/avibactam vs doripenem was demonstrated for the FDA co-primary endpoints (symptomatic resolution/microbiological eradication at test of cure (TOC): 280 of 393 (71.2%) vs 269 of 417 (64.5%) patients (difference, 6.7% [95%CI, 0.3% to 13.1%]).

Microbiological eradication at TOC occurred in 304 of 393 (77.4%) ceftazidime/avibactam vs 296 of 417 (71.0%) doripenem patients (difference, 6.4% [95% CI, 0.3% to 12.4%]), demonstrating superiority at the 5% significance level. Both treatments showed similar efficacy against ceftazidimenonsusceptible pathogens. Ceftazidime/avibactam had a safety profile consistent with that of ceftazidime alone. Thus, ceftazidime-avibactam was highly effective for the empiric treatment of cUTI/ APN and may offer an alternative to carbapenems in this setting8.

Figure 1: Global and regional resistance rates of uropathogens (total spectrum) in health-care associated urinary tract infections (HAUTI)2

eradication, clinical, and composite (microbiological and clinical) cure rates at the end-of-IV therapy (EOIV) and TOC (Day 15-19) in mMITT population were 3. Meropenem / Vaborbactam analyzed for cUTI and APN subgroups. At TOC, PLZ Vaborbactam is a novel cyclic boronic acid inhibitor of achieved higher composite cure rates than many class A and class C enzymes. It is a potent meropenem in cUTI (84/107=78.5% vs. 82/119=68.9%; inhibitor of serine carbapenemases, and KPC in difference 9.6 (95%CI; -2.6 to 21.3) and APN A specific surveillance study in urology is the Global 5. Cefiderocol Prevalence of Infections in Urology (GPIU), which is a particular. In-vitro data suggest that meropenem(72/84=85.7% vs. 56/78=71.8%; difference 13.9 Cefiderocol (S-649266) is a novel parenteral vaborbactam (M-V) is highly active against KPCworldwide point prevalence study performed every siderophore cephalosporin conjugated with a catechol (95%CI;0.4 to 27.1), driven by higher microbiological eradication rates in each subgroup. The incidence of November since 2003. This study is intended to create producing Enterobacteriaceae. Little effect on A. moiety at the third-position side chain. Cefiderocol baumannii containing OXA-type carbapenemases was utilizes a novel mechanism of entry into the surveillance data in patients at urological AEs, including SAEs and AEs leading to discontinuation of IV study drug, was low and departments with health-care associated urinary tract observed7,9. periplasmic space of Gram-negative bacteria and is infections (HAUTI)2. Resistance rates of most comparable between treatment arms20. broadly stable to ESBLs and carbapenemases. The in uropathogens against all tested antibiotics were high, A phase-3 study (TANGO-1) evaluated the efficacy, vitro activity of cefiderocol against Pseudomonas safety, and tolerability of M-V (Vabomere®) compared aeruginosa was enhanced under iron-depleted particularly with regards multidrug resistance 7. Finafloxacin (Figure 1). In many countries the resistance rate of to piperacillin/tazobactam (P-T) in the treatment of Finafloxacin, an investigational fluoroquinolone, conditions, whereas that of ceftazidime was not Gram-negative uropathogens only against cUTI/APN in adults. M-V (meropenem 2 g plus suitable for IV and oral administration, is being affected. Cefiderocol was shown to have potent carbapenems is below 10%, a threshold used for vaborbactam 2 g), administered IV q8h vs P-T developed as sequential therapy of bacterial chelating activity with ferric iron, and extracellular empiric therapy of severe infections, such as infections including UTIs. The compound exhibits (piperacillin 4 g plus tazobactam 0.5 g), q8h. After a iron was efficiently transported into P. aeruginosa urosepsis. A worrying finding in the GPIU study was minimum of 15 IV doses LVX 500mg could be good activity against Gram-positive, Gram-negative cells in the presence of cefiderocol as well as also that the severity of HAUTI is also increasing, 25% administered orally q24h, if clinically indicated. Total and anaerobic pathogens with a bactericidal siderophores. Cefiderocol forms a chelating complex being urosepsis in recent years. treatment was 10 days, unless a participant had mechanism of action, a high level of excretion in the with iron, which is actively transported into P. baseline bacteremia where up to 14 days of therapy urine and increased potency at acidic pH21. aeruginosa cells via iron transporters, resulting in Need for novel antibiotics could be administered IV. (https://clinicaltrials.gov/ potent antibacterial activity of cefiderocol against P. Although for uncomplicated cystitis old antibiotics, ct2/show/NCT02166476).

In a phase-2 trial finafloxacin (IV and oral) was aeruginosa14. such as fosfomycin trometamol, nitrofurantoin, examined for a total of five days (FINA05) or 10 days pivecillinam, and nitroxoline are still recommended Of 550 subjects randomized, 374(68.0%) included In total, 189 non-fermentative Gram-negative bacteria (FINA10) versus ciprofloxacin (IV and oral) for 10 days as first-line3,4, for complicated and especially HAUTI in m-MITT (165/192[85.9%] in M-V and (107 Acinetobacter baumannii and 82 Pseudomonas (CIPRO10) for the treatment of cUTI/APN. Patients novel antibiotics need to be developed. Several 154/182[84.6%] in P-T groups had baseline were randomized 1:1:1 into one of the three treatment aeruginosa ) and 282 Enterobacteriaceae were strategies are currently employed in the development Enterobactericeae. Mean duration of IV therapy was studied. Cefiderocol exhibited greater antimicrobial arms. The study lasted 24±2 days with examinations of novel antibiotics: Beta-lactam/Beta-lactamase eight days. At the end of IV treatment clinical cure activity in vitro against carbapenem-resistant on Day 3, on 10±2 and 17±2 days (TOC). inhibitor combinations are extended to was observed with M-V in 162/165=98.2% and with Gram-negative bacteria than several comparator cephalosporins and also carbapenems. So called P-T in 147/154=95.5% of the patients. antibiotics15.

The treatment success (combined clinical and siderophore antibiotics (beta-lactams) are tested.

Microbiological eradication was found in microbiological response) for the m-ITT population 161/165=97.6% with M-V and 142/154=92.2% with Novel aminoglycosides, novel fluoroquinolones and In a phase-2 study efficacy and safety of IV TOC was 70.3%(95%CI: 57.6%-81.1%) in the FINA05 novel tetracyclines are also in clinical development.

P-T. Clinical outcomes were >90% across all MICs. cefiderocol versus IV IMP/CS was tested in group, 67.6%(55.2 78.5%) in the FINA10 group and hospitalized adults with cUTI/APN. Patients with 57.4%(44.1%-70.0%) in the CIPRO10 group.

1. Ceftolozane / Tazobactam Although 19.5% of baseline Enterobacteriaceae Gram-negative pathogens were randomized 2:1 to Finafloxacin dosed for five or 10 days showed higher Ceftolozane/tazobactam is a novel cephalosporin isolates were non-susceptible to P-T, clinical and receive cefiderocol(2 g) IV q8h, or high-dose IMP/ treatment success rates than ciprofloxacin dosed for 10 days. The microbiological eradication rate of combined with an established beta-lactamase inhibitor microbiologic outcomes were similar for subjects with CS (1g/1 g) IV q8h, for seven to 14 days. Of the 452 patients randomized, 448 were treated and 371 of ciprofloxacin was lower in patients with acidic (BLI). This drug has in-vitro activity against multidrug- susceptible and non-susceptible isolates10. The most urine- pH as compared to those with alkaline resistant strains of Pseudomonas aeruginosa and other common adverse reactions in patients taking M-V the micro-ITT population were assessed for common Gram-negative pathogens, including most efficacy. urine-pH, while finafloxacin’s microbiological were headache, infusion site reactions and diarrhea.

ESBL-producing Enterobacteriaceae spp. eradication rate was equally high at either pH range M-V is associated with serious risks including allergic on Day 3. The safety profiles of the three treatment Cefiderocol met the FDA primary efficacy endpoint of reactions and seizures11. groups were equivalent and the majority of the AEs composite of clinical cure and microbiologic In a phase-3 study ceftolozane/tazobactam was compared with levofloxacin (LVX) in hospitalized TANGO-2 trial including also cUTI/APN caused by eradication at TOC in 72.6% of patients(n=252) which were mild to moderate in severity and regarded to be unrelated to study medication21. patients with complicated UTI (cUTI) or acute carbapenem-resistant Enterobacteriaceae (CRE) was superior to IMP/CS at 54.6%(n=119), difference pyelonephritis (APN). Patients were randomly stopped early for superior benefit-risk with M-V 18.58% (95%CI: 8.23, 28.92). Cefiderocol was well tolerated; 40% of patients experienced an adverse assigned 1:1 to receive 1.5g intravenous (IV) compared to best available therapy for CRE12.

8. Eravacycline event (AE) with cefiderocol vs 50% of patients with ceftolozane-tazobactam q8 h or 750mg IV LVX qd, Eravacycline is a novel synthetic fluorocycline that is IMP/CS. Serious adverse events (SAEs) occurred in 14 both for seven days. Of 1083 patients enrolled, 4. Imipenem /Relebactam active against most Gram-negative species. In vitro 800(73.9%), of whom 656(82.0%) had APN, were Relebactam is a non-beta-lactam serine BLI, similar patients (4.7%) who received cefiderocol and 12 eravacycline is two- to four-fold more potent than included in the m-MITT population. Ceftolozane/ to avibactam, that has inhibitory activity against class patients (8.1%) who received IMP/CS16. tigecycline against CRE7. tazobactam was non-inferior to LVX for composite A and C beta-lactamases. In vitro assays with (microbiological/clinical) cure (306[76.9%] of 398 carbapenem-resistant Enterobacteriaceae isolates 6. Plazomicin A phase-3 study evaluating eravacycline 1.5mg/kg vs. 275[68.4%] of 402, 95%CI 2,3-14.6) and, as the demonstrated that MICs were significantly lowered Plazomicin (PLZ) is a novel aminoglycoside that was versus 750mg LVX for the treatment of cUTI/APN lower bound of the 95%CI was >0, superiority was when imipenem(IMP) was tested with relebactam synthetically derived from sisomicin. Like other (IGNITE2) with an oral step-down did not achieve indicated. Adverse event profiles were similar in against KPC-producing K. pneumoniae. Compared to aminoglycosides, it is a bactericidal agent that works non-inferiority. These data remain unpublished to the two treatment groups and were mainly IMP alone, little reduction in imipenem-relebactam primarily through inhibition of protein synthesis. PLZ date and thus further studies are needed to establish non-serious. Thus, ceftolozane/tazobactam led to MICs were noted in OXA-48-producing K. is structurally similar to the traditional the role of eravacycline in treating CRE7. better responses than high-dose LVX in patients pneumoniae or OXA-23-producing A. baumannii, aminoglycosides (amikacin, gentamicin, tobramycin), with cUTI/APN5. suggesting that relebactam, unlike avibactam, does though was modified to resist aminoglycosideCrucial role of antimicrobial stewardship not have significant activity against the class D modifying enzymes that are often present in CRE. PLZ Several antibiotic substances are currently upon 2. Ceftazidim /Avibactam enzymes7,9. Phase 2 clinical trials investigating the is not affected by carbapenemase production and has marketing, or in the late clinical phase of Avibactam, a non–beta-lactam BLI, restores the safety, tolerability, and efficacy of IMP/CS-relebactam good in-vitro activity against carbapenem-resistant development. Nevertheless, unique novel substances activity of ceftazidime against Ambler class A (eg,ESBL in treating complicated urinary tract infections and isolates of K. pneumoniae, E. coli, and Enterobacter are rare, therefore antimicrobial stewardship plays an and KPC), class C (eg, AmpC), and some class D complicated intra-abdominal infections have been species producing a variety of carbapenemases and important role to preserve the antibiotic substances ESBLs. The presence of 16S rRNA methyltransferase in available. beta-lactamase–producing bacteria. It is not active completed13.

Enterobacteriaceae, which modifies the ribosomal site against metallo-beta-lactamases6,7. that binds PLZ, leads to plazomicin resistance. PLZ is A phase-3 trial (RESTORE-IMI-1) is underway Editorial Note: Due to space constraints the reference RECAPTURE 1 and 2 comprised two identical phase-3 investigating efficacy and safety of IMP/CS + more potent than other aminoglycosides in treating list has been omitted. Interested readers can email at studies in patients with cUTI/APN. Eligible patients relebactam vs colistin + IMP/CS for cUTI/APN due to Enterobacteriaceae7,17,18.

EUT@uroweb.org for a complete listing. were randomized 1:1 to IV ceftazidime-avibactam IMP-resistant pathogens. Group 1: IMP/CS 2000 mg/500 mg every 8 hours or IV doripenem 500 relebactam IV (200mg/100mg to 500mg/250mg A phase-2 study was performed in patients with cUTI/ Saturday 17 March mg every eight hours. Of 1033 randomized patients, depending on renal function) q6h and placebo APN compared PLZ with LVX19. In a phase-3 study 10.00-14.00: Joint meeting of the EAU Section 393 and 417 treated with IV ceftazidime/avibactam colistimethate sodium (CMS) IV q12h. Group 2: CMS (EPIC) hospitalized patients with cUTI/APN received IV of Andrological Urology (ESAU) and the EAU and IV doripenem, respectively, were eligible for the [colistimethate base activity (CBA) 300mg] IV loading PLZ (15mg/kg q24h) or IV meropenem (1g q8h) for Section of Infections in Urology (ESIU); When primary efficacy analyses; 19.6% had ceftazidimedose, followed by CBA 75mg to 150mg) IV q12h and four to seven days, followed by optional oral therapy, basic science meets clinical practice nonsusceptible baseline pathogens. Non-inferiority of IMP/CS (200mg to 500mg) IV infusion q6h. Group 3: for a total of seven to 10 days. Microbiological Saturday, 17 March 2018

participants with IMP- and colistin-resistant pathogens received open-label IMP/CS - relebactam (200mg/100mg to 500mg/250mg) IV q6h. Treatment duration: five to 21 days. (https://clinicaltrials.gov/ct2/ show/NCT02452047).

EUT Congress News

7

Novel modalities for nodal staging in prostate cancer Burden of nodal disease is linked with poorer outcomes Dr. Henk van der Poel Dept. of Urology Netherlands Cancer Institute Amsterdam (NL)

Moreover, molecular staging by RT-PCR showed nodal metastases in up to 30% of men with routinelyassessed node negative disease and these men were at risk of disease recurrence13,14. On the other hand, 68Ga-PSMA-PET scanning had high accuracy in detecting non-local recurrences after radical prostatectomy8 even at PSA levels below 0.5 ng/ml.

This indicates that PSMA-PET scanning may help to select men for salvage local radiotherapy after prostatectomy9,10.

In prostate cancer, nodal metastases are an initial step in the development of distant disease in the vast majority of men. Moreover, disease recurrence after local therapy is most frequently caused by the presence of nodal metastases. These observations supported the notion that nodal metastases do develop early in the progression process of prostate cancer.

Surgery From surgical studies on lymph node dissection we already know that the removal of more nodes during an (extended) lymph node dissection results in a higher yield of nodal metastases and potentially longer biochemical recurrence-free survival1,11. Even though an extended dissection of nodal tissue may result in better outcome when compared to no or limited dissection, still the addition of adjuvant radiotherapy and androgen ablation further improved outcome1.

Nodal metastases and survival Still the precise moment of nodal metastases development remains illusive. Yet, understanding how and when nodal disease develops is crucial in understanding cancer progression and determining timing of treatment as opposed to active surveillance.

Prognosis of men with nodal metastases-only is far better than that for men with metastases to other sites and the majority of men are alive 10 years after diagnosis15,19. Moreover, recent analyses suggested a survival benefit of early nodal metastases treatment1,2.

The number of removed nodes as well as the number of nodes containing metastases is predictive of survival outcome15,19,20.

These observations from retrospective series seem to support two notions: a. that imaging of all relevant nodal metastases is not feasible with current imaging modalities; b. that complete ablation of nodal metastases will require more than removing visible metastases only. Considering these observations it can be assumed that, although imaging may direct treatment to specific nodal zones where metastases are most likely, better predictors of nodal metastases are needed to fully eradicate remnant disease. The same seems to apply to the use of radio-guided-PSMA tracer directed surgery as recently very elegantly introduced by the group of Tobias Maurer12.

Imaging In prostate cancer, nodal metastases conventional imaging has long been limited due to its inadequacy to detect pelvic nodal lesions smaller than 7-8mm.

Therefore, current guidelines do not recommend imaging for nodal staging in localized prostate cancer3.

Although interesting to guide towards nodes most likely to contain metastases, this method still will leave untreated the nodal metastases which are under the detection threshold. A nodal-template directed treatment rather than targeting visible nodal metastases could improve outcome. This would not only apply to men with macroscopic nodal metastases but might also improve outcome in men with microscopic or molecular metastases where a benefit may even be higher as implied by the observation that men with less nodal metastases have generally better outcome after surgical treatment.

Co-Author: Dr. Nikos Grivas (GR)

With the advent of novel imaging modalities, even metastases of 2mm can be detected using either 68Ga-PSMA-PET or USPIO (nano-)MRI4. Sensitivity of 68Ga-PSMA-PET scanning was found around 60% whereas specificity is generally reported over 95%5.

In a systematic review solely on studies using 68Ga-PSMA-11 PET tracing (Figure 1), positive scans were more frequently encountered in studies including men with recurrent disease compared to those with primary disease6 Jilg et al. found remarkably high sensitivity of 94% when the results were assessed on the main nodal regions7 but this dropped to 81% in the sub-regions indicating that removal of only PET-positive nodes would result in under-sampling.

Mean size of positive nodes was as high as 8.5mm whereas false negative nodal metastases still had a mean size of 3.8mm7. From studies on lymph node dissection in early nodal metastasized prostate cancer it became apparent that one in five metastases found on routine immunohistochemistry are smaller than 2mm12. There is no sign whatsoever that the 2mm cutoff is associated with a clinically relevant nodal metastases. Therefore, at the moment by definition 68Ga-PSMA-PET scanning will, always underestimate nodal metastases presence.

Nodal template Non-tumor specific tracers depicting nodal drainage patterns such as those applied in the sentinel node biopsy method have the potential to tailor nodal surgery, in particular, in those men with increased risk of nodal metastases where novel imaging methods such as USPIO-enhanced mpMRI and 68Ga-PSMA- PET fail to reveal macroscopic metastases and the proper template remains illusive.

These lymph node tracers currently consist of both radionuclides such as 99Tc and fluorophores such as indocyanine green (ICG). The former allowing for lymph drainage imaging preoperatively using scintigraphy, whereas ICG provides intraoperative near infra-red (NIR) imaging29 (Figure 2). In a systematic review the diagnostic accuracy of sentinel node techniques far exceeded that of any preoperative imaging technique for the detection of nodal metastases with the extended lymph node dissection as reference standard13.

Figure 2: ICG provides intraoperative near infra-red (NIR) imaging of lymph nodes

We therefore studied the role of a lymph drainage tracer to direct extended lymph node dissection and we observed both an improved nodal metastases yield as well as decreased biochemical recurrence rates in comparison to a historic control population14.

Prognosis prediction Older studies showed a non-linear correlation between androgen receptor expression in nodal metastases and overall survival15. For immunohistochemical detection of lymph node metastases from prostate cancer Queisser et al.16 suggested to use PSA, PSMA and androgen receptor expression. In light of PSMA tracing it is interesting to note that the percent of PSMA-positive cells was similar for primary tumor and nodal metastases, but the levels of expression per cell were lower in nodal metastases17.

Bostrom et al.18 reported that although PTEN loss was an independent predictor of outcome in men with node positive disease, TMPRSS2:ERG fusion status was not. Cell proliferation had an additional prognostic value to the number of positive nodes19.

Interestingly, neuroendocrine differentiation as assessed by chromogranin A expression was found more frequently in nodal metastases (2.6% of cells) compared to the primary tumor (1%), in particular in Gleason pattern 5 tumors (7.8% vs 1.4% of cells)20.

Clearly, management of nodal metastases in prostate cancer is still in its infancy. Routine radiation of nodal basins in localized prostate cancer was not associated with improved survival21 but selective radiation of areas most likely to contain or even have proven nodal disease was shown to be associated with a better than expected recurrence-free outcome2,14.

Moreover, the true role of nodal dissection is still debated22. A nomogram to predict outcome showed that presence of Gleason sum score > 7 was the strongest risk factor predicting cancer-specific survival in men with nodal metastases. These men were 5x more likely to die of disease11. In the same series, with each positive node removed cancer-specific mortality increased by 10%.

Locally treating nodal metastases In prostate cancer an increase in the burden of nodal disease is associated with poorer outcome. Local treatment of nodal metastases with surgery or radiotherapy may improve outcome, but clinical and in particular molecular predictors are only poorly understood. Template-guided surgery based on novel pre- and intraoperative imaging may improve nodal dissection.

References

Figure 1: A scan using 68G-PSMA PET tracing

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EUT Congress News

1. Touijer KA, Karnes RJ, Passoni N, Sjoberg DD, Assel M, Fossati N, et al. Survival Outcomes of Men with Lymph Node-positive Prostate Cancer After Radical Prostatectomy: A Comparative Analysis of Different Postoperative Management Strategies. European urology. 2017.

2. James ND, Spears MR, Clarke NW, Dearnaley DP, Mason MD, Parker CC, et al. Failure-Free Survival and Radiotherapy in Patients With Newly Diagnosed Nonmetastatic Prostate Cancer: Data From Patients in the Control Arm of the STAMPEDE Trial. JAMA Oncol.

2016;2(3):348-57.

3. Mottet N, Bellmunt J, Bolla M, Briers E, Cumberbatch MG, De Santis M, et al. EAU-ESTRO-SIOG Guidelines on Prostate Cancer. Part 1: Screening, Diagnosis, and Local Treatment with Curative Intent. European urology.

2017;71:618-29.

4. Thoeny HC, Barbieri S, Froehlich JM, Turkbey B, Choyke PL. Functional and Targeted Lymph Node Imaging in Prostate Cancer: Current Status and Future Challenges.

Radiology. 2017;285(3):728-43.

5. Udovicich C, Perera M, Hofman MS, Siva S, Del Rio A, Murphy DG, et al. (68)Ga-prostate-specific membrane antigen-positron emission tomography/computed tomography in advanced prostate cancer: Current state and future trends. Prostate Int. 2017;5(4):125-9.

6. Perera M, Papa N, Christidis D, Wetherell D, Hofman MS, Murphy DG, et al. Sensitivity, Specificity, and Predictors of Positive 68Ga-Prostate-specific Membrane Antigen Positron Emission Tomography in Advanced Prostate Cancer: A Systematic Review and Meta-analysis.

European urology. 2016.

7. Jilg CA, Drendel V, Rischke HC, Beck T, Vach W, Schaal K, et al. Diagnostic Accuracy of Ga-68-HBED-CC-PSMALigand-PET/CT before Salvage Lymph Node Dissection for Recurrent Prostate Cancer. Theranostics. 2017;7(6): 1770-80.

8. van Leeuwen PJ, Stricker P, Hruby G, Kneebone A, Ting F, Thompson B, et al. (68) Ga-PSMA has a high detection rate of prostate cancer recurrence outside the prostatic fossa in patients being considered for salvage radiation treatment. BJU international. 2016;117(5):732-9.

9. Schmidt-Hegemann NS, Fendler WP, Buchner A, Stief C, Rogowski P, Niyazi M, et al. Detection level and pattern of positive lesions using PSMA PET/CT for staging prior to radiation therapy. Radiat Oncol. 2017;12(1):176.

10. Calais J, Czernin J, Cao M, Kishan AU, Hegde JV, Shaverdian N, et al. (68)Ga-PSMA PET/CT mapping of prostate cancer biochemical recurrence following radical prostatectomy in 270 patients with PSA<1.0ng/ml: Impact on Salvage Radiotherapy Planning. Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 2017.

11. Abdollah F, Karnes RJ, Suardi N, Cozzarini C, Gandaglia G, Fossati N, et al. Predicting survival of patients with node-positive prostate cancer following multimodal treatment. European urology. 2014;65(3):554-62.

12. Rauscher I, Duwel C, Wirtz M, Schottelius M, Wester HJ, Schwamborn K, et al. Value of (111) In-prostate-specific membrane antigen (PSMA)-radioguided surgery for salvage lymphadenectomy in recurrent prostate cancer: correlation with histopathology and clinical follow-up.

BJU international. 2017;120(1):40-7.

13. Wit EM, Acar C, Grivas N, Yuan C, Horenblas S, Liedberg F, et al. Sentinel Node Procedure in Prostate Cancer: A Systematic Review to Assess Diagnostic Accuracy.

European urology. 2017;71(4):596-605.

14. Grivas N, Wit E, Pos F, de Jong J, Vegt E, Bex A, et al.

Sentinel Lymph Node Dissection to Select Clinically Node-negative Prostate Cancer Patients for Pelvic Radiation Therapy: Effect on Biochemical Recurrence and Systemic Progression. International journal of radiation oncology, biology, physics. 2017;97(2):347-54.

15. Sweat SD, Pacelli A, Bergstralh EJ, Slezak JM, Cheng L, Bostwick DG. Androgen receptor expression in prostate cancer lymph node metastases is predictive of outcome after surgery. The Journal of urology. 1999;161(4):1233-7.

16. Queisser A, Hagedorn SA, Braun M, Vogel W, Duensing S, Perner S. Comparison of different prostatic markers in lymph node and distant metastases of prostate cancer.

Mod Pathol. 2015;28(1):138-45.

17. Sweat SD, Pacelli A, Murphy GP, Bostwick DG. Prostatespecific membrane antigen expression is greatest in prostate adenocarcinoma and lymph node metastases.

Urology. 1998;52(4):637-40.

18. Bostrom PJ, Bjartell AS, Catto JW, Eggener SE, Lilja H, Loeb S, et al. Genomic Predictors of Outcome in Prostate Cancer. European urology. 2015;68(6):1033-44.

19. Cheng L, Pisansky TM, Sebo TJ, Leibovich BC, Ramnani DM, Weaver AL, et al. Cell proliferation in prostate cancer patients with lymph node metastasis: a marker for progression. Clin Cancer Res. 1999;5(10):2820-3.

20. Genitsch V, Zlobec I, Seiler R, Thalmann GN, Fleischmann A. Neuroendocrine Differentiation in Metastatic Conventional Prostate Cancer Is Significantly Increased in Lymph Node Metastases Compared to the Primary Tumors. Int J Mol Sci. 2017;18(8).

21. Muller AC, Eckert F, Paulsen F, Zips D, Stenzl A, Schilling D, et al. Nodal Clearance Rate and Long-Term Efficacy of Individualized Sentinel Node-Based Pelvic Intensity Modulated Radiation Therapy for High-Risk Prostate Cancer. International journal of radiation oncology, biology, physics. 2016;94(2):263-71.

22. Colicchia M, Sharma V, Abdollah F, Briganti A, Jeffrey Karnes R. Therapeutic Value of Standard Versus Extended Pelvic Lymph Node Dissection During Radical Prostatectomy for High-Risk Prostate Cancer. Curr Urol Rep. 2017;18(7):51.

Friday 16 March 12.30-15.45: Joint Session of the European Association of Urology (EAU) and the Korean Urological Association (KUA)

Saturday, 17 March 2018

Precision medicine in bladder cancer How can we precisely select the best systemic treatment?

Asst. Prof. Günter Niegisch Department of Urology Medical Faculty Heinrich-HeineUniversity Düsseldorf (DE)

Following a recent suggestion by the American Society of Clinical Oncology (ASCO), precision medicine in oncology aims to improve efficacy, to minimize side effects and to overcome acquired resistance of anti-cancer therapies by delivering ”the right cancer treatment to the right patient at the right dose and the right time”1.

To achieve these aims, appropriate prognostic and predictive biomarkers are required. Prognostic biomarkers may stratify patients according to their individual risk in order to decide whether systemic therapy is justified balancing potential toxicities against potential benefits (“who to treat”).

Predictive biomarkers may predict treatment responses to be expected by individual treatment approaches (“how to treat”).

Clinical use of appropriate biomarkers not only requires their identification by modern “pan-omics” methods (whole-genome sequencing, transcriptome analysis, proteomic and metabolomics approaches) but also their bioinformatic and functional integration in the pathophysiologic framework of the according neoplastic disease.

Precision oncology approaches have already been adopted or are getting more and more adopted regarding the treatment of a variety of malignancies (e.g. chronic myelogenous leukaemia, breast cancer, advanced non–small cell lung cancer). Recent high-throughput analyses may provide the scientific basis for a potential future implementation of precision oncology in the treatment of bladder cancer as well2-4.

Currently, unselected platin-based combination therapies are the mainstay both in the curative perioperative systemic treatment of muscle-invasive non-metastatic bladder cancer as well as in palliative treatment of non-resectable or metastatic bladder cancer. However, neoadjuvant (NAC) or adjuvant (AC) perioperative chemotherapy, using cisplatin-based regimes, improves oncological outcome only marginally (<10% improvement in five-year overall survival)5,6.

In the palliative setting, initial responses are observed only in up to 70% of patients and long term-survival is below 20%7. These observations in perioperative and palliative systemic treatment imply that in many UC patients a subpopulation of cancer cells evades cytostasis or cell death by inherent or acquired resistance to systemic treatments. This is apparently also true for recently introduced immune-oncological approaches as only about 25% of patients respond8-10.

Precision oncology Recent high-throughput analyses may provide the scientific basis for a potential future implementation of precision oncology in the treatment of bladder cancer as well and may improve treatment outcomes2-4. However, validation of these data in a prospective clinical setting is still missing as is integration of a substantial part of these data in the mainframe of pathophysiology of bladder cancer.

Further, available data from these analyses as well as of other projects is largely restricted to primary cancer tissue. Biology of these primary tissues may differ significantly from metastatic tissue, especially following an antineoplastic therapy11. Accordingly, response prediction in primary tissues may not be related to actual response of metastases.

Future precision oncology approaches are likely to focus first on perioperative therapy before according options in the metastatic setting may become tangible.

In this context, prognostic biomarkers may help to identify patients unlikely to benefit from perioperative systemic therapy, as well as patients most likely to benefit. Examples for prognostic Saturday, 17 March 2018

biomarkers are a recently proposed 20-gene model predicting the likelihood of lymphnodal disease as well as a recently proposed risk model developed by an integrated analysis of the TCGA data2,12.

In addition, predictive biomarkers will help to delineate the optimal therapy to each individual patient. In retrospective analyses of patients undergoing platinum-based neoadjuvant chemotherapy, the potential value of predictive biomarkers has already been demonstrated. As example, response to neoadjuvant chemotherapy has been demonstrated to be dependent on molecular subtypes of bladder cancer4,13.

However, these data lack prospective evaluation.

Further, even with an appropriate predictive subtype, a significant number of patients will not benefit from neoadjuvant chemotherapy nevertheless. Lastly, it remains unclear if any systemic treatment should be offered to patients who are assumed to be non-responders based on their molecular subtype.

With regard to the latter point, integration of high-throughput data may predict individual treatment approaches beyond conventional systemic therapy as well. Only recently, the TCGA consortium proposed a potential diagnostic and therapeutic treatment workflow based on their multi-platform analyses identifying key drivers within the specific molecular subtypes (Figure 1).

Next to conventional chemotherapy, novel antineoplastic treatment (immune-oncological approaches, FGFR3 inhibitors, other targeted agents) have been included in this proposal as well. However, both preclinical as well as clinical validation is needed before translation into clinical practice is possible.

“Future precision oncology approaches are likely to focus first on perioperative therapy before according options in the metastatic setting may become tangible.”

Intra-tumor heterogeneity While advances in precision oncology in the perioperative systemic treatment of bladder cancer clinical may be expected in the medium term, implementation in the metastatic, especially in the post-platinum, setting may be limited not only by inter- but also by intra-tumor heterogeneity.

In this context, a recent comparative analysis of primary and metastatic tumor tissue before and after platin-based chemotherapy demonstrated the evolution of distinct molecular features during growth and metastasis as well as before and after systemic therapy11.

Figure 1: Diagnostic and therapeutic algorithm as proposed by the TCGA consortium as a framework for prospective hypothesis testing in clinical trials2

in urothelial urinary bladder cancer. Cancer Control, 2013.

20(3): p. 200-10.

8. Bellmunt, J., et al., Pembrolizumab as Second-Line Therapy for Advanced Urothelial Carcinoma. N Engl J Med, 2017. 376(11): p. 1015-1026.

9. Sharma, P., et al., Nivolumab in metastatic urothelial carcinoma after platinum therapy (CheckMate 275): a multicentre, single-arm, phase 2 trial. Lancet Oncol, 2017.

18(3): p. 312-322.

10. Rosenberg, J.E., et al., Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy: a single-arm, multicentre, phase 2 trial. Lancet, 2016. 387(10031): p. 1909-20.

11. Faltas, B.M., et al., Clonal evolution of chemotherapyresistant urothelial carcinoma. Nat Genet, 2016. 48(12): p.

1490-1499.

12. Smith, S.C., et al., A 20-gene model for molecular nodal staging of bladder cancer: development and prospective assessment. Lancet Oncol, 2011. 12(2): p. 137-43.

“...it remains unclear if any systemic treatment should be offered to patients who are assumed to be non-responders based on their molecular subtype.”

13. Choi, W., et al., Identification of distinct basal and luminal subtypes of muscle-invasive bladder cancer with different sensitivities to frontline chemotherapy. Cancer Cell, 2014. 25(2): p. 152-65.

Saturday 17 March 10.15-14.00: Joint meeting of the EAU Section of Urological Imaging (ESUI), the EAU Section of Uropathology (ESUP) and the EAU Section of Urological Research (ESUR) How tumour heterogeneity influences our practice today and tomorrow

UROLOGY CLEARLY DEFINED

In summary, important initial steps towards precision oncology in bladder cancer therapy have been taken. Nevertheless, validation of these data as well as integration of these data in the pathophysiologic mainframe of bladder cancer in order to allow tailoring individual diagnostic and therapeutic approaches are essential.

References 1. Schwartzberg, L., et al., Precision Oncology: Who, How, What, When, and When Not? Am Soc Clin Oncol Educ Book, 2017. 37: p. 160-169.

2. Robertson, A.G., et al., Comprehensive Molecular Characterization of Muscle-Invasive Bladder Cancer.

Cell, 2017. 171(3): p. 540-556 e25.

3. Sjodahl, G., et al., Molecular classification of urothelial carcinoma: global mRNA classification versus tumourcell phenotype classification. J Pathol, 2017. 242(1): p. 113-125.

4. Seiler, R., et al., Impact of Molecular Subtypes in Muscle-invasive Bladder Cancer on Predicting Response and Survival after Neoadjuvant Chemotherapy. Eur Urol, 2017. 72(4): p. 544-554.

5. Advanced Bladder Cancer Overview, C., Neoadjuvant chemotherapy for invasive bladder cancer. Cochrane Database Syst Rev, 2005(2): p. CD005246.

6. Leow, J.J., et al., A systematic review and meta-analysis of adjuvant and neoadjuvant chemotherapy for upper tract urothelial carcinoma. Eur Urol, 2014. 66(3): p.

529-41.

7. Gupta, S. and A. Mahipal, Role of systemic chemotherapy

Cheers!

Have an after-work beer with us at our booth D58 and discover our Clearly Defined Urology Solutions.

First come, first served.

On Saturday and Sunday as of 17.00!

Hitachi Medical Systems Europe Holding AG www.hitachi-medical-systems.eu

EUT Congress News

9

Today’s European Urology Events How to write the introduction and methods

ESU Writing Course Part 1

March 17th 8.30 – 10.30 Orange Area, Room 1 (Level 0)

Aims and objectives: Understand how to construct a well written introduction and methods section for your manuscript. Learn how to work through examples of good and bad practices, and understand key points when writing. Obtain insight from editors on what they expect to see.

• To understand what makes a good introduction • To understand what makes a good methods section • To understand about systematic reviews and meta-analysis • To learn from experienced editors

How to write results and discussion

ESU Writing Course Part 2

March 17th

Aims and objectives: Learn the best way to draft the results and discussion section of a scientific paper.

Understand how to work through examples of good and bad practices, to find the key points of the manuscript. Obtain insight from editors on what they expect to see.

• To understand what makes a good results section and how to best present your data • To understand what makes a good discussion • To learn from experienced editors

1. Welcome Jim Catto, Sheffield (GB) 2. How to write an introduction Giacomo Novara, Padova (IT) 3. Group working I 4. How to write the methods section Christian Gratzke, Munich (DE) 5. Key features for a systematic review Marcus Cumberbatch, Sheffield (GB) 6. What to look for in the statistics section Christian Gratzke, Munich (DE) 7. Group working II 8. Questions and answers

1. Welcome Jim Catto, Sheffield (GB) 2. How to write the results chapter Stephen Boorjian, Rochester (US) 3. Choosing and presenting your statistical analyses Melissa Assel, New York (US) 4. Group working I 5. Writing the discussion section Jean-Nicolas Cornu, Rouen (FR) 6. What the editor looks at when reviewing the results and discussion Stephen Boorjian, Rochester (US) 7. Group working II 8. Questions and answers

12:00 – 14:00 Orange Area, Room 1 (Level 0)

Platinum hour

March 17th - 18th 16.00 – 18.00 European Urology booth #C3-C29

We would like to invite you to attend the Platinum Hour drinks reception to meet and greet the editors, authors and reviewers of the European Urology family of three: European Urology, European Urology Focus and European Urology Oncology. Please join us to toast to the family’s new sister journal European Urology Oncology.

This new journal complements the family by delivering high quality research while pursuing the goal of a multi-disciplinary approach. Urology, Medical Oncology, Radiation Therapy, Imaging, Pathology and Basic Research working together with the same final aim: to improve patient care. If you’ve got practice changing, groundbreaking research in urological oncology, you can directly submit your original article via this link: ees.elsevier.com/euonco.

We look forward to answer any questions about the new journal, or another member of the European Urology family, during the drinks reception at our booth!

europeanurology.com eufocus.europeanurology.com europeanurology.com/euoncology

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EUT Congress News

Saturday, 17 March 2018

Infectious complications and fURS fURS procedure may lead to severe infective complications if crucial measures are not properly taken Prof. Kemal Sarica Chairman EAU Section of Urolithiasis ( EULIS) Chief, Dept.of Urology Medical School Kafkas University Kars (TR)

Surgical management of renal stones has substantially changed in the last two decades where endourological procedures, such as percutaneous nephrolithotomy (PCNL) and flexible uretero(reno)scopy (fURS) became the standard treatment options for the minimal invasive removal of renal stones.

Related with this issue, increasing experience gained in the ureteroscopic management of upper urinary tract calculi as well as the marked improvements in the instrument technology have increased the popularity of fURS as a safe and acceptable treatment alternative for small-tomoderate-sized renal stones up to 20 mm1.

Published data on this aspect so far has clearly demonstrated that fURS in experienced hands may reveal potentially higher stone-free rates (SFR) than extracorporeal shock wave lithotripsy (ESWL) and lower morbidity than PCNL in the treatment of such stones. Morover, flexible uretero(reno)scopic laser disintegration and successful removal of these stones with high SFR did reduce the morbidity and hospital stay to a certain extent in the majority of the cases.

However, despite its minimal invasive and efficient natüre, fURS procedure is not completely complication-free and some certain problems could be encountered either during and/or early post-operative follow-up period. Such problems could be partly explained with the rapid expansion of URS indications to larger and more complicated stones and to elderly patients with significant comorbidities originating from such a high success rate and low complication rates obtained.

Relevant studies indicated well that inappropriate widening of the indications might result in a higher incidence of severe complications, including febrile urinary tract infection (UTI), need for blood transfusion, renal dysfunction or septic shock.

Related with this issue, by using the Clinical Research Office of the Endourological Society (CROES) database in their original study, De la Rostte et al., analyzed 11,885 patients treated with URS (consisted of data from 114 centers in 32 countries) and reported the stone-free as well as post-operative complications rates to be 85.6 % and 3.5 % respectively2.

The most frequent complication noted was fever (2.8 %) in that study. Of the complications noted so far after fURS, while infection affecting up to 1.8 % of patients undergoing flexible uretero(reno)scopy and laser lithotripsy has been reported1.More recently, Fan showed in a retrospective study that the incidence of infectious complications after fURS may range between 1.7 and 18.8 %3.

Several subsequent studies have also reported that urosepsis can be a majör problem for management despite the use of appropriate antibiotics prior to the endourological procedures4-6.

As previously mentioned, infective complications following fURS remain a decisive issue and it has been reported that this procedure may still have unforeseen post-operative systemic and sometimes life-threatening infection despite a well-performed appropriate pre-operative antibiotic therapy along with the use of ureteral access sheath (UAS) which effectively reduces the likelihood of pyelolymphatic or pyelovenous backflow7. Access sheaths also allow for continuous irrigation of the renal pelvis and improved stone clearance, as well as lower renal pelvic pressures that may be protective against pyelovenous and pyelolymphatic backflow8,9.

Regarding the risk of infective complications after a successful fURS, while it is highly crucial to postpone the treatment of stones in the presence of an urinary tract infection, a well-confirmed negative preSaturday, 17 March 2018

operative urine culture prior to procedure however has not been found to guarantee the absence of post-operative infection. fURS procedure could be associated with higher risk of post-operative infection in cases with infected stones, longer operative times, and the presence of residual fragments as well as foreign bodies (10).On the other hand, again higher intrapelvic pressure levels during fURS procedure could be associated with post-operative sepsis and Zhong et al demonstrated that the patients who had sustained an intrapelvic pressure ≥30 mmHg were more likely to develop post-operative fever11.

However, although the UAS reduces the renal pelvic pressure and may help to reduce the intra-operative absorption of lavage fluid, the authors did not find any increased risk of infective complications when it was not used (p = 0.43). In the same direction, several reports have not found any association between intrapelvic pressures and the incidence of post-operative fever after PCNL12.

Regarding the other possible risk factors for infectious problems after fURS, in their original study Martov et al.13 have reported that the patients with such infective complications had significant comorbidities (coronary heart disease, CKD, alteration of lipid metabolism, anticoagulant therapy) at univariate analysis. An increased risk of infectious complications following FURS was found to be associated with some comorbidities like Crohn’s, cardiovascular disease, high ASA score and high stone burden.

Thus, the increased risk of infectious complications among cases with greater comorbidities emphasizes the importance of judicious patient selection for this type of procedure. Additionally, Fan et al. found that pyuria, operative duration, and infectious stones were independently related to infectious complications14.

On the other hand, and equally important, intraoperative stone culture has been found to be more reliable than a pre-operative urine culture in guiding both the antibiotic therapy in patients who develop sepsis and also identifying patients at risk for post-operative sepsis. These results have clearly outlined the importance of obtaining an intraoperative stone culture in a routinely performed manner.

Studies have shown that 8% of the patients with positive stone cultures developed sepsis and this value was significantly greater than the percentage with negative stone cultures who developed sepsis (1 %). As a result, data from the stone culture were found to be critical in determining the proper treatment in these patients and more importantly, the stone culture seemed to have a higher association with post-operative sepsis than did the pre-operative urine culture (15,16).

“...despite its minimal invasive nature and successful outcomes, fURS procedure may results in severe infective complications if necessary measures are not taken well...”

Last but not least, sepsis after URS is a major complication which should inevitably be avoided.

However, only a few studies clearly described the incidence of sepsis after URS or endourological procedures. Geavlete reported that the incidence of fever and sepsis was 1.13 % among 2,735 cases treated with semi-rigid URS at a single center8.

Eswara et al. reported that the incidence of sepsis was 3.0 % (11/328) after endourological procedures, including 54 cases of percutaneous nephrolithotomy17.

Finally,Youssef et al. reported sepsis developed post-operatively in two patients (1.4 %) with diabetes (one with and one without previous sepsis), and post-operative fever developed in five patients with previous sepsis. Regarding the possible risk factors, while Sohn and colleagues reported that bacteriuria and catheterization were the strongest risk factors for severe febrile complications18, Youssef et al. demonstrated that URS with pre-operative sepsis had

Surgeons should be aware of potential serious infectious complications arising from fURS procedures and the corresponding management strategies.

higher complication rates, including post-operative high fever and sepsis, than URS without preoperative sepsis19.

Infective complications In the light of the facts mentioned above and despite its minimal invasive nature and successful outcomes, fURS procedure may results in severe infective complications if necessary measures are not taken well among which the proper selection of the cases is of utmost importance.

“...intraoperative stone culture has been found to be more reliable than a pre-operative urine culture in guiding both the antibiotic therapy in patients who develop sepsis...”

Surgeons have to be aware of the possibility of serious infectious complications and their management strategies. It is obvious that urine culture findings should be obtained in all patients before the procedure and an infection-free urine noted after an appropriate antibiotic management will certainly limit the risk of infectious complications to a considerable extent after fURS. Additionally, published data do indicate that the proper and careful use of an appropraitely sized ureteral access sheath during the procedure may allow a successful and, more importantly, infectionfree procedure.

In summary, culture antibiogram-based appropriate antibiotic administration, lower irrigation pressure during the procedure along with an unobstructed peri-operative urinary drainage, obtaining intra-operative urine or stone culture are the established important factors in effectively preventing post-operative infectious complications, including sepsis.

References 1. Knopf HJ, Graff HJ, Schulze H (2003) Perioperative antibiotic prophylaxis in ureteroscopic stone removal.

Eur Urol 44:115 2. de la Rosette J, Denstedt J, Geavlete P et al (2014) The clini- cal research office of the endourological society ureteroscopy global study: indications, complications, and outcomes in 11,885 patients. J Endourol 28:131–139.

3. Fan S, Gong B, Zet Hao et al (2015) Risk factors of infectious complications following flexible ureteroscope with a holmium laser: a retrospective study. Int J Clin Exp Med 8(7):11252 .

4. Lee WJ, Smith AD, Cubelli V et al (1987) Complications of percutaneous nephrolithotomy. AJR Am J Roentgenol 148:177.

5. Michel MS, Trojan L, Rassweiler JJ (2007) Complications in percutaneous nephrolithotomy. Eur Urol 51:899.

6. Rao PN, Dube DA, Weightman NC et al (1991) Prediction of septicemia following endourological manipulation for stones in the upper urinary tract. J Urol 146:955.

7. O’Keeffe NK, Mortimer AJ, Sambrook PA, Rao PN (1993) Severe sepsis following percutaneous or endoscopic procedures for urinary tract stones. Br J Urol 72:277–283 8. Geavlete P, Georgescu D, Niţa ̆ G, Mirciulescu V, Cauni V (2006) Complications of 2735 retrograde semirigid ureteroscopy procedures: a single-center experience. J Endourol 20:179–185 9. Troxel SA, Low RK (2002) Renal intrapelvic pressure during percutaneous nephrolithotomy and its correlation with the development of postoperative fever. J Urol 168:1348–1351 10. Sohn DW, Kim SW, Hong CG, Yoon BI, Ha US, Cho YH (2013) Risk factors of infectious complication after uretero- scopic procedures of the upper urinary tract. J Infect Chemother 19:1102–1108 11. Zhong W, Zeng G, Wu K, Li X, Chen W, Yang H (2008) Does a smaller tract in percutaneous nephrolithotomy contribute to high renal pelvic pressure and postoperative fever. J Urol 22:2147–2151 12. Troxel SA, Low RK (2002) Renal intrapelvic pressure during percutaneous nephrolithotomy and its correlation with the development of postoperative fever. J Urol 168:1348–1351 13. Alexey Martov, Stavros Gravas, Masoud Etemadian et al (2015) Postoperative infection rates in patients with a negative baseline urine culture undergoing ureteroscopic stone removal: a matched case-control analysis on antibiotic prophylaxis from the CROES URS global study. J Endourol 29:171–180 14. Fan S, Gong B, Zet Hao et al (2015) Risk factors of infectious complications following flexible ureteroscope with a holmium laser: a retrospective study. Int J Clin Exp Med 8(7):11252 15. Wollin DA, Joyce AD, Gupta M, Wong MYC, Laguna P, Gravas S, Gutierrez J, Cormio L, Wang K, Preminger GM1. : Antibiotic use and the prevention and management of infectious complications in stone disease. World J Urol. 2017 Sep;35(9):1369-1379.

16. Motamedinia P, Korets R, Badalato G, Gupta M.: Perioperative cultures and the role of antibiotics during stone surgery. Transl Androl Urol. 2014 Sep;3(3):297301.

17. Eswara JR, Shariftabrizi A, Sacco D (2013) Positive stone culture is associated with a higher rate of sepsis after endourologi- cal procedures. Urolithiasis 41:411–414 18. Sohn DW, Kim SW, Hong CG, Yoon BI, Ha US, Cho YH (2013) Risk factors of infectious complication after uretero- scopic procedures of the upper urinary tract. J Infect Chemother 19:1102–1108 19. Youssef RF, Neisius A, Goldsmith ZG et al (2014) Clinical out- comes after ureteroscopic lithotripsy in patients who initially presented with urosepsis: matched pair comparison with elective ureteroscopy. J Endourol 28:1439–1443

Saturday 17 March 10.15-14.30: Meeting of the EAU Section of Urolithiasis (EULIS), Management of stones: Advancing technology, increasing experience and changing concepts. Where are we in 2018?

EUT Congress News

11

Ernest Desnos: Honouring urology historians Historical Exhibition features artefacts from Desnos’ career and much more

By Loek Keizer

from the early 20th century on which the EAU Ernest Desnos Prize is based.

Last night saw the presentation of the first EAU Ernest Desnos Prize for contributions to the field of the history of urology. The EAU History Office unanimously voted to honour Prof. Sergio Musitelli (IT), long-term expert of the Office and (co)-author of several unique volumes dedicated to the earliest history of urological procedures.

In honour of our host country this year, the exhibition also features several highlights from the history of urology in Denmark and the Scandinavian countries. It is completed with items related to the First World War, the end of which was one century ago this year.

The First World War disrupted the development of urology, and particularly the international cooperation within the field just as it was reaching maturity.

Several prominent British urologists were veterans of the Great War, and the exhibition explores their time of service and subsequent accomplishments in urology.

Musitelli, who turned 90 this year, was Visiting Professor of the History of Urology, Sexology and Andrology at the University of Pavia for many years, following a long career in philosophy, ancient arts, oriental literature and languages and the history of ancient science and medicine.

Since the start of the EAU History Office, Mustelli functions as a professional history expert and participates in all activities. Based on his position as an expert in history, he was one of the most active contributors to the work of the EAU History Office, not only with numerous articles and books but also in reviewing submitted articles for the annual De Historia Urologiae Europaeae volumes. Furthermore, he was responsible for a detailed and reliable index of all published volumes of these series.

Prof. Sergio Musitelli, recipient of the first EAU Ernest Desnos Prize

accomplishments are co-founding the AFU and later the SIU, as well as treating Emperor Napoleon III for a bladder stone in 1873 and major pioneering work on prostate brachytherapy.

However his most significant contribution was in the field of the History of Urology. Therefore his ‘magnum In the words of EAU History Office Chairman Prof. opus’ is the first book on the History of Urology ever.

Philip Van Kerrebroeck (BE): “Sergio’s own This book was published in 1914 as “Histoire de publications bring in an original viewpoint, always l’Urologie” (History of Urology, Paris. Doin éditeur, based on extensive literature search, but with a very 1914). The large volume presents, in 294 pages with critical interpretation of the available material. He 196 beautiful black and white illustrations and nine teaches us all that history, and hence also history of urology is much more than telling an interesting story, coloured reproductions, a complete overview on the but that it is also a science. Hence he was responsible History of Urological Surgery and Urology from its origins to the beginning of the 20th century. for a further professionalization of historiography in the field of urology, and we all profit from his efforts.”

Historical Exhibition This year’s Historical Exhibition, which is to open at The prize bears the name of Dr. Ernest Desnos the EAU Booth in the Exhibition Hall this morning (1852-1925), as a tribute to this pioneering French features several items from Desnos’ impressive urologist who was also an eminent urology historian oeuvre. His most notable historical works, some and who wrote the first book devoted solely to the personal artefacts, and the original Desnos medal history of urology. Not least of Desnos’

New publications A good opportunity to visit the Historical Exhibition would be when you collect your copies of the latest EAU publications. EAU members can collect their copy of the 25th Anniversary Edition of De Historia Urologiae Europaeae, the congress gift For this Relief, Much Thanks! by Dr. Johan Mattelaer, as well as other membership benefits, depending on your entitlements.

Mattelaer’s latest publication explores the depiction of urination in art, both classical and contemporary. It is a beautifully illustrated coffee table book that celebrates our field and offers unique insights.

Delivered by The University of Edinburgh in partnership with The Royal College of Surgeons of Edinburgh

Desnos’ Histoire de l’Urologie (1914), considered to be the first single volume publication on the history of urology

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The 25th Anniversary Edition of De Historia features contributions from past editors, special attention for the inaugural Ernest Desnos Prize winner, as well as the usual wide-ranging articles that cover the history of urology.

The Historical Exhibition is located across the EAU Booth (H69). Publications can be collected at the EAU Booth. The EAU Booth is open on the following days:

Master of Surgery in Urology The Degree Programme

The original Desnos medal from the early 20th century on which the EAU Ernest Desnos Prize medal is based

Paediatric Urology Transplant Nephrology Stone Disease Urethral reconstruction Male incontinence Andrology Female Urology Neurourology Bladder Cancer Renal Cancer Prostate Cancer Penile Cancer Testicular Cancer New technologies Minimal access developments

Saturday 17 March, 09:30-18:15 Sunday 18 March, 09:30-18:15 Monday 19 March, 09:30-15:30

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www.urochm.rcsed.ac.uk 12

EUT Congress News

Saturday, 17 March 2018

EAU Guidelines: Ensuring consistent European urological care Variations in practice exist despite high-quality standards Prof. Dr. James N’Dow Chairman, EAU Guidelines Office Dept. of Urology University of Aberdeen Aberdeen (GB)

Adherence to national and international guidelines is sub-optimal throughout Europe. In fact, significant gaps currently exists in terms of the application and use in clinical practice of the EAU Guidelines, even though they are based on standardised high-quality methodology and are endorsed by all 28 European Member States.

For example, we are aware that in some countries, approximately one out of four men with prostate cancer received androgen deprivation therapy despite the fact it is not recommended by the EAU Guidelines.

This in turn increases the risk of short- and long-term side effects in these patients, and the costs related to disease management.

In addition, studies have reported that despite clear EAU guideline recommendations advocating the use of intravesical chemotherapy post-surgical resection in non-muscle invasive bladder cancer, adherence to these guidelines is low and varies widely, with estimates ranging from 22% to 71% in a sample of five European Union countries.

Guideline developers need to ensure that guidelines have a clear structure and local applicability in order for guidelines to be useful in different settings and healthcare systems. Although guidelines have the potential to improve care by promoting effective interventions and discouraging ineffective ones, publication of guidance alone is unlikely to optimise practice. Development of guidelines must be supported by an effective dissemination and implementation strategy. The EAU have successfully developed an effective mass dissemination platform through Twitter. The EAU Twitter platform has also been used to estimate adherence to EAU guidelines recommendations. The EAU Guidelines Office ‘IMAGINE’ project (IMpact Assessment of Guidelines Implementation and Education) has been developed to effectively tackle the issues of non-adherence and Another limitation in relation to guidelines implementation with the ultimate goal of ensuring all development is that guideline panels are often limited patients across Europe receive the best evidenceto those with clinical and methodological expertise. based standardised care.

The voice of the other stakeholder groups in the design and delivery of healthcare (e.g. patients, Why should we improve clinical practice guidelines carers, charitable organisations and industry) is often adherence? missing from these discussions. Given the emphasis If evidence-based best practice recommendations are on patient-focused outcomes and the need for not disseminated effectively and knowledge is not guidelines to be responsive to stakeholder needs, actively transferred, variations in practice are likely to strong arguments exist for the inclusion of all of the occur. Where variations in practice occur, healthcare is key stakeholder groups in the guidelines development unequal within nation states and across European process. Achieving true stakeholder engagement in member states, whilst health systems are most likely the Guidelines development, delivery and inefficient. Furthermore, if all stakeholders, including implementation process will: patients, are not meaningfully included in consultations to prioritise research areas, to • Guarantee that all stakeholders have confidence determine which outcomes are the most important, in the guidelines development process and as and to ensure recommendations are phrased such the resulting recommendations; appropriately, then they are denied informed shared-decision making.

• Ensure that the recommendations are appropriate, achievable and can be translated There is an urgent need to harmonise clinical practice into corresponding health behaviour leading to throughout Europe and guidelines are the ideal better treatment compliance and better health framework for doing so. The key to this is to ensure outcomes; and the availability of high-quality European-wide guidelines, which are robustly established, fit for • Result in recommendations and guidelines which purpose and comprehensive. The EAU guidelines are facilitate person-centred care. an excellent demonstrator model for achieving

Cover of the new 2018 EAU Guidelines edition

harmonisation across all EU member states. It is fundamentally important that such guidelines have a high degree of visibility, uptake and adherence by clinicians and healthcare providers.

Whilst the EAU guidelines are now endorsed by all EU member states, European Union/European Commission endorsement would undoubtedly increase the recognition of the importance of guidelines in general, as well as their visibility, dissemination and implementation. If this integrated model for the development, dissemination and implementation of European-wide guidelines for urology could be achieved, the potential for other clinical areas to apply this cohesive model would be promising with the prospective overwhelmingly positive impact on harmonisation and a far more effective healthcare provision in Europe.

URO 84 2.0 02/2018/A-E

There are also similar concerns regarding non-adherence to non-oncological guidelines in urology. A study conducted to assess adherence levels to the Guidelines on Urinary Incontinence of the Dutch College of General Practitioners found that approximately only a third of surveyed clinicians complied with treatment recommendations.

Reasons for variation in practice and non-adherence to guidelines Guidelines are ideally informed by systematic reviews of the evidence and those systematic reviews are in turn informed by primary research of treatment effectiveness. A major hurdle for conducting systematic reviews occurs when outcomes are not defined, measured and reported in the same way and at the same time point across the included studies.

This heterogeneity means that synthesising and creating meaningful and impactful evidence summaries is often difficult in urology. For guideline panels, it is difficult to make strong recommendations for or against treatment interventions in the most transparent way because they must rely on suboptimal summaries of the evidence.

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Saturday, 17 March 2018

EUT Congress News

13

Update in vaginoplasty technique Prospective randomized studies needed to identify ‘ideal’ vaginopasty Prof. Ervin Kocjancic University of Illinois Dept. of Urology Chicago (USA)

Co-Author: Ömer Acar, Istanbul (TR) Gender dysphoria (GD) can be described as a discrepancy between the gender assigned at birth and gender identity (Bizic et al.). Patients with GD exhibit strong cross-gender identification, persistent discomfort with their anatomical sex and a sense of inappropriateness in the gender role of that sex which lead to distress and bother in social, occupational, and other important areas of functioning (Horbach et al.).

Regarding nontransgender vaginoplasty; the Frank method, which was described in 1938, involves the utility of graduated vaginal dilators to create a vagina or augment an existing structure inadequate for sexual intercourse (Davies et al., Ismail Pratt et al.). The “semisurgical” Vechietti procedure, which requires elasticity of the vaginal skin, allows creation of neovagina by passive traction rather than dilation.

Herein an acrylic “olive” with attached tension threads is placed at the vaginal dimple and the threads are passed under laparoscopic control from the vaginal dimple to a traction device on the abdominal wall (Davies et al.). The Davydov technique, which may also be performed laparoscopically and is more suitable for those patients with perineal scarring and/or vaginal inelasticity, includes liberation of peritoneum from the pelvic side walls and the Pouch of Douglas. Neovagina is created by suturing a vaginal “roof” of peritoneum and then filled with a soft mould which remains in place for one week (Davies et al., Ismail I et al.).

Intestinal vaginoplasty, which will be discussed in more detail as related to transgender vaginoplasty, can also be applied for non-transgender patients.

Recent studies have shown that the prevalence of trans females and trans males to be 1:12,900 and 1:33,800, respectively. Individuals with GD are becoming increasingly more accepted in society (Colebunders et al., De Cuypere et al.) and therefore the number of patients who feel confident enough to seek gender reassignment surgery has increased substantially (Dhejne et al.).

In transgender vaginoplasty, surgical techniques can be divided into three main categories according to the Figuur 2: Disasembeling of the penis and preparation of the neo clitoris nature and origin of the tissue(s) used for reconstruction: Skin grafts; Penile-scrotal skin flaps (Penile skin inversion technique); and pedicled small or large bowel segments (Intestinal vaginoplasty) bearing surface, sensate nature, thin connective tissue formation between the rectum and neovagina. The overall incidence of rectovaginal fistula was reported to and relatively minimal tendency to contract represent The main goals of vaginoplasty are to achieve an be 1% (Bouman et al.). In such an event, surgical the main advantages of using penile skin-based flaps esthetically and functionally ideal perineogenital (Bizic et al.). In cases where the penile skin is deficient correction can be done via double-layer of vascularized The treatment of patients with GD requires a complex that will satisfy the patient (Bizic et al., Karim (circumcision, micropenis etc.), several technical tissue +/- temporary colostomy. Being aware of this multidisciplinary approach which consists of et al.). The neovagina should be moist, elastic and possibility, prompt intraoperative recognition, refinements can be applied such as combining the psychiatric and psychologic evaluation, cross-sex hairless with a depth of at least 10 cm and a diameter penile skin flap with scrotal (Bizic et al., Selvaggi et al.) appropriate surgical correction, preoperative bowel hormonal therapy and reconstructive surgical preparation and perioperative antibiotic prophylaxis of 3-4 cm. The clitoris should be small, obscured and and/or urethral flaps (Bizic et al., Perovic et al.). procedures aiming to modify the body image and sensitive enough to enable complete arousal. Labia Utilizing a perineal flap together with a scrotal graft in will help to minimize the potential problems function toward the desired gender (Bizic et al.). The minora and majora should resemble the female vulva addition to penile skin may also serve well to lengthen associated with rectal injury.

World Professional Association of Transgender Health as much as possible. Innervation of the new genitalia the neovaginal cavity (Kocjancic et al.).

(WPATH) has established the standards of care for the complex should be functionally intact in order to offer Labiaplasty and clitoroplasty are integral parts of a multidisciplinary treatment of such individuals. Before a satisfactory level of erogenous stimulation during Van Noort et al. combined penile skin with a scrotal full vaginoplasty procedure. Usually the scrotal skin and the undergoing genital reconstruction; transgender base of the penile skin is used to create labia majora sexual intercourse (Bizic et al., Karim et al., Selvaggi et thickness skin graft and/or a posteriorly based scrotal patients are required to provide two recommendation al.). Transwomen who prefer an esthetic outcome and miora, respectively. Adipose tissue around the skin flap. The major drawback of this modification letters from two independent, certified pyschiatrists spermatic cord can additionally be used for labiaplasty. without a functional vagina can undergo a vulvoplasty would be the introduction of hair-bearing scrotal skin and a letter of confirmation documenting their within the posterior lining of the vagina if hair removal Spatulated distal urethra can be used to create the floor without vaginoplasty. compliance with the hormonal therapy arranged by of the vestibulum. Clitoris is constructed with the dorsal has not been done peroperatively. To avoid this, the endocrinologist for a period of at least one year permanent epilation can be accomplished before portion of the glans penis in a horseshoe or W-pattern 1. Skin grafts (wpath.org). vaginoplasty via laser therapy or electrolysis in patients (Colebunders et al., Perovic et al.). It is of utmost Local nongenital skin flaps, full-thickness skin grafts importance to preserve the dorsal neurovascular with a limited amount of penile skin. Alternatively, the (FTG) or split-thickness skin grafts (STG) have been The core surgical interventions that are applied pedicle to enable the neoclitoris react to sexual graft can be meticulosly cleared off adipose tissue and used for neovagina formation. Hage and Karim within the context of trans women are; facial stimulus. Additionally, the labia majora and minora hair follicles immediately after harvest at the harvested FTG from the lower abdomen and a used a feminizing surgery, voice surgery and backbench. Perovic and Djordevic has described should be sutured to the de-epithelialized area of the mold to insert it in the neovaginal cavity. They chondrolaryngoplasty, breast augmentation, and another technique in which a spatulated urethral flap neoclitoris so that the neoclitoris looks conical and mentioned no postoperative complications after a orchiectomy, penectomy and vaginoplasty. hidden. This type of clitoroplasty provides good was fixed onto the penile skin flap to increase follow-up duration of seven months. All of their Vaginoplasty, which is the last step of the transition neovaginal length and width. This addition also served sensitivity and sexual satisfaction for the patients (Bizic patients (n= 6) were reported to be “subjectively” process, depicts the construction of a vagina that et al., Selvaggi et al.). Although flaps contract much less well for the vaginal moisture and lubrication given the pleased with the cosmetic and functional outcome. resembles a biological vagina in form and function. well vascularized nature of the urethral flap. often than grafts, patients are still required to use a Mean neovaginal depth and width was 12 and 3 cm, This procedure includes orchiectomy (can be dilator postoperatively for at least one year to prevent respectively (Horbach et al., Hage et al.). performed as a first stage procedure before vaginal Buncamper et al. used additional full-thickness skin neovaginal and introital stenosis. reconstruction), amputation of the penis, creation Siemssen and Matzen used FTG of penile skin, STG or a graft in the penile inversion vaginoplasties of and lining of the neovaginal cavity, reconstruction of 3. Pedicled small or large bowel segments (intestinal combination of both in a group of 11 patients. They did transgender women who have a penile skin length of the urethral meatus and construction of the labia and not report on neovaginal dimensions, patient less than 12cm in an effort to obtain more vaginal vaginoplasty) clitoris. Vaginoplasty can also be applied to biological satisfaction and quality of life outcomes. Overall, depth and create an esthetically superior vulva. In their Intestinal vaginoplasty has become a valid option that women with disorders of sexual development (such case-control study (n= 100, 32 with and 68 without can be used for constructing a neovagina. Especially in vaginal stenosis was the most frequently (45%) as Mayer-Rokitansky-Kuster-Hauser (MRKH) cases where no redundant penile and/or scrotal skin is encountered complication and it was noted in all (three additional FTG), none of the tested parameters syndrome) and those who underwent vaginectomy out of three) of the patients who were reconstructed by (patient-reported esthetic outcome, overall satisfaction available for grafting, intestinal grafts provide a good due to gynecological malignancy or trauma. with the neovagina, sexual function and genital image) alternative. Some authors used 7 cm as the cut-off for STG alone differed significantly between the two groups. Recently, penile skin length below which bowel-based options Vaginoplasty techniques Papadopulos et al. assessed the surgical outcome of should be offered (Buncamper et al.) A lack of penile 2. Penile skin inversion technique Different nonsurgical and surgical techniques have and scrotal skin is often present in transwomen who Penile skin inversion technique remains the method of their combined vaginoplasty technique in which been developed and utilized for the purpose to spatulated urethra together with a scrotal skin graft started hormonal therapy (puberty blockers) at a choice for vaginoplasty in MTF transition. Its origin reconstruct a normal functioning vagina with a was used in addition to the penile skin flap to form the younger age. Pedicled bowel segments can also be dates back to 1957, when Gillies and Millard reported satisfactory sexual function and appearance for these on the use of penile skin as a pedicled flap for the neovagina. The main aim of this procedure was to used when prior neovaginal reconstructive attempts patients. achieve the largest possible vaginal depth and width, with skin flaps and/or grafts failed in transgender vaginal lining. Later on, Burou popularized the utility increasing the lubrication level of the neovagina and patients. The need to elongate the vagina in of anteriorly pedicled providing a more esthetic mons pubis by decreasing transwomen requiring greater depth after a previous penile skin flaps for the the abdominal tension that might be more pronounced neovaginal construction is another indication to inversion technique. where solely penile skin was used for reconstruction. proceed with intestinal vaginoplasty.

Currently, penile skin inversion technique is the They also created a “clitoral hood” with an esthetic prepuce by dividing the foreskin into an inner and Use of pedicled bowel segments offers some most frequently advantages regarding cosmesis and sexual function. performed and hence the outer layer in an effort to prevent clitoral desensitization. Measured postoperative neovaginal First of all, it provides sufficient amount of tissue for most extensively studied surgical procedure within depth ranged from 11,77 to 14,99 cm, depending on the optimal vaginal depth and width. Moreover, this tissue the context of MTF gender size of the dilator used (25-40 mm). All of the patients is self-lubricating given the secretory potential of the intestinal mucosa. Additionally, intestinal inner lining reassignment. Herein; the further reported intact and favorable vaginal, clitoral resembles the vaginal mucosa in texture and inverted penile skin on an and labial sensitivities. appearance. Lastly, the lumen of the isolated intestinal abdominal or more segment has little tendency to shrink which eliminates inferior pedicle is used as Denonvillier’s fascia should be opened to create a space for the neovagina. Dissection should be carried the need for lifelong postoperative vaginal dilatation an outside-in skin tube out up to the level of pouch of Douglas superiorly and which is almost always necessary in non-intestinal for the lining of the ischial spines laterally. This type of extended dissection graft/flap based neovaginal constructions (Bouman et neovagina (Bizic et al., of the rectoprostatic space allows for omission of al., DeMarco et al.). Intestinal vaginoplasty has also Horbach et al.). sacrospinal fixation, thus preventing damage to the some inherent disadvantages such as; the need for intestinal anastomosis, the risk of postoperative Preserved vascularization pudendal neurovascular bundle (Kocjancic et al.).

Inadvertent rectal injuries can occur during the of the penile skin, its Figuur 1: Penile skin inversion Continued on page 15 development of this space and may lead to fistula mobility, non-hair14

EUT Congress News

Saturday, 17 March 2018

Managing complex cases in functional urology How many drugs my BPH/BPE patients may need to control LUTS? Dr. Frank Van der Aa Functional and Reconstructive Urology Neurourology Department of Urology UZ Leuven Leuven (BE)

Male lower urinary tract symptoms (LUTS) are an increasingly frequent encountered symptom complex.

Due to the increased life expectancy and the high quality of life, people seek improvement or cure for LUTS. The majority of male LUTS is still caused by benign prostatic hyperplasia (BPH). Mostly, but not always BPH is associated with benign prostatic enlargement (BPE). When patients seek help for invalidating LUTS due to BPH, the treating clinician should elucidate certain elements in order to select the right treatment for the right patient.

For current medical LUTS treatment, one can choose between several medications. When considering medical LUTS treatment, one should take into account the risk of progression of the underlying BPH, the invalidating nature of the symptom complex, the predominant symptom(s), the risk of side effects and the cost of the treatment2.

Prior to considering treatment, it is evident that symptoms should be bothersome for the patient.

Patients with light to moderate symptoms should be reassured and given lifestyle advice3.

The risk of progression is easily defined as increasing LUTS (for the majority of patients). In a subset of patients, acute urinary retention (AUR) and need/ demand for surgical treatment define progression.

Patients who are at risk for progression, might benefit from hormonal treatment with 5 alpha-reductase inhibitors since this treatment has a well proven risk reduction for surgery and AUR. Certainly when comorbidities put the patient at risk for surgical treatment, this treatment should be offered. Easily detectable risk factors for progression are patient age, prostate volume, PSA level and presence of PVR4.

LUTS due to BPH are a combined symptom complex, often presenting with voiding and with storage symptoms, with day- and nighttime symptoms and there is a known association with erectile dysfunction. When patients present with a combination of these symptoms, it is a normal reflex to prescribe medications that treat the different aspects of the symptom complex. A second reason is to have a faster and stronger response by combining different working mechanism to treat BPH-related LUTS.

An example is the direct relaxing effect on smooth muscle from alphablocking agents combined Firstly, the clinician should confirm that the patient Voiding symptoms is suffering from uncomplicated BPH related LUTS. with the slow but The nature of the symptom complex will determine sustained effect on The functional lower urinary tract disorder should the medical treatment. The majority of patients will not be associated with complications of the lower have voiding symptoms as part of male LUTS. Voiding prostate stroma and gland tissue of 5-alpha-reductase urinary tract (such as high PVR, bladder stones, symptoms in the presence of a small prostate will bladder diverticula, recurrent bleeding and direct the clinician to the use of alpha-blocking agents inhibitors. Another recurrent infections) or complications of the upper example is the combination or phosphodiesterase-5 inhibitors. The presence of urinary tract (such as hydro-ureteronephrosis, renal storage symptoms will direct the clinician to treatment of alpha-blocking agents function deterioration or ascending urinary tract with antimuscarinic agents or beta-3-adrenoreceptor with antimuscarinics to Most male LUTS is caused by benign prostatic hyperplasia (BPH) which, in turn, is linked to infections). These cases mandate (surgical) treat both prostate/bladder benign prostatic enlargement (Photo: Getty Images) agonists. Depending on the size of the prostate, also neck and detrusor muscle treatment. hormonal therapy with 5-alpha-reductase inhibitors in patients with can be considered. In the case of bothersome In the case of uncomplicated BPH-related LUTS, predominant storage LUTS. nocturia, desmopressin could be an option.

Both above mentioned combinations are also patients generally prefer medical treatment over recommended by the EAU guidelines. After surgical treatment. In the last decades, the incidence There are several reasons to combine different agents Unfortunately, there are also downsides on monotherapy, these combinations are the most combination therapy. First of all, the combination of of surgical treatment for BPH-related LUTS has of the above-mentioned treatment options in one frequently prescribed medications12. significantly declined. The incidence of medical patient. A first reason is to tackle the different aspects several active components not only increases efficacy but also comes with an increased rate and spectrum treatment however has increased significantly1. of the symptom complex.

There is limited but promising evidence for some of side effects. Secondly, taking more than one pill a other dual combinations, such as alpha-blocking day increases the likelihood of intake errors and of agents with phosphodiesterase-5 inhibitors and adherence problems. Fixed dose combinations, phosphodiesterase-5 inhibitors with 5-alphacombining two active ingredients in one tablet reductase inhibitors13,14.

Update in vaginoplasty... Continued from page 14 derived vaginoplasties, respectively). Introital diminish these problem5. In some healthcare settings, stenosis, necessitating revision surgery, was the the price of combination therapy might be high for bowel-related complications (ileus, anastomosis leak, main postoperative complication and this was seen Triple combinations are not studied. In prevalence peritonitis etc.), excessive mucus production, introital in 4.1% and 1.2% of the sigmoid-derived and the average level income earner. studies, only a marginal number of patients is on stenosis, bleeding after intercourse, malodor and ileum-derived vaginoplasties, respectively (Bouman triple therapy for BPH related LUTS. This number although anecdotal the potential for developing et al.). The rate of sexual satisfaction, which was Paradoxically, combination therapy can also might be underestimated. Patients might take, for usually assesed in a subjective fashion and without counteract some of the side effects. The sexual side diversion colitis, ulcerative colitis and cancer. example, short acting phosphodiesterase-5 inhibitors the use of Female Sexual Function Index (FSFI), was effects of alpha blocking agents or 5-alpha-reductase for erectile dysfunction or desmopressin for nocturnal The basic steps of intestinal vaginoplasty can be reported to be 85.7% (Davies et al., Hensle et al.). inhibitors can theoretically be attenuated by polyuria, besides combination therapy for BPHphosphodiesterase inhibitors, for example6. summarized as; harvest of the intestinal segment related LUTS. (through median or Pfannenstiel laparotomy, Integrated multidisciplinary approach laparoscopy-assisted laparotomy and total Gender dysphoria and patients complaining about Dual combination thearapies It has to be emphasized that no evidence exists for laparoscopy), perineal incision, dissection of the this disorder have started to gain wider acceptance There is strong evidence for dual combination triple therapy. A clinician prescribing more than the neovaginal cavity, perineal-vaginal-bowel by the community which translated into increased therapies. The best studied combination consists of well-studied dual combination therapies, should warn anastomoses and neovaginal fixation to prevent number of patients engaging into this transition and alpha blocking agents combined with 5-alphathe patient on possible side effects and interactions. prolapse (Bouman et al.). Sigmoid colon and ileum are seeking for treatment. Authorities and global reductase inhibitors. Since more than 10 years, level 1 the most commonly preferred intestinal segments for organizations have established standards related evidence exists. Several prospective randomized Combination therapy offers benefits vaginoplasty. Sigmoid colon possesses the advantages with the diagnosis and management (medical and controlled trials have been conducted and have In conclusion, combination therapy is a recognized of having a thicker wall, larger diameter, better surgical) of gender dysphoria which requires an shown both an additive effect of the dual therapy on and well-taken option for BPH related LUTS. Probably tolerance to trauma and more similarities to the integrated multidisciplinary approach. Vaginoplasty symptom relief as a decreased risk for disease about one in five to one in four patients is treated vaginal lining in terms of appearance, texture and represents the last step of the MTF transition progression in the long run7,8. with combination therapy, mostly 5-alpha-reductase natural lubrication (Colebunders et al.). Despite being process. Penile skin inversion technique is the most inhibitors with alpha-blocking agents and, secondly, stated as an advantage of intestinal segments, mucus investigated and therefore the most evidence-based It is important to realize that this combination therapy antimuscarinics with alpha-blocking agents. production may lead to excessive discharge and be the technique for vaginoplasty. Surgical outcome and Combination therapy offers advantages in onset and should only be offered to patients with a certain cause of malodor, especially when ileum is used. sexual function associated with this technique are magnitude of effect of symptom relief in patients with prostate volume. Alpha-blocking agents will have an generally acceptable to good. Using additional BPH-related LUTS. Increased costs and side effects are immediate effect voiding symptoms, whereas Laparoscopic harvest of the bowel for vaginoplasty was urethral and penoscrotal flaps may provide benefit 5-alpha-reductase inhibitors will result in a decreased the down side of this treatment option. introduced in order to minimize the inevitable in terms neovaginal depth and lubrication. prostate volume in the long run. The total symptom morbidity associated with open transperitoneal Intestinal vaginoplasty is a viable alternative, The key lies in selecting the appropriate patients for a improvement with the combination treatment is surgery. The length of harvested segments vary especially for secondary procedures. Overall, the specific combination treatment. In this way, the higher than the symptom relief achieved by either considerably, ranging from 7,5 cm to 20 cm. Different outcome of vaginoplasty with pedicled bowel benefit outweighs the risks. Combining more than monotherapy. It is not useful to prescribe 5-alphafolding techniques (U-pouch, J-pouch, detubularization segments does not seem to be inferior to the penile two medications is not well-studied and is probably reductase inhibitors if the patent is not motivated to and retubularization technique) can be utilized to skin inversion technique. There is a need for not often done in real-life practice. In difficult-to-treat take the medication for at least six months. create a neovaginal pouch. Depending on the vascular prospective randomized studies with standardized patients with persisting symptoms, it can be anatomy of the patient, the intestinal graft can be considered at an individual patient level. The patients surgical procedures, larger patient cohorts and The down side of combination treatment is the has to be warned about possible interactions and transferred to the perineum in an isoperistaltic or longer follow-up period in order to make a valid increased risk of side effects associated with antiperistaltic fashion to minimize the tension on the increased risk for side effects. Cost might also be comparison between the available vaginoplasty prescribing two active components with different vascular pedicle (Bouman et al.). Usually a two-finger- techiques and identify the â&#x20AC;&#x153;idealâ&#x20AC;? one. high. working mechanisms. It is generally believed that, if wide space between rectum and urethra is created by side effects occur, they are reversible after therapy blunt dissection. Fixing the neovagina to the sacral Editorial Note: Due to space constraints, the cessation9. Adequate patient selection is key for Editorial Note: Due to space constraints, the promontory, the uterosacral ligament and adjacent reference list can be made available to interested having a good benefit-risk ratio. reference list can be made available to interested muscle fascia of the pelvic floor are the commonly readers upon request by sending an email to: readers upon request by sending an email to: Alpha-blocking agents combined with antimuscarinics communications@uroweb.org applied maneuvers to prevent prolapse (Bouman et al., communications@uroweb.org is a second well-studied dual combination treatment Moudouni et al. Karateke et al.).

Saturday 17 March in male LUTS patients with predominant or residual Saturday 17 MSaturday 17 March In a recent review, which included 21 retrospective 10.15-15.35: Meeting of the EAU Section of storage symptoms. There exists level 1 evidence that 10.15-14.00: Meeting of the EAU Section of studies and 894 patients, the prevalence and Genito-Urinary Reconstructive Surgeons in male patients with a minimum threshold storage Female and Functional Urology (ESFFU), severity of periprocedural complications were (ESGURS); Updates in genito-urinary symptoms, a fixed dose combination of an alphaManagement of complex cases in male and reported to be low after intestinal vaginoplasty reconstruction blocking agent with an antimuscarinic improves the female functional urology (6.4% and 8.3% for sigmoid-derived and ileumresponse in comparison to monotherapy10,11.

Saturday, 17 March 2018

EUT Congress News

15

Residual fragments - an ongoing headache after fURS Patient follow-up and counselling are crucial in renal stone cases Prof. Dr. Arkadiusz Miernik Dept. of Urology Medical Centre University of Freiburg Freiburg (DE)

The surgical treatment of urolithiasis has evolved substantially over the last three decades. Open surgery has been replaced by endoscopic techniques. In addition, new disintegration energy sources such as holmium laser lithotripsy gained supremacy in endourological theaters. The role of shock wave lithotripsy (SWL) has been decreasing, however.

Figure 1: High-risk (A) and low-risk (B) stone formers with (green line)/without RF (blue line) (according to Hein et al. 2016)3

The widespread use of SWL led to the introduction of the term “clinically insignificant residual fragments” (CIRF) to urological vocabulary. These stone fragments are defined as post-lithotripsy disintegrates measuring 4mm or less in diameter. From the practical perspective, it is assumed that these fragments pass spontaneously through the urinary tract without causing the patient any clinically relevant conditions.

Residual fragments (RF) may also remain in the collecting system after any kind of surgical intervention also, especially after shock wave lithotripsy (SWL), percutaneous litholapaxy (PCNL), and retrograde intrarenal surgery (RIRS).

In recent years a shift has occurred worldwide towards RIRS as represented by flexible ureteroscopy (fURS) in combination with laser lithotripsy. fURS enables relatively “straightforward” and rapid access to the upper urinary tract, allowing the endourologist to inspect all its areas and target stones easily.

This trend is affecting both the absolute number of fURS procedures for urolithiasis-related interventions and stone size. Large renal stones (LRS) also tend to be treated by RIRS. Because of the retrograde route’s anatomical limitations, namely a relatively thin ureter diameter and access sheaths (UAS) smaller than those used in PCNL, LRS extraction can become very time-consuming. To overcome this obstacle, several disintegration concepts have been developed. One recommends the creation of very small pieces (of stone dust, or sand) that pass spontaneously after treatment1.

Our study’s most important finding was that 33.3% of the low-risk stone patients with RFs after RIRS experienced an ipsilateral SRE, while low-risk individuals with no RFs suffered no SRE on the ipsilateral side (p < 0.001).

significant ergonomic improvements. Conventional master-slave systems for laparoscopic surgery in urology such as DaVinci® might also prove useful for stone retrieval, particularly for large and very large renal and ureteric calculi2.

After the initial euphoria that accompanied the introduction of highly miniaturized endoscopic instruments and advanced lithotripsy systems allowing safe, rapid, and precise treatment of urinary stones, the long-underrated problem of RFs might indeed give the endourologist a headache.

Residual fragments are clinically important There is now high quality evidence and knowledge regarding RF after RIRS that confirm that RFs are clinically important. They affect significantly the patient’s post-interventional clinical course. Low-risk stone formers benefit especially from complete stone clearance. Differences between patients with or without RF become apparent over the long term, probably due to a delayed Nidus effect in recurrent stone formation. The term “clinically insignificant rest fragments” (CIRF) should therefore be abandoned.

There is now evidence that endoscopically-determined RFs are an independent predicting factor for SRE in low-risk stone formers, and that they threaten the postoperative course especially over longer follow-up periods. Thus every effort must be made to achieve complete stone clearance after endoscopic interventions and SWL to treat upper urinary tract urolithiasis. Patients presenting RF are at risk for (ipsilateral) SREs requiring medical and/or surgical interventions.

The lessons we learned from this evidence are that: • the current surgical management of urinary stones should always aim for total stone clearance, and • that patients with miniscule RFs should not be declared stone-free.

What has the future in store for us?

Admittedly, little is known about the natural history and Several technical improvements have been validated in vitro and in small case series. SWL technology is clinical relevance of RF on patients’ course or their impact on subsequent stone-related events (SRE). Little providing new camera systems for continuous has been published on long-term outcomes, and the monitoring of SWL head coupling during the evidence level in what has been reported is low. Most procedure, which might significantly decrease the publications discuss case series, and even the RF number and energy levels of shockwaves to achieve definition (size, detection) and follow-up strategies are comparable results and high stone-free rates. quite heterogeneous. In the literature, the postoperative Publications addressing new lens designs have also observation of patients with RF ranges from 15 months reported greater focusing precision and efficacy. to 4.9 years. More interesting, are retreatment rates Interestingly, a novel technology described as ‘burst between 19.6 and 58.6% during follow-up2. wave lithotripsy’ might also enhance SWL’s efficacy.

Status quo Is the presence of RS after stone interventions a reason to worry? Several investigations were conducted to answer this question. Our group assessed stonerelated events (SRE) requiring retreatment in a series of 100 consecutive patients treated by RIRS for renal stones and evaluated potential risk factors thereof3. We defined RF as fragments measuring <1mm (i.e., fragments too small for retrieval). Our primary outcome was the incidence of SRE requiring medical or surgical treatment during the follow-up period. The secondary parameters we investigated were SRE, time to SRE, and late complications.

To distinguish between RF related conditions and metabolic factors, our follow-up cohort was stratified into low- and high-risk stone formers. We also considered obesity, high stone burden, and lower pole stones as independent parameters, and included those data in our statistical evaluation.

Mean follow-up was 59 months (31–69) in 85 out of 99 patients, among whom 26 (30.1%) suffered an SRE. Thirty-four of the 85 (40%) patients were high-risk stone formers. Twenty-two of them experienced SREs (both sides) during follow-up (64.7%, p < 0.001). Eight of the 17 patients (47.1%) with SRF experienced an SRE on the ipsilateral side, compared with 13 (19.1%) of the 68 without SRF (p = 0.022, hazard ratio 2.823, 95% confidence interval [95% CI] 1.16, 6.85). Risk for an ipsilateral SRE was unaffected by the presence of SRF among HRSFs p = 0.561).

16

EUT Congress News

The awareness that RF may not always be avoidable means that conscientious patient follow-up and counselling are extremely important in case of RS after treatment.

Some interesting future developments should be discussed concerning the RIRS techniques now leading among the modalities applied in modern stone therapy.

First, innovations in disintegration technology are most welcome and important if RFs are to be avoided.

Present-day Ho:YAG lasers are the gold standard in endoscopic lithotripsy in both RIRS and PCNL. The latest technological innovations are aiming for safer and faster disintegration achieving similarly-sized fragments. Holmium laser devices now offer higher energy and frequencies, but also longer pulses, causing less retropulsion and producing smaller fragments (dust, stone sand).

Second, we need better retrieval instruments such as graspers and baskets. The size of novel endoscopic instruments requires new concepts and designs of extraction devices. New grasper designs cannot be simply adopted from open stone surgery or semi-rigid ureteroscopy for ureteral fragments. Ultimately, completely new RIRS approaches need to be developed. These include irrigation and suction devices, gluing agents, magnetic extractors, etc.

Last but not least, the slow fusion of flexible ureteroscopy with master-slave robotic platforms is currently a hot topic, similar to urologic laparoscopy.

Several robotic systems for urolithiasis therapy have been introduced. Despite some limitations in the active extraction of stone fragments, these solutions offer

References 1. De la Rosette J, Denstedt J. Update from third international consultation on stone disease. Springer; 2017.

2. Hein S, Miernik A, Wilhelm K, Adams F, Schlager D, Herrmann TR, et al. Clinical significance of residual fragments in 2015: impact, detection, and how to avoid them. World Journal of Urology.

2016;34(6):771-8.

3. Hein S, Miernik A, Wilhelm K, Schlager D, Schoeb DS, Adams F, et al. Endoscopically determined stone clearance predicts disease recurrence within 5 years after retrograde intrarenal surgery. Journal of Endourology.

2016;30(6):644-9.

Saturday 17 March 10.15-14.30: Meeting of the EAU Section of Urolithiasis (EULIS) Management of stones: Advancing technology, increasing experience and changing concepts.

Where are we in 2018?

IPSEN SATELLITE SYMPOSIUM 2018, 33 RD ANNUAL EAU CONGRESS, COPENHAGEN

Optimising patient management in urogenital cancers Date: 18:00–19:30, Saturday 17 March 2018 Venue: Green Area, Room 2 (Level 0), Bella Center, Copenhagen Chaired by Dr Maria Ribal (Spain) Agenda Time

Topic

Speaker

18:00–18:05

Welcome and introduction

Dr Maria Ribal

18:05–18:30

The significance of testosterone and gonadotropin suppression in advanced prostate cancer treatment

Dr Peter Busch Østergren

18:30–18:55

Predicting the future of PDD – blue skies or dark clouds

Pr Morgan Rouprêt

18:55–19:20

Current strategies and future challenges in 2nd line therapy in advanced RCC

Pr Petri Bono

19:20–19:30

Discussion and closing remarks

Dr Maria Ribal

The management of patients with urogenital cancers continues to advance, driven by the release of new clinical data and the progression of available interventional and imaging techniques. For the treatment of prostate cancer, hormone manipulation remains a key therapeutic strategy. Recent data has provided new insights on the impact of androgen deprivation therapy on testosterone levels, compared with subscapular orchiectomy in patients with advanced disease.

detection. In addition, new optical diagnostic tools can provide real-time information on tumour invasiveness and grade to help differentiate tumour types and guide treatment decisions.

Finally, the treatment landscape of 2nd line advanced renal cell carcinoma (aRCC) has evolved rapidly during recent years, with data from clinical trials investigating the impact of targeted therapies and immuno-oncology agents. The availability of new Advancements in imaging techniques have been crucial for improving agents and changes to treatment guidelines have optimised management of patients with non-muscle-invasive bladder cancer. management for patients with aRCC. Techniques such as photodynamic diagnosis (PDD), play a key role This meeting is initiated and funded by Ipsen. in identifying suspect lesions, which may result in increased tumour

Please visit the Ipsen booth E15 CBZ-ALL-000560 13 February 2018

Saturday, 17 March 2018

t e all i s th h i V in n o i s t 7 i u ib 5 E h h Ex oot B

TOOKAD® (padeliporfin)

Vascular Targeted Photodynamic Therapy1 Marketing Authorization (EMA) granted by European Commission November 10th 20172

Together Created by Steba Biotech from ref. 5

Non Thermal Light3

SYMPOSIUM

padeliporfin4

Date & Time: Location:

Sunday March 18 17:45 – 19:15 Blue Area, Room 5 (Level 0)

Chairman: M. Wirth, Dresden (DE) M. Wirth, Dresden (DE) Welcome 17:45 - 17:50

F. Montorsi, Milan (IT) Clinical Results (Ph. III) 17:50 - 18:10

I.S. Gill, Los Angeles (US) Active surveillance & TOOKAD® 18:10 - 18:30

A. Scherz, Rehovot (IS) Focal Therapy & Non thermal light 18:30 - 18:50

A.R. Azzouzi, Angers (FR) Procedure & Practical training 18:50 - 19:10

M. Wirth, Dresden (DE) Conclusion 19:10 - 19:15

TOOKAD (padeliporfin) 183 mg or 366 mg powder for solu�on for injec�on Abbreviated prescribing informa�on – please consult the full summary of product characteris�cs before prescribing. ▼ This medicinal product is subject to addi�onal monitoring. This will allow quick iden�fica�on of new safety informa�on. Healthcare professionals are asked to report any suspected adverse reac�ons.

Therapeu�c indica�ons: TOOKAD is indicated as monotherapy for adult pa�ents with previously untreated, unilateral, low-risk, adenocarcinoma of the prostate with a life expectancy ≥ 10 years and: Clinical stage T1c or T2a, - Gleason Score ≤ 6, based on high-resolu�on biopsy strategies, - PSA ≤ 10 ng/mL, - 3 posi�ve cancer cores with a maximum cancer core length of 5 mm in any one core or 1-2 posi�ve cancer cores with ≥ 50 % cancer involvement in any one core or a PSA density ≥ 0.15 ng/mL/cm3.

Posology and method of administra�on: TOOKAD is restricted to hospital use only. It should only be used by personnel trained in the Vascular-Targeted Photodynamic therapy (VTP) procedure. The recommended posology of TOOKAD is one single dose of 3.66 mg/kg of padeliporfin. TOOKAD is administered as part of focal VTP. The VTP procedure is performed under general anaesthe�c a�er rectal prepara�on. Prophylac�c an�bio�cs and alpha-blockers may be prescribed at the physician’s discre�on. Retreatment of the same lobe or sequen�al treatment of the contralateral lobe of the prostate are not recommended.

Special populations. In pa�ents with severe hepa�c impairment TOOKAD should be used with cau�on.

In pa�ents with renal impairment or in elderly pa�ents no dose adjustment is needed. This medicinal product contains potassium. Illumination for photoactivation of TOOKAD. The solu�on is administered by intravenous injec�on over 10 minutes. Then the prostate is illuminated immediately for 22 minutes 15 seconds by laser light at 753 nm delivered via inters��al op�cal fibres from a laser device at a power of 150 mW/cm of fibre, delivering an energy of 200 J/cm. Treatment should not be undertaken in pa�ents where a Light Density Index (LDI) ≥ 1 cannot be achieved. See the SmPC for further instruc�ons.

Contraindica�ons Hypersensi�vity to the ac�ve substance or to any of the excipients. Any previous prosta�c interven�ons where the internal urinary sphincter may have been damaged, including trans-urethral resec�on of the prostate (TURP) for benign prosta�c hypertrophy. Current or prior treatment for prostate cancer. Pa�ents who have been diagnosed with cholestasis. Current exacerba�on of rectal inflammatory bowel disease. Any medical condi�on that precludes the administra�on of a general anaesthe�c or invasive procedures.

Special warnings and precau�ons for use: Tumour localisation. Before treatment, the tumour must be accurately located and confirmed as unilateral using high-resolu�on biopsy strategies based on current best prac�ce, such as mul�-parametric MRI-based strategies or template-based biopsy procedures.

Simultaneous treatment of both prostate lobes was associated with an inferior outcome in clinical trials and should not be performed. Insufficient pa�ents underwent retreatment of the ipsilateral lobe or sequen�al treatment of the contralateral lobe to determine the efficacy and safety of a second TOOKAD-VTP procedure. Follow-up post TOOKAD-VTP. There is limited biopsy data beyond 2 years a�er TOOKAD treatment, so long-term efficacy has not been determined. Residual tumour has been found on follow-up biopsy of the treated lobe at 12 and 24 months, usually outside of the treated volume, but occasionally within the area of necrosis. There is limited data on long-term outcomes and on poten�al consequences of post-TOOKAD local scarring in case of disease progression. At present TOOKAD-VTP has been shown to defer the need for radical therapy and its associated toxicity. Longer follow-up will be required to determine whether TOOKAD-VTP will be cura�ve in a propor�on of pa�ents. Following TOOKAD VTP, pa�ents should undergo digital rectal examina�on (DRE) and have their serum PSA monitored, including an assessment of PSA dynamics (PSA doubling �me and PSA velocity). PSA should be tested every 3 months for first 2 years post VTP and every 6-months therea�er in order to assess PSA dynamics (PSA Doubling Time (DT), PSA velocity). Digital Rectal Examina�on (DRE) is recommended to be performed at least once a year and more o�en if clinically jus�fied. Rou�ne biopsy is recommended at 2-4 years and 7 years post VTP, with addi�onal biopsies based on clinical/ PSA assessment. Radical therapy post VTP procedure. Limited informa�on is available regarding the safety and efficacy of radical prostatectomy a�er TOOKAD-VTP. Photosensitivity. There is a risk of skin and eye photosensi�vity with exposure to light post TOOKAD-VTP. It is important that all pa�ents follow the light precau�ons for 48 hours post-procedure to minimize the risk of damage to the skin and eyes.

Pa�ents should avoid exposure to direct sunlight (including through windows) and all bright light sources, both indoors and outdoors. For specific instruc�ons on light protec�on measures, see the SmPC sect. 4.4. Erectile dysfunction. Erec�le dysfunc�on may occur even if radical prostatectomy is avoided. Some degree of erec�le dysfunc�on is possible soon a�er the procedure and may last for more than 6 months. Extra-prostatic necrosis. There may be extraprosta�c necrosis in the peri-prosta�c fat.

Excessive extraprosta�c necrosis occurred as a result of incorrect calibra�on of the laser or placement of the light fibres. In consequence there is a poten�al risk of damage to adjacent structures, such as the bladder and/or rectum, and development of a recto-urethral or external fistula. A urinary fistula has occurred in one case due to incorrect fibre placement. The equipment should be carefully calibrated and use the treatment guidance so�ware to reduce the risk of clinically significant extraprosta�c necrosis.

Urinary retention/urethral stricture. Pa�ents with a history of urethral stricture or with urinary flow problems may be at increased risk of poor flow and urinary reten�on post the TOOKAD-VTP procedure.

Urinary incontinence. The risk of sphincter damage can be minimised by careful planning of the fibre placement using the treatment guidance so�ware. The TOOKAD-VTP procedure is contraindicated in pa�ents with any previous prosta�c interven�ons where the internal urinary sphincter may have been damaged. Inflammatory bowel disease. TOOKAD-VTP should only be administered a�er careful clinical evalua�on, to pa�ents with a history of ac�ve rectal inflammatory bowel disease or any condi�on that may increase the risk of recto-urethral fistula forma�on. Use in patients with abnormal clotting.

Pa�ents with abnormal clo�ng may develop excessive bleeding due to the inser�on of the needles required to posi�on the light fibres.

Interac�ons: The use of medicinal products that are substrates of OATP1B1 or OATP1B3 (repaglinide, atorvasta�n, pitavasta�n, pravasta�n, rosuvasta�n, simvasta�n, bosentan, glyburide) for which concentra�on-dependent serious adverse events have been observed should be avoided on the day of TOOKAD infusion and for at least 24 hours a�er administra�on. Medicinal products which have poten�al photosensi�sing effects (such as tetracyclines, sulphonamides, quinolones, phenothiazines, sulfonylurea hypoglycaemic agents, thiazide diure�cs, griseofulvin or amiodarone) should be stopped at least 10 days before the procedure with TOOKAD and for at least 3 days a�er the procedure.

An�coagulant medicinal products and those that decrease platelet aggrega�on (e.g. acetylsalicylic acid) should be stopped at least 10 days before the procedure with TOOKAD. Medicinal products that prevent or reduce platelet aggrega�on should not be started for at least 3 days a�er the procedure.

Fer�lity, pregnancy and lacta�on: Contraception. If the pa�ent is sexually ac�ve with women who are capable of ge�ng pregnant, he and/or his partner should use an effec�ve form of birth control to prevent ge�ng pregnant during a period of 90 days a�er the VTP procedure. Pregnancy and breastfeeding. TOOKAD is not indicated for the treatment of women.

Effects on ability to drive and use machines: TOOKAD has no influence on the ability to drive or use machines.

Undesirable effects: Very common (≥ 1/10): Urinary reten�on, haematuria, dysuria, micturi�on disorders, perineal pain, male sexual dysfunc�on. Common (≥ 1/100 to < 1/10): Genito-urinary tract infec�on, haematoma, hypertension, haemorrhoids, anorectal discomfort, abdominal pain, rectal haemorrhage, hepatotoxicity, ecchymosis, back pain, urethral stenosis, urinary incon�nence, prosta��s, genital pain, prosta�c pain, haematospermia, fa�gue, abnormal clo�ng, perineal injury. For undesirable effects with an incidence lower than 1/100, please refer to the SmPC. Overdose: Limited informa�on. A prolonga�on of photosensi�sa�on is possible and precau�ons against light exposure should be maintained for an addi�onal 24 hours. An overdose of the laser light may increase the risk of undesirable extraprosta�c necrosis.

Prescrip�on status: BEGR Packages: 183 mg, powder for solu�on for injec�on, 1 vial; 366 mg, powder for solu�on for injec�on, 1 vial. The price will be published at www.medicinpriser.dk, when the product is on the market.

The Prescribing Informa�on (FEB2018) has been rewri�en and/or abbreviated as compared to the European Medicines Agency approved SmPC (NOV2017), which can be requested free of charge from the Marke�ng Authoriza�on Holder: Steba Biotech S.A., 7 Place du Théâtre, L-2613 Luxembourg, Luxembourg. info@stebabiotech.com

Adverse events can be reported to steba@primevigilance.com

1 - SmPC TOOKAD®. European Medicines Agency November 2017 2 - Community register of medicinal products for human use: http://ec.europa.eu/health/documents/community-register/html/h1228.htm#EndOfPage 3 - Azzouzi et al. Lancet Oncol. 2017 Feb;18 (2): 181-191 4- WHO Drug Information, Vol. 20, No. 4, 2006 5 - Azzouzi et al. World J Urol. 2015; 33:937-944

Saturday, 17 March 2018

www.stebabiotech.com | Info@stebabiotech.com

EUT Congress News

17

Is TURP safe in frail elderly men or is MIT better?

Minimally invasive treatment (MIT) is recommended for frail elderly patients but studies are needed Prof. Andrea Tubaro Department of Urology Sapienza University of Rome Rome (IT)

Table 1: Morbidity and Mortality of BPE surgery in elderly patients Authors

Reich et al.

Matani et al.

Co-Author: F. Presicce, Rome (IT) The medical treatment of lower urinary tract symptoms (LUTS) secondary to benign prostatic enlargement (BPE) is certainly a successful story in the field of urology.

During the last two decades, the introduction of several pharmaceutical agents has dramatically decreased the rates of BPE surgery all over the world and has significantly postponed its indication over time.

In addition, an increase in life expectancy associated with an increasing proportion of elderly men in general population results in more octogenarians presenting bothersome LUTS, refractory to medications, requiring prostate surgery. Thus, the clinical scenario for prostate surgery is evolving: nowadays patients, who undergo BPE surgery, may be generally older, with more severe comorbidities and with larger prostates, possibly necessitating more challenging procedures.

The difference between adult and frail elderly patients is fourfold: aging per se is considered a risk factor for surgery, aging is associated with comorbidities, aging is associated with larger prostate volumes and aging patients have a limited life expectancy so that durability of the treatment effect can be of different importance.

For years, transurethral resection of the prostate (TURP) has been considered the gold standard for the relief of prostate outlet obstruction (BPO) secondary to BPE. In fact, as shown by several evidences in the literature, TURP provided a high rate of efficacy and long-term durability with an acceptable number of complications.

However, these data are mainly extrapolated from multicenter studies and meta-analyses with the vast majority of patients generally approximately 65 to 75 years old. Unfortunately very few studies, in general dated and with several methodological bias, specifically addressed the efficacy and safety profile of TURP in over 75 years old patients.

On the other hand, several minimally invasive procedures for treating BPE [i.e.: vaporization with 532 nm Greenlight Laser, Holmium/Thulium Laser Enucleation (HoLEP/ThuLEP), Prostatic Urethral Lift (Urolift®), Prostate artery embolization (PAE)] have been developed in recent years. Preliminary experiences with these techniques suggest a shorter hospitalization, a reduced number of complications and, for some of these methods, even the possibility of performing them as day-cases and with no need for general anaesthesia. The lower morbidity and the higher safety profile of these procedures compared to TURP could make them a particular attractive option in frail elderly men. However, as well as for TURP, very few studies have specifically assessed the safety of these methods in frail elderly patients and head-tohead comparison studies with the TURP on this particular population are not available.

Morbidity and perioperative outcomes In this report, we collected the existing evidences about morbidity and perioperative outcomes of different techniques for treatment of BPE among frail elderly patients. In 2008 Reich et al prospectively evaluated morbidity, mortality and early outcome of TURP in more than 10,000 patients. The mean age of the enrolled population was 71.1 years old, the mortality rate was 0.1% and the overall morbidity was 11.1%. The most common complications during the first month were urinary catheter withdrawal failure (5.8%), reintervention (5.6%), symptomatic urinary tract infections (3.6%), bleeding requiring transfusions (2.9%), and TURP syndrome (1.4%). Reich et al did not focus their attention towards frail elderly men in their study; however morbidity was significantly increased by age, polymedication, and preoperative indwelling catheter. This study has been considered the milestone with which to compare other studies on the same topic due to the sample size and the accuracy with which it was carried out.

Country and Study Interval

N° of enrolled patients Germany, 2002-2003 10654

Germany, 1996

166

Age at inclusion (Years) -

> 80

Mean Age (Years) 71

82

Surgery Technique performed TURP

TURP

Morbidity (%)

Mortality Comments and Limitations (%)

11.10

0.10

Strength: Good sample size, prospective design.

1.20

Limitations: No qualitative assessment of ageing status, not focused on elderly patients.

Strength: Good sample size.

26

Wyatt et al.

UK, 1989

94

> 80

-

TURP

71

5

Brierly et al.

UK, 1993-1997

90

> 80

84

TURP

39

0

Mebust et al.

US, 1978-1987

472

> 80

-

TURP

22.60

0.20

Limitations: No qualitative assessment of ageing status, retrospective design.

Limitations: No qualitative assessment of ageing status, retrospective design.

Limitations: No qualitative assessment of ageing status, retrospective design.

Strength: Good sample size.

1

Limitations: Dated, no qualitative assessment of ageing status, retrospective design.

Strength: prospective design.

Marmiroli et al. Brazil, 2008-2010

Pichon et al.

Elshal et al.

Piao et al.

France, 2013-2016

Canada, 1998-2012

Korea, 2009-2013

100

60

264

38/579

> 75

> 75

> 80

> 80

79

84

84

86

TURP, Open prostatectomy

20

Mixed (TURP, PVP, HoLEP)

22

Laser Surgery (HoLEP, PVP)

HoLEP

19.6

13.2

1.70

0

0

EUT Congress News

Limitations: small sample size, different procedures (TURP, PVP, HoLEP) evaluated together in the study.

Strength: Good sample size, standardized collection of complication with Clavien-Dindo Classification.

Limitations: retrospective design, long study interval, no qualitative assessment of ageing status.

Strength: Prospective design, standardized collection of complication with Clavien-Dindo Classification.

Limitations: Small sample size, no qualitative assessment of ageing status.

general population of Reich study. Wyatt et al., in 1989 first assessed TURP outcomes in octogenarians, showed a significantly higher morbidity and mortality rate, 71% and 5% respectively. A decade later, in 1996, Matani et al. reported, in octogenarians undergoing TURP, a morbidity rate of 26% and a mortality rate of 1.2%, respectively. In most recent series exploring the same topic, a downward trend regarding complications (about 20%) and mortality (0-1%) has been found (Table 1); however morbidity remains persistently higher than in the general population of Reich study.

Nevertheless, except in the Pichon series, none of the above studies performed a qualitative analysis of the ageing status. They focused only on age and had not made any distinction between patients with harmonious aging and patients with pathologic aging.

While Pichon et al. classified their elderly population, according the brief geriatric assessment (BGA) and the comprehensive geriatric assessment (CGA), into three groups: ‘‘vigorous’’, ‘‘vulnerable’’, and ‘‘sick’’. The mean morbidity rate in this study was in line with the other studies (22%) in ageing population, but it was significantly higher for the ‘‘vulnerable” and “sick’’ groups (44%) compared with the ‘‘vigorous’’ group (15%) (p < 0.05). In this selected category the complications was almost comparable with the general population of the Reich study. In addition BGA can predict a poor result of surgery, ‘‘vulnerable” and “sick’’ patients had a higher risk to keep their indwelling catheter after the surgery compared with ‘‘vigorous’’ patients. In line with Pichon study, Tai et al. found that poor cognitive and functional statuses are independent predictors for an increased risk of postoperative delirium in the elderly patients undergoing TURP. Lower complication risks In synthesis, the collected evidences suggest that TURP is burdened by a two-fold complication rate in ageing patients when compared with general population undergoing the same procedure. However this unfavourable clinical scenario is evolving over time. As suggested by the downward trend in morbidity and mortality in most recent studies, we may speculate that advancement in surgical techniques and devices has probably lowered the risks of complications associated with TURP in older frail population. Moreover, we should keep in mind that there is a wide heterogeneity within the geriatric patients, with a considerable variability of life expectancy and health status within the same age group.

of the population and to adopt a therapeutic strategy adapted to the level of vulnerability.

Consequently, we should seek alternative therapeutic strategies to TURP in particular in the most vulnerable portion of the elderly population. In recent years, several randomized clinical trials (RCTs) compared different laser techniques versus TURP and open prostatectomy, showing lower morbidity of laser procedures and at least equivalent functional outcomes.

The advantages of laser prostate surgery included in particular a superior haemostatic ability in anticoagulated patients, reduced blood losses and consequently a diminished blood transfusion rate.

However, the vast majority of patients enrolled in these RCTs generally approximately 65 to 75 years old. A very limited number of studies directly addressed the efficacy and safety profile of laser procedures in over 75 years old patients.

Elshal et al. performed a retrospective analysis of their patients who underwent laser prostate surgery between 1998 and 2012. They identified 264 octogenarians, 16.5% of the enrolled population. For this category the mean age at time of procedure was 84±3.5 years. Holmium laser enucleation of the prostate was performed in 171 (64.7%), holmium laser ablation of the prostate in 16 (6%), holmium laser transurethral incision of the prostate in 13 (5%) and photoselective vaporization of the prostate in 64 (24.3%). Procedures for octogenarians almost doubled in a decade, passing from 11% at the end of 2002 to 19% at 2012. Likewise, the most recent studies about the safety of TURP in elderly, about 20% of perioperative complications has been recorded even for laser surgery.

However, the vast majority (82.3%) was low-grade complications (Clavien grade I-II); high-grade complications (Clavien grade ≥ III) were only 17.7% of the total and no perioperative deaths occurred in the study. A longer operating time was an independent risk factor for perioperative morbidity in octogenarians, while functional outcomes were good and comparable with younger patients.

Similarly, Piao et al. evaluated prospectively the effect of age on the efficacy and safety of HoLEP.

In this study, patients ≥80 years had significantly higher rate of of hypertension, higher values of ASA scores, total prostate volumes, higher rates of urinary retention, and use of anticoagulants at baseline.

Therefore, the quantitative assessment of age should Moreover, the mean operative time and enucleation not be the only predictive factor to define a therapeutic weight were higher in octogenarians when compared strategy in the elderly. As yet proposed by the European with younger patients. In addition, elderly men had a Urology Association (EAU) in agreement with the Society longer hospital stay time (2.9±1.8 days) than general of Geriatric Oncology (SGO) for the management of population (2.3±0.7 days; p = 0.001). Nevertheless the In Table 1 we summarized the outcomes, morbidity and prostate cancer, a standardised geriatric assessment that morbidity rate assessed by Clavien-Dindo classification mortality rate from TURP in studies that directly takes into account the multidimensional aspect of aging (about 13%) and the functional outcomes were addressed the frail elderly population, comparing to the would make possible to better identify the heterogeneity comparable regardless of age.

18

Limitations: No qualitative assessment of ageing status, no inclusion of frail patients.

Strength: Qualitative assessment of ageing status, prospective design.

From these preliminary evidences laser surgery seem to be an effective and safe option for elderly patients lowering morbidity, in particular the high-grade complications. However, no qualitative assessment of ageing status in the abovementioned studies has been performed, therefore no definitive recommendations can be drawn in particular in the frailest segment of the elderly population.

In this subgroup of patients, Prostatic Urethral Lift e PAE may be more attractive options. In fact as extrapolated from RCTs and real-life studies in general population, these therapeutic alternatives may be performed in almost all cases under local anaesthesia as a day case with a very low rate of low-grade complications. The most common adverse events experienced in the studies were dysuria, haematuria, and pelvic pain. These adverse events were mostly short-lived, typically resolving within two weeks without further sequelae. Nevertheless to our knowledge no studies have specifically assessed the safety of these surgical procedures in frail elderly patients.

Standardised geriatric assessment In conclusion, the available evidences suggest that octogenarians undergoing BPE surgery have acceptable perioperative morbidity regardless of the selected surgical procedure. However, ageing men are a heterogeneous cluster of population and a standardised geriatric assessment should be the key instrument to better stratify patients according to their surgical risk. Data extrapolated from RCTs in general population suggest that minimally invasive treatment should be preferred in (very) frail elderly patients; however, no conclusive recommendations can be draw without specific study on this topic.

References 1. Presicce F, De Nunzio C, Tubaro A. Can Long-term LUTS/ BPH Pharmacological Treatment Alter the Outcomes of Surgical Intervention? Curr Urol Rep. 2017 Sep;18(9):72.

2. Pichon T, Lebdai S, Launay CP, Collet N, Chautard D, Cerruti A, et al. Geriatric Assessment Can Predict Outcomes of Endoscopic Surgery for Benign Prostatic Hyperplasia in Elderly Patients. J Endourol. 2017 Nov;31(11):1195-1202.

3. Elshal AM, Elmansy HM, Elhilali MM. Transurethral laser surgery for benign prostate hyperplasia in octogenarians: safety and outcomes. Urology. 2013 Mar;81(3):634-9.

4. Piao S, Choo MS, Kim M, Jeon HJ, Oh SJ. Holmium Laser Enucleation of the Prostate is Safe for Patients Above 80 Years: A Prospective Study. Int Neurourol J. 2016 Jun;20(2):143-50.

Saturday, 17 March 10.15-14.00: Meeting of the EAU Section of Female and Functional Urology (ESFFU); Management of complex cases in male and female functional urology

Saturday, 17 March 2018

My journey in prosthetic urology Teaching is the most difficult task in surgery but is also the mark of an expert Dr. Ignacio Moncada Dept. of Urology Hospital Sanitas La Zarzuela Madrid (ES)

They say that nothing happens by chance, everything has a purpose and you only know that purpose when you are far along the journey. When you connect all the dots, then the picture appears.

My journey Mine is the fourth generation of doctors, I was born with Medicine in my blood. When I was a medical student, in 1980, I spent three months in US with a friend of my father who was a urologist.

I never thought that urology could be my specialty but it turned out to be my passion too. In those days, I witnessed for the first time in my life a penile implant. The patient was a diabetic with a very large penis and I was astonished with the procedure.

So, I said to myself, I want to do this surgery. When I finished medical school, I started training as a resident doctor in one of the best hospitals in Madrid (Gregorio Marañón) where I spent five years completing a fantastic urology residency. When I was a fourth-year resident I spent a few months in Boston with Bob Krane’s group learning about Sexual Medicine and penile surgery. Irwin Goldstein and Iñigo Saenz de Tejada were the big names there and I kept up my connection with them for many years.

They were the pioneers of Sexual Medicine and I was lucky to be close to them at that time and for many years afterwards. Iñigo moved to Madrid and although he was not a surgeon he became my mentor and my close friend until his premature death.

When I finished my residency in urology, I took a position as urologist in Gregorio Marañón Hospital and I was very fortunate to have a Head of Department, Carlos Hernandez, who wanted to give doctors responsibility very soon. He put me in charge of andrology at a young age. However, I liked surgery more than research, so I got involved in penile implant surgery and Peyronie’s disease surgery and started to publish, to participate in and to organize courses and seminars. As we were based in a University Hospital with residents and visiting doctors, we soon created a “school” with a style of implant that is still used today. We learnt from all the big names in Prosthetic Urology in the world such as Steve Wilson, John Mulcahy, David Ralph or Mariano Rossello just to name a few. But as much as with the masters, I also learned a lot from the young people who were once residents and then became masters themselves- Juan I. Martinez-Salamanca, Enrique Lledo, Javier Romero or Agustin Fraile just to mention a few.

Penile prosthetic implantation Nowadays penile prosthetic implantation surgery has an important role in the management of organic end-stage erectile dysfunction. The European Guidelines on Erectile Dysfunction recommend the implantation of a penile prosthesis.

The evidence of high efficacy, safety and satisfaction rates of both patients and partners is robust. Nevertheless, outcomes are not always perfect, complications arise and malfunctions are somewhat frequent.

method for penile prosthesis complications is the standard practice. This was my first “important” paper, published in Journal of Urology and some of the pictures in the paper were used by others to illustrate their presentations. (Figure 1)

you never introduce improvements. On the contrary, you need to analyze your results, particularly when something goes wrong and make the changes and innovation needed to do it better (improving your results).

Use of a penile extender ...2 Twenty years ago infections were much more common, and removal of the prosthesis was the standard of care of those cases. The consequence was a fibrotic shortened penis, very difficult to re-implant. We published for the first time the efficacy of a penile stretcher in facilitating re-implantation surgery. Now the use of a penile extender is common practice for all patients with any kind of penile fibrosis before surgery. This article prompted the medical use of a penile extender, now a recommendation in the EAU Guidelines for the conservative treatment of Peyronie’s disease.

And last but not least, my final reflection is, in my opinion, the most important of all: to teach others what you have learned. Teaching is the most difficult task in surgery; you start by assisting an expert, next step is to be assisted by an expert, then would come being assisted by someone less experienced than you and finally the most difficult is to assist someone less expert than you, making you the expert.

Dual implant in patients ...3 The popularity of radical prostatectomy as a treatment for prostate cancer led to an increasing number of patients with severe ED and stress urinary incontinence. The usual treatment is first to correct the incontinence and then proceed with the penile implant in those patients still willing to undergo further surgery. The alternative would be to perform this double implant at the same time through the same incision. We depicted in this paper our technique of doing this procedure pioneered by S. Wilson. Now, the double implant is also recommended as an option in the EAU Guidelines in such patients.

Inflatable Penile Prosthesis Implantation Without Corporeal Dilation…4 Typically, the implant involves the dilatation of the cavernosal bodies to make enough space to insert the cylinders. We demonstrated that this is not necessary in the virgin case, so you can avoid it with all the benefits of being less invasive: it saves surgical time decreasing complications, preserves complimentary erection and avoids retraction of the penis helping to maintain the penile length after implantation. Many implanters in the world are using this technique now.

Abdominoplasty and scrotal z-plasty…5 This paper on penile prosthesis in obese patients with hidden penis opened a discussion about the importance of the cosmetic aspect in penile surgery including Peyronie’s disease, as well as the role of lengthening procedures in patients with a short penis.

These papers were innovative in the field and reflected both the insight and the experience of surgeons interested in the search for better outcomes for our patients. It is also true that innovation is wholly linked to constancy and permanence in any medical field. Receiving recognitions like the Nikolay Alekseevic Bogoraz Medal awarded by the Russian Association of Andrology in 2010, or the Brantely-Scott Award of Excellence presented during AUA 2015 reflect the appreciation of my peers. In the end however, the most important acknowledgment comes from our patients.

Having come this far, I feel I am still learning every day. Sharing my experience with my colleagues and urologists in training is very professionally satisfying, long may it last.

How to become an expert The second part of this article is “How to become an expert”; it sounds a little pretentious for me to pretend to know how to become an expert as it assumes I am one. But in any case, as this is the title I have been given for this presentation at the EAU, I will outline my own experience. Probably this reflection can be applied to any discipline in life, it Mastering the surgical techniques for the implantation could be called “how to become an expert in anything”. But for sure in my case it all comes from of virgin cases but particularly when complications my experience as a surgeon. arise is a must for the modern urologist. Our experience, with around 1,000 penile prosthesis The first thing I believe to be fundamental is to get implanted in the last 25 years, has allowed us to help: find a mentor who can help you develop that explore different aspects of prosthetic surgery and to make innovations that improve the surgical outcomes. image in your head of the best way to do something.

Mentors act like a role model, giving you something I want to take you with me on my journey in Prosthetic Urology which can be better done from the to emulate and to aspire to. I have had several mentors in my life, but if I had to name only one that standpoint of some landmark papers, breakthrough would be Iñigo Saenz de Tejada, he always supported papers, that led to a change in penile prosthetic surgery and prompted some other publications. These and inspired me. To have a good mentor is not easy, maybe is just a matter of luck, but it can make all the are examples of these papers: difference in your professional career.

Buckling of cylinders may cause ....1 This paper was the first to demonstrate the role of MRI in penile The second thing I consider having utmost importance prosthesis to assess the correct position and right is the commitment factor. Ask yourself: How long am I function. Since then the use of MRI as a diagnostic going to be doing this? Doing something for a long Saturday, 17 March 2018

Figure 1: This photo was part of the author’s first key publication on penile prosthesis complications

time probably correlates with being decently good at it but committing in advance for the long haul changes it completely. Commonly we have colleagues who are interested in everything: oncology, lithiasis, incontinence, andrology but they do not focus on anything specific and try different areas. It is very hard to become an expert in anything if you don’t focus on one specific area with the intention of developing that chosen area.

Study and practice are the basis of the learning process in surgery: understand what to do and do it repeatedly. In penile prosthetic surgery you cannot fail, if there is an infection it won’t heal by itself, it will probably need removal of the device and this will be a disaster. So you need to program your steps, carry them out in a systematic way with no hesitation and no time for doubts, be quick and clean. If you change your technique continuously it always will be a new one for you and everyone in the OR (and that’s not good!).

Analyze your results and get feedback from patients.

Being systematic in your surgery does not mean that

In surgery, you are at the top when you are mentoring other surgeons. If someone considers you his mentor, his master in surgery, when he/she has a doubt of what to do in a difficult case and calls you for an opinion, that is when you can finally consider yourself an expert.

References 1. Buckling of cylinders may cause prolonged penile pain after prosthesis implantation: a case control study using magnetic resonance imaging of the penis. J Urol, 160; 67-71, 1998.

2. Use of a penile extender to facilitate penile prosthesis re-implantation after removal for infection. J Urol, 165, 1048, 2001.

3. Dual implant in patients with incontinence and erectile dysfunction. J Sex Med; 3(2):367-70, 2006.

4. Inflatable Penile Prosthesis Implantation Without Corporeal Dilation: A Cavernous Tissue Sparing Technique J Urol 183, 1123-1126, 2010.

5. Abdominoplasty and scrotal z-plasty associated to penile prosthesis implantation in patients with buried penis J Sex Med, Vol. 7, 403–464, 2010.

Saturday 17 March 10.15-15.30: Meeting of the EAU Section of GenitoUrinary Reconstructive Surgeons (ESGURS), Updates in genito-urinary reconstruction

ENUCLEATION OF THE PROSTATE using Hemera Pulsed Thulium laser with updated settings

Dr J.B Roche

Groupe Urologie Saint- Augustin - Bordeaux (Fr) In this video, we will present a laser prostate enucleation using updated settings, along with a modified en bloc dissection. At last year’s ESUT session, we showed an original approach to enucleation using a pulsed Thulium laser.

For better performance, we changed settings to achieve a better bubble effect, thus achieving a clearer enucleation plane.

We will show how the thulium laser used in a pulsed mode can be combined with a minimally invasive endoscopic technique to treat large prostatic adenomas.

Pre-recorded video

March, 17th 16:54

eUro Auditorium (Level 0)

Procedure performed with 200 W Hemera ® Thulium Rocamed Laser

EUT Congress News

19

Oncological outcomes following robotic-assisted RC Tumour recurrence after RARC linked to biology, not to surgical procedure A multi-centre RARC series published by the EAU Scientific Working Group (ESWG) identified that early recurrences at any site occured in 4.1% of Despite the apparent advantages of RARC, debate patients at three months, 19.8% remains as to whether minimally invasive surgery negatively impacts survival outcomes, potentially due at 12 months and 25.4% at 24 months20, which is equivalent to to inadequate resection, suboptimal lymph node dissection or alteration of recurrence patterns due to early recurrence rates seen in ‘tumour seeding’ related to the pneumoperitoneum ORC series18,21-23. The ESWG or insufflation12-14. A recent multicenter study reporting series identified that distant early recurrences in laparoscopic radical cystectomy recurrences in the bones, lungs New cases of bladder cancer are diagnosed in (LRC) found 8.7% of patients with favorable and liver were most frequent approximately 110,500 men and 70,000 women each pathological characteristics (pT2 N0 R0 or less) and that pelvic lymph nodes year1. In 2018, it is predicted to be the fourth and developed disease progression in the first 24 months were the commonest site of twelfth most common malignancy in males and post-operatively, concluding that the local recurrence. This is also pneumoperitoneum may have contributed to these females, respectively in the United States2. 38,200 consistent with the pattern of patients in the European Union and 17,000 US patients relapses15. recurrences seen in previous die from urothelial bladder cancer each year1. studies of ORC and in autopsy Figure 1a: K-M estimates of recurrence free survival series21,24. Regarding ‘unusual ORC vs RARC Mortality rates have remained relatively stable in recurrence patterns’14,17, they Another single-centre publication compared open recent years2. At presentation approximately 20-30% identified five patients (0.7%) radical cystectomy (ORC) with RARC, reporting a of bladder cancers are muscle-invasive and would with peritoneal carcinomatosis higher incidence of peritoneal carcinomatosis and and two patients (0.3%) with likely be fatal for patients within two years if left extraperitoneal lymph node recurrences in patients untreated. Radical cystectomy and extended pelvic undergoing RARC and concluding that the distribution port site (wound site) metastasis, which are both of lymphadenopathy provide the best chance for of distant recurrences differed between the two low incidence and consistent long-term survival and are considered the standard of approaches14. The potential for ‘differences’ in care for clinically localized muscle-invasive bladder recurrence patterns was again recently noted by Dr. with published open series25. cancer and high-grade recurrent non muscle invasive Marzouk and colleagues from Memorial Sloan disease3.

Kettering Center, when they reported oncological Whilst debate remains on the potential for detrimental effects outcome updates from their randomized control trial The incidence of bladder cancer increases with comparing open (ORC) to RARC16. Between 2010 and from RARC on early recurrence advancing age. Considering the increasing life 2013, 118 patients with clinical stage Ta-T3 bladder patterns, there is little evidence expectancy and the increasing proportion of elderly cancer were randomized to RARC (n=60) or ORC of an overall higher incidence of people in the general population, radical cystectomy (n=58). In this latest update the median follow-up for early recurrences following will be considered for a growing number of elderly RARC. Early RFS rates correlate these patients was 4.9 years (IQR 3.9, 5.9)17. They identified 44 patients with recurrences: 25 after ORC, patients. However, radical cystectomy by any closely with five-year RFS and approach is complex surgery associated with and 19 after RARC. There were 14 abdominal overall survival18 and current recurrences in five RARC patients, and four significant peri-operative morbidity in a susceptible evidence from cumulative patient cohort who are frequently elderly with recurrences in two patients following ORC. Figure 1b: K-M estimate comparing RFS between patients with non-favorable (pT>2 or analysis indicates satisfactory associated co-morbidities. The risks of surgery N+ or R+) and favorable pathological characteristics (pT≤2 N0 R0) medium and long-term RFS therefore need to be balanced with the benefits of Concluding that although the RCT revealed no rates and cancer specific treatment4,5. significant difference in disease recurrence rates or survival19,22. In a recent review cancer-specific survival between RARC and ORC, they RFS rates at two years post-operatively ranged from associated with extensive metastases at multiple had observed patterns of recurrence based on Potential advantages of robotic –assisted radical sites24. In RARC series the incidence of peritoneal 67-81% in RARC series22. Even papers highlighting cystectomy (RARC) include reduced complications6, surgical technique, which were of interest. Stating unusual recurrence patterns as a possible indicator of carcinomatosis has been found to be low at 3.5%, less intra-operative blood loss due to the prolonged that the study was not powered to establish detrimental effect have not shown an increased even with long-term follow-up19. pneumoperitoneum, quicker return of bowel function, differences in patterns of recurrence17. incidence of recurrences compared to the ORC, in fact shorter hospital stay and earlier return to normal in both these series the overall incidence of recurrence Review of patients in the ESWG series with peritoneal activities, which would all theoretically allow more was lower in the RARC group14,17. carcinomatosis and port-site metastasis revealed all It is recognised that early recurrences are a poor immediate administration of adjuvant chemotherapy patients to have high-grade urethelial cancer20. Four prognostic indicator, which correlates closely with when required7. RARC has been shown to be of the five patients with peritoneal carcinomatosis Recurrence patterns five-year RFS and overall survival18. However, the advantageous in elderly patients and other current evidence for long-term outcomes following Previously hypothesised potential negative effects of presented with multiple metastases and 80% had upstaging of disease, from organ-confined to susceptible groups8. The combination of RARC with an RARC shows acceptable oncological outcomes RARC, such as insufflation, the pneumoperitoneum enhanced recovery program has been shown to comparable to open series19. A multi-centre study and methods of specimen extraction remain non-organ confined disease and only one (20%) further reduce the recovery time after cystectomy9,10. unproven. Recurrence patterns attributed to the received NAC. These findings further indicate that analyzing 702 RARC patients with a minimum of five peritoneal carcinomatosis from tumour seeding is pneumoperitoneum and insufflation include years follow-up (median 67 months) reported a related to tumour biology rather than the The number of RARC’s performed in the United States five-year recurrence- free survival (RFS) of 67%. peritoneal carcinomatosis and port site metastasis14. pneumopertineum or other ‘effects’ of a RARC is steadily increasing, however, <20% of radical Factors associated with any recurrence were positive Peritoneal carcinomatosis incidence has been found cystectomies are currently performed robotically11. lymph nodes, non-organ confined disease, and approach. Hypothesising that tumour biology is the to be as high as 19% in bladder cancer patients at main causative factor for early recurrence is also Indications are that RARC is gradually being adopted positive surgical margin rates (all p<0.001)19. autopsy, but importantly it is most frequently consistent with the laparoscopic cystectomy series that described unusual early disease recurrence patterns among patients with favorable disease characteristics (pT≤2N0R0)13. This series reported 8.7% of patients with pT≤2N0R0 developed recurrences within 24 months, with most of these patients showing progression to high-volume disseminated metastatic disease. Multi-variate logistic regression analysis identified pT stage as the only factor significantly associated with early recurrence in this multi-centre study13.

Dr. Justin W. Collins Dept. of Urology Karolinska University Hospital Stockholm (SE)

and that the technique is evolving, with an increasing number of centres performing totally intracorporeal RARC6.

The ESWG series20 reported similar early recurrence rates (See Figure 1). But when you consider that approximately 80% of recurrences occur in the first two years [18,26], recurrence rates of 8.7% in pT≤2N0R0 in the first two years, equates to the five-year RFS of 89% in pT2N0 patients previously reported in a ‘Gold Standard’ ORC series21. Indeed, early recurrences with ‘favorable disease’ can be expected in a proportion of patients, pT2N0 has been shown to be a heterogeneous group with approximately a third being stratified as high-risk, showing oncological outcomes similar to pT3N0 disease27.

Accepted early indicators of oncological efficacy include PSM rates and lymph node yields3. Several cumulative analyses of RARC series have shown respectable PSM rates and median extended pelvic lymph node yields consistent with open series and RARC series11,19-22. PSM rates were strongly associated with pathological staging19-21.

Figure 1: Unpublished K-M estimates from the ESWG multi-institutional database focusing on the centres performing totally intracorporeal RARC

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Other factors consistently associated with early recurrence are lymph node involvement, advanced pathological stage and positive surgical margin Saturday, 17 March 2018

compared to organ confined disease, was also a significant risk factor for early recurrence (HR=3.8 p<0.0001), as was a PSM (HR 4.5 p<0.0001)20.

Female gender was also seen to be a risk factor (HR 1.63 p<0.05) and has previously been identified as an independent adverse prognostic factor for both recurrence and progression of bladder cancer28.

Survival benefits Whilst reported early and late outcome measures of oncological efficacy will rightly dictate future adoption rates of RARC, current evidence indicates survival benefits of radical cystectomy in elderly or co-morbid patients previously considered unsuitable for major surgery29. The need for oncological efficacy therefore needs to be increasingly balanced with the risks of surgery. It is recognized that an RARC approach is advantageous in elderly patients and other susceptible patient groups7 and there is evidence of changing patient demographics in RARC series10.

The potential additional advantages of a totally Figure 2a: K-M estimates of recurrence free survival depending on pathological T stage intracorporeal RARC technique, include less morbidity from the operation, reduced transfusion rates19. In the ESWG cohort20, we see early recurrences rates and enhanced recovery8,10. Quicker recovery associated with these variables on the Kaplan Meier following surgery should also result in improved estimates (See Figure 1), giving further evidence that opportunities for earlier administration of adjuvant early recurrences following RARC are primarily chemotherapy, when pathological results or early related to tumour biology and not the modality of recurrences indicate the need8. surgical treatment. On regressional analysis of the ESWG series, the risk of recurrence was associated Although the selection biases of patients for optimum management outside of prospective randomized with positive compared to negative lymph nodes (N1 vs N0 HR= 3.6 p<0.0001 and N2 vs N0 HR=5.6 controlled trials can limit direct comparison with alternative treatments, it is also evident that due to p<0.0001). Pathological non-organ confined, when

the heterogeneity of aggressive urothelial cancer, it is difficult to accurately identify the best prognosis patients prior to surgery. To enable true comparison between treatments, robust molecular or biological markers associated with accelerated disease progression are required, but they are currently lacking in the clinical setting. This inability to accurately predict metastatic risk pre-operatively is a possible explanation for why smaller study numbers have concluded differences in early recurrence patterns between RARC and ORC14.

Oncological efficacy Indicators of oncological efficacy following RARC, namely PSM rates and PLND yields are comparable to ORC series. Whilst several groups have indicated potential for unusual recurrence patterns after RARC, their findings do not correlate with either an increase in recurrence rates or decrease in cancer specific survival. Current evidence indicates that early recurrence rates and RFS rates following RARC appear equivalent to published ORC series.

Figure 2b: K-M estimates of recurrence free survival depending on pathological

In all series, positive lymph Node stage nodes, non-organ confined disease and PSMâ&#x20AC;&#x2122;s were associated with poor oncological outcomes, indicating tumour recurrence following RARC are primarily related to tumour biology and not the modality of surgical treatment.

Editorial Note: Due to space constraints, the reference list can be made available to interested readers upon request by sending an email to: communications@uroweb.org

Friday 16 March 12.30-15.45: Urology Beyond Europe, Joint Session of the European Association of Urology (EAU) and the Korean Urological Association (KUA)

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Antibiotic treatment’s collateral effects Antimicrobial stewardship, critical antibiotic use are crucial to minimise bacterial infections Dr. José Medina-Polo Department of Urology Hospital Universitario 12 de Octubre Madrid (ES)

A primary concern for worldwide healthcare systems is the increasing incidence of antibiotic resistance in healthcare-associated infections (HAIs) and also in the outpatient setting. Moreover, the emergence of multidrug-resistant organisms (MDRO) is a worrisome point as the selection of an appropriate antibiotic treatment is a challenging task.

Several definitions for MDRO have been proposed such as those microorganisms with resistances to three or more antibiotic classes. It is recommended to follow the definition by the Centers for Disease Control and Prevention, which considers MRDO as microorganisms, predominantly bacteria, that are resistant to one or more classes of antimicrobial agents. Certain types of microorganisms deserve special attention such as extended-spectrum beta-lactamase (ESBL) producing Enterobacteriaceae or those resistant to carbapenems, Enterococcus resistant to vancomycin, and Methicillin-resistant Staphylococcus aureus (MRSA).

Antibiotic selection A correct selection of antibiotics is of paramount importance. Some drugs not frequently prescribed in this setting, such as fosfomycin and nitrofurantoin, are usually associated with a lower resistance rate, and they are considered an attractive alternative in the management of urinary tract infections with the isolation of ESBLproducing bacteria and MDR microorganisms.

Fosfomycin shows good activity against common uropathogens including ESBL-Enterobacteriaceae.

Parenteral administration of fosfomycin can be effective whether urinary tract infections are caused by ESBL Enterobacter, Pseudomonas aeruginosa, and vancomycin-resistantEnterococcus. However, fosfomycin is not recommended for pyelonephritis as low concentrations in serum and renal tissues are achieved. Nitrofurantoin also offers good efficacy against Enterobacteriaceae such as E.coli, Klebsiella, and Enterobacter. However, it is not effective against Proteus and Pseudomonas.

microorganisms. Moreover, a proper indication regarding prophylaxis is required (indication and no indication, duration, type of antibiotic). When the infection is diagnosed, the selection of antibiotics may be challenging as anywhere from 15% to 45% of infections due to ESBL-producing bacteria are not appropriately managed. On the one hand, an adequate empirical treatment must be chosen. On the other hand, broad-spectrum antibiotics should be avoided. Moreover, antibiotics must be selected while taking into account the appropriate dosage, an adequate route of administration, and administration timing. Before selecting an antibiotic treatment, previous cultures must be reviewed as high resistance rates are reported after previous antibiotic therapies.

Another critical point is asymptomatic bacteriuria, which does not require treatment except in pregnant women or previous to urological instrumentation. Therefore, patients with urinary catheters, pyuria or malodorous urine without fever or chills should not be treated with antibiotics.

For severe infections caused by MDRO including methicillin-resistant Staphylococcus aureus (MRSA), Acinetobacter baumanni, P. aeruginosa and carbapenemase-producing bacteria, antibiotics such as tigecycline and colistin are indicated. Collaboration with an infectious disease physician is advised for these patients.

Infectious complications Infections due to Clostridium difficile are another complication related to antibiotic treatment. It is the most common cause of infectious diarrhoea among hospitalised patients. This type of infection has risen sharply over the last decades. C. difficile may be found in faecal flora in up to 20-50% of hospitalised patients as asymptomatic colonisation or while producing an infection. The high incidence of C. difficile as an asymptomatic carrier both in community and hospital settings is related to chronic antibiotic use and with antibiotic resistance. The bacteria produce endotoxins, which confer the organism’s virulence with a cytotoxic action on the bowel mucosa that causes the infection with a clinical presentation range from uncomplicated diarrhoea to pseudomembranous colitis and colonic perforation.

Most of the patients with infection due to C. difficile have had previous antibiotic treatments with broad-spectrum antibiotics (cephalosporins, aminoglycosides, amoxicillin/clavulanic acid and fluoroquinolones).

Among urological patients, high rate of antibiotic resistance has been reported due to specific risk factors such as urinary catheters and surgery during hospitalisation. According to data from our In recent years antifungal resistance is also increased, department, there is a higher risk of MDRO isolation in particular in case of Candida glabrata and in a patient with immunosuppression [OR 2.57], Aspergillus fumigatus. Fungal infections are more urinary lithiasis [OR 2.309], a prior urinary infection common in patients with immunosuppression, those [OR 2.45], and an indwelling urinary catheter prior to with cancer and transplant recipients. MRDO may be admission [OR 1.79]. The highest rates of MDRO were considered as a collateral effect of antibiotic found among patients with HAIs and a double-J stent treatment. Another worrisome consequence related to and a nephrostomy tube. We have also analysed antibiotic treatment is Clostridium difficile infection. infections due to carbapenem-producing bacteria in Both the isolation of multidrug-resistant bacteria and patients hospitalised in our Urology ward, and each Clostridium difficile are associated with high of them had a urinary catheter, and two out of 12 had morbidity and mortality rates, longer hospitalisation immunosuppression. and higher costs. It is estimated that MRDO infections increase hospitalisation cost by 10-30%, and C.difficile A survey carried out in Germany reported that infections increase the hospitalisation stay by a mean urologists were more confident prescribing the correct of nine days. dosage and duration of antibiotics. However, both urologists and non-urologists had poor knowledge MDRO are commonly isolated in patients hospitalised about antibiotic stewardship. in a urology ward with hospital-acquired infections.

According to data from GPIU-study 2003-2013 (Global The main points for minimising resistance to Prevalence Study on Infections in Urology) carried out antibiotics, selecting appropriate empirical by the EAU Section of Infections in Urology (ESIU), antibiotic therapy, and optimising outcomes are an among patients hospitalised in a urology ward and adequate knowledge of risk factors as well as with healthcare-associated urinary tract infections, microbiological and resistance patterns for the 45% of Enterobacteria and 21% of P. aeruginosa were isolation of multiple-drug resistant multidrug-resistant. Moreover, the resistance rate for imipenem was 8% (Figure 1 summarise resistance rate from GPIU study). Higher resistance rates were reported in a case of urosepsis.

Furthermore, MDRO are isolated as a hospitalacquired or healthcare-associated infection. This term includes when patient was hospitalised within 90 days before the infection, or receives long-term healthcare, intravenous therapy, specialised wound care, or hemodialysis. ESBL-producing bacteria are also isolated in a community setting. Misuse and the indiscriminate use of broad-spectrum antibiotics are related to the growing frequency of microorganisms that are resistant to antibiotics.

Inappropriate use of antibiotic agents in human and food producing animals also contribute to the development of antibiotic resistance. In particular, there is a clear connection between the prescription of fluoroquinolones and the incidence of resistant strains.

Therefore, in areas with higher resistance to quinolones, they should be avoided as empirical treatment. Moreover, ESBL-producing Enterobacteriaceae are also frequently resistant to other antibiotics such as fluoroquinolones and aminoglycosides. Carbapenems are usually the antibiotics prescribed in the management of infections due to MDRO, especially those caused

by ESBL-producing bacteria. However, carbapenemase-producing bacteria are also emerging, and it is a worrisome problem as up to a 50% mortality rate has been described in patients with bloodstream infections with carbapenem-resistant Enterobacteriaceae.

Furthermore, few treatment options are available for carbapenem-producing bacteria.

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EUT Congress News

Other risk factors for C. difficile isolation are an admission from a nursing home, the existence of severe underlying diseases, and the use of anti-ulcer medications. Moreover, mechanical bowel preparation may increase the risk of C. difficile infection. It is estimated that the chance of a positive testing for C. difficile is 0.21%. In urological patients, C. difficile infections are more common after urologic procedures that require bowel use such as radical cystectomy. The incidence of C. difficile infections ranged from 2.2% to 11.7% after a radical cystectomy in comparison with 0.02% after a prostatectomy and 0.23% after a nephrectomy. When C. difficile infection

is suspected, the patient must be considered to be “highly infectious”, and the protocol for isolation must be started. Moreover, there is a high risk of environmental contamination in the room when a C. difficile infection occurs.

In 2013, The Centers for Disease Control and Prevention (CDC) classified the infection due to C. difficile in the highest “hazard level” for development of antibiotic resistance, on the same level as carbapenem-resistant Enterobacteriaceae.

Regarding the prevention of C. difficile, it should be borne in mind that spores are highly resistant to alcohol. Thus, alcoholic solutions for hand-washing may be not efficacious. C. difficile infection may also be presented as a recurrent disease, and it is associated with increased mortality. Antibiotic treatment in the case of C. difficile infections should be chosen according to clinical characteristics and severity and may include metronidazole, vancomycin, or fidaxomicin. Faecal transplantation can be required in patients with a severe and recurrent infection.

In summary, the following measures are recommended in order to minimise the emerging growth of multidrug-resistant organisms (MDRO): • Training regarding MDRO, local microbial prevalence, and resistance patterns, and prescription of antibiotics are required for healthcare providers; • Information about prevention of infections is not only necessary for healthcare personnel, it should also include everybody in contact with the patients and relatives who visit them; • The prescription of antibiotics should be adequately indicated and justifiable, avoiding broad-spectrum antibiotics; • Antibiotic prophylaxis according to the recommendation by Best Practice Guidelines (EAU and local microbiological and resistance rate).

Perioperative antibiotics should not routinely be maintained beyond the first 24 hours after surgery unless there is an infection; • Antibiotic choice should be determined according to a risk factor for MDRO; • Improve adherence to measures for infection prevention, including shortening, when possible, the duration of urinary catheterisation; • Methods for enhanced microbiological diagnosis with rapid detection of resistance are advisable; and • Antimicrobial Stewardship Programs dedicated to improving antibiotic are required and they have demonstrated a reduction in the incidence of infections and isolation of MDRO bacteria and C. difficile infections.

References 1. Cai T, De Nunzio C, Salonia A, Pea F, Mazzei T, Concia E, et al. Urological infections due to multidrug-resistant bacteria: what we need to know? Urologia 2016;83:21–6. doi:10.5301/uro.5000123.

2. Global Alliance for Infections in Surgery Working Group.

A Global Declaration on Appro-priate Use of Antimicrobial Agents across the Surgical Pathway.

Surgical Infections 2017;18:846–53. doi:10.1089/ sur.2017.219.

3. Heinlen JE, Salinas L, Cookson MS. Clostridium difficile Infection in Contemporary Uro-logic Practice. Urology 2018;111:23–7. doi:10.1016/j.urology.2017.06.035.

4. Lebentrau S, Gilfrich C, Vetterlein MW, Schumacher H, Spachmann PJ, Brookman-May SD, et al. Impact of the medical specialty on knowledge regarding multidrugresistant organisms and strategies toward antimicrobial stewardship. Int Urol Nephrol 2017;49:1311–8. doi:10.1007/ s11255-017-1603-1.

5. Medina-Polo J, Arrébola-Pajares A, Pérez-Cadavid S, Benítez-Sala R, Sopeña-Sutil R, Lara-Isla A, et al.

Extended-Spectrum Beta-Lactamase-Producing Bacteria in a Urology Ward: Epidemiology, Risk Factors and Antimicrobial Susceptibility Patterns. Urol Int 2015;95:288–92. doi:10.1159/000439441.

6. Tandogdu Z, Bartoletti R, Cai T, Çek M, Grabe M, Kulchavenya E, et al. Antimicrobial re-sistance in urosepsis: outcomes from the multinational, multicenter global prevalence of infections in urology (GPIU) study 2003-2013. World J Urol 2016;34:1193–200. doi:10.1007/ s00345-015-1722-1.

Saturday 17 March 10.00-14.40: Joint meeting of EAU Section of Andrological Urology (ESAU) and the EAU Section of Infections in Urology (ESIU) – When basic science meets clinical practice

Saturday, 17 March 2018

Office Urology: Meeting the challenges Prostate biopsy issues top agenda of ESUO

By Joel Vega The new EAU Section of Urologists in Office (ESUO) will focus on prostate biopsy issues during its ’first’ annual meeting, following its official launching last year in London. The topic is of prime concern to office urologists with recent and still evolving changes in prostate cancer detection such as new imaging techniques.

“We have headlined our meeting her in Copenhagen as “All about prostate biopsy in office,” as this reflects an important method in urologic office done in all countries,” said ESUO Chairman Prof. Dr. Helmut Haas (DE).

Haas said the session will be moderated by office urologists, with expert lectures by Profs. Maurice Stephan Michel (DE) and Jochen Walz (FR), and Drs. Stefan Czarniecki (PL) , Stefan Haensel (NL), and Robert Schneider (CH). Michel will discuss indications for biopsy, patient’s preparation and biopsy procedures. Walz, meanwhile, will examine TRUSand MRI-guided biopsies, going through patient selection, benefits, drawbacks and future prospects.

Management of biopsy complications will be discussed by Haensel, while Czarneicki will explore

the role of biomarkers in prostate cancer treatment.

Schneider will look into pioneering experiences and lessons from a fusion biopsy network in Switzerland.

“We aim to have an interactive session as much as possible, stimulating the audience to provide critical views and feedback back to the panel of speakers,” said Haas. Aside from Haas, chairing the session are three ESUO members including Dr. Horst Brenneis (DE), Dr. Stefan Haensel (NL) and Dr. Robert Schneider (CH) who will provide preliminary remarks and lead the case discussions.

Haas said that as a new office under the auspices of the EAU, the section is taking all efforts for it to achieve its aims.

“Aside from promoting the ESUO to other EAU section offices and affiliates, we have conducted several surveys not only to find out the basic issues that concern office urologists but also to expand our contacts. We appreciate every little effort from our partners, both current and potential, that will help us expand the network of office urology,” Haas said.

“To all office urologists, send us an e-mail (esuo@uroweb.org) with your expectations.”

Special route itinerary During the congress this week, the section has created a “route itinerary” that will track and identify various meetings or sessions that are relevant or of interest to office urologists.

“Our section has created an itinerary here in Copenhagen which flags and scores the congress’ sessions according to their importance for office urologists. This will help our members or other office urologists to easily identify which sessions can add as priority to their congress agenda,” he said.

Aside from collaboration, the ESUO also offers to share its expertise

Sharing its expertise He also mentioned that aside from collaboration with other offices, the ESUO is also ready to offer its own expertise.

ESUO Chair Prof. Helmut Haas (left) with former EAU Sec. General Per-Anders Abrahamsson at at last year’s launching meeting of the ESUO in London

“Our section offers collaboration, especially based on the fact that most of the new developments in diagnostics and non-surgical therapy have to be transferred to outpatients under outpatient conditions. This means either in outpatient departments or in urologic offices. Office urologists know best the medical and patient-related considerations and administrative rules under which this can be done successfully,” Haas explained.

Haas said ESUO has been invited by the Slovak Urological Society to participate in the Slovak meeting of office urologists in April, where he will not only present the ESUO’s goals and projects but also the challenges and developments in office urology issues.

Nevertheless, he emphasized that a lot needs to be done by the ESUO for it to adequately cover or address the issues faced by office urologists.

Meeting Tip! ESUO Session, All About Prostate Biopsy, Saturday 17 March 10.15-14.00 Prostate biopsy is a core procedure in urologic office. During the meeting all relevant aspects of prostate biopsy in an office setting will be presented by recognized specialists: indication, procedures, the management of complications, and modern imaging.

The session is chaired by office urologists who will focus on the outpatient situation.

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Introducing European Urology Oncology New journal to offer a multidisciplinary view of GU cancer treatment

By Loek Keizer

audience including also non-surgical communities.”

The EAU is gearing up to offer a new scientific journal besides the established titles of European Urology and European Urology Focus. We spoke to the Editor-inChief of European Urology Oncology, Prof. Alberto Briganti (IT) about the journal’s mission, its intended audience and place in the landscape of medical journal publications.

“This is a new journal, and the EAU’s first official journal that is fully devoted to the research of genitourinary (GU) cancers,” Briganti explained.

“The novel idea is to assemble an editorial team of specialists from different GU-related disciplines who will work together to create a multidisciplinary journal in which different aspects of GU cancers such as medical oncology, radiation therapy, urology, imaging, pathology, molecular pathology are all represented.”

The journal will feature a range of sections, encompassing original research and reviews, discussions and some Guideline reviews. Briganti: “In GU cancers, prostate, kidney and bladder cancer are of course most prevalent, but we will also feature testicular, penile and other rarer cancers. We will have new research coming in, and we are also commissioning reviews on several ‘hot’ topics. We actively commission systematic review, metaanalysis, as well as opinion papers, on topics in which there is interest.”

European Urology Oncology will be published online, every other month. EAU members will automatically get access to the new journal.

Briganti: “The first edition is Prof. Alberto Briganti coming up soon. We are currently working on the first batch of papers that was accepted.”

Editorial team Chosen as the EU Oncology’s editor partly due to his previous editing experience, Briganti previously served on the European Urology editorial board, and co-edited EU Focus, together with Mr. James Catto (GB). He also served as guest editor for various issues of other medical journals.

Serving as Associate Editors are medical oncologist Dr. Laurence Albiges ( FR), urologist Dr. Gianluca Giannarini (IT), Prof. Ashish Kamat (US) who is involved in Urologic Oncology & Cancer Research and radiation oncologist Prof. Paul Nguyen (US). Managing Editor Ms. Emma Redley is based in Sheffield (GB), where the editorial team of European Urology is also based.

In terms of target readers, European Urology Oncology is designed to serve every medical expert dealing with GU cancers and their research, including urologists, medical oncologists, radiation therapists, imaging specialists and general research scientists.

“We have a dream team of editors with different backgrounds from all over the world, who are also key opinion leaders in their respective fields,” Briganti said. “Together, we will endeavor to make this journal essential for those publishing in the field. Competition is very high and we believe that if we insist on quality and rigorous peer reviews, the journal will improve and reach high standards.”

“Naturally, our core audience is the urologist,” Briganti said. “Urologists are among the main actors in GU treatment and represent majority of our readers. But the scope of our journal goes beyond urology and this might attract attention from other disciplines. Our ultimate aim is to have a wide

Motivation The genesis of European Urology Oncology came from the wealth of GU research that is submitted to European Urology. Roughly 80% of these submissions are related to genitourinary cancers, with many of the submissions deserving of an audience. Briganti: “If you consider the

number of papers submitted to the main journal, the numbers of straight rejections or rejections after peer review, so many of these are rejected despite their quality. These papers may be given another chance for publication under the EAU’s banner.”

“Authors who might initially not have their research accepted by the editors of European Urology, but who produce good quality papers are then given a chance to be considered for EU Oncology. I believe there is a lot of research which cannot always be allocated (due to space constraints) to the main journal. This is common practice in the industry, and many journals have sister publications in this way.”

“Ultimately, our goal is to publish innovative and high-quality papers which are of course distributed and well-read among the GU community.

The journal’s high-quality evidence should ultimately translate into practice-changing data.”

Initially, EU Oncology will draw on submissions to European Urology. “Ultimately, we hope to receive more and more direct submissions, but as the journal is in its infancy, James Catto and I decide which article should go be considered for EU Oncology after rejection from European Urology,” he added.

Whether the emergence of a new, GU cancerfocused journal would affect the current balance of contents of European Urology is difficult to say.

“I don’t foresee such a change,” Briganti said. “GU cancer research is so wide, and there are so many developments in terms of clinical and translational research. There will always be sufficient material for both journals. The main journal will continue publishing high-quality material in the field of GU cancers.”

“There is no intention to have any competition now or in the future. Both journals will cover research in uro-oncology. Additionally, European Urology also covers benign diseases, which we will not cover. It has the highest impact factor as it is the most highly-cited, most-read, most-distributed journal in the field. We are a small journal compared to European Urology, and there will not be any competition between us.”

Briganti anticipates more of a divergence between the journals, but not in the short-term. “It takes time to set up a new journal and make it fly properly. In the future, as we begin to receive more direct submissions, we may end up featuring more and more articles within the area of pure medical oncology or translational research,” he said. “Ultimately, our goal is to publish innovative and high-quality papers which are of course distributed and well-read among the GU community. The journal’s high-quality evidence should ultimately translate into practice-changing data.”

Role of medical journals Translating the research published in medical journals into practice-changing data is exactly the goal of medical journals. “The literature that an EAU membership provides should be useful for any urologist. This way they can stay up to date and be aware of changes in practice or future directions of practice,” Briganti said. He noted that a journal’s ultimate aim is to help improve patient care by publishing and circulating high-quality research, and direct the reader’s attention to new and evidencebased medicine. “We contribute to increasing the adherence to good treatment by practicing urologists,” he said.

European Urology, and soon, European Urology Oncology are not only widely-cited journals, but are also discussed at meetings, eventually helping shape medical guidelines. Briganti: “The ability to improve and change guidelines is the best that any journal can do. It means you are influencing the rules for good clinical practice. This makes a journal great.”

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1. Data on file 2. Hamstra, DA et al. Sexual quality of life following prostate intensity modulated radiation therapy (IMRT) with a rectal/prostate spacer: Secondary analysis of a phase 3 trial. Practical Radiation Oncology, Volume 8, Issue 1, e7 - e15 3. Karsh, L et al. Absorbable Hydrogel Spacer Use in Prostate Radiotherapy: A Comprehensive Review of Phase 3 Clinical Trial Published Data. Urology, Published online: November 23, 2017 4. Hamstra, DA et al. Continued Benefit to Rectal Separation for Prostate Radiation Therapy: Final Results of a Phase III Trial. Int J Radiat Oncol Biol Phys. 2017 Apr 1;97(5):976-985. © Augmenix, Inc. All rights reserved. Augmenix, SpaceOAR and SpaceOAR logo are registered trademarks of Augmenix, Inc.

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Predicting resistance to BCG therapy Emerging therapies for non-muscle invasive bladder cancer Dr. Edmund Chiong President, Singapore Urological Association Director of Urologic Oncology & Research, Department of Urology National University Health System (NUHS) Singapore (SG)

receptor (VDR) in strong linkage disequilibrium, rs1544410 and rs731236 were correlated to recurrence risk in an Asian cohort of NMIBC patients (unpublished data). In the same cohort, polymorphisms in cytokine genes such as IL17A (rs2275913) and IL18R1 (rs3771171) were also found to associate with BCG immunotherapy response (unpublished data).

Additionally, studies have also begun to evaluate epigenetic changes, which can alter gene activity and expression outside of gene sequence changes, as For decades, Bacillus Calmette-Guerin (BCG) predictors of patient response to BCG. In one study immunotherapy has been the standard of care to using a cohort of BCG treated T1G3 bladder carcinoma prevent recurrence and progression of the disease patients, the methylation profile of a panel of tumor after tumour resection, in non-muscle invasive suppressor genes (TSG) were assessed and differential bladder cancer (NMIBC) patients. Despite the efficacy methylation patterns of several TGS between patients of this treatment, a significant fraction of patients will with recurrence or progression were found9. ultimately develop recurrence and progression.

Differences between populations Patients who fail BCG therapy can also incur higher The allele frequencies of SNPs between populations medical costs due to the need for multiple procedures of different geographical background and ethnicity and closer surveillance for cancer recurrence. should be taken into consideration when developing Furthermore, patients who develop disease SNPs as predictive markers of response to BCG progression often have a poorer chance of survival. therapy. Genetic association studies are usually performed in a homogenous cohort. Whether these Clinicopathological parameters such as tumour grade, genetic predictors can be applied globally requires stage, multiplicity, recurrence rate, the concomitant validation. For an example, a Southern European presence of carcinoma in situ (CIS), gender and age population study reported a panel of eight immune have been linked to the response to BCG. However, it molecule SNPs predictive of BCG immunotherapy should be noted that these risk factors are not unique outcome10. However, only two SNPs from the panel to BCG but are associated with unfavorable NMIBC (IL17A rs2275913 and IL18R1 rs3771171) correlated to outcomes as well. Therefore, molecular diagnostic BCG treatment response in an Asian population; as tools have also been investigated, and may have a allele distributions were different between the two role to anticipate BCG immunotherapy failure1. population. This was also observed in NRAMP1 SNP association studies and deviation between the Canadian and Asian reports may be due to allele Detection for chromosomal aberration using urinary fluorescent in situ hybridization (FISH) shows potential distribution differences of the SNPs analyzed11,8. as a predictive tool of BCG failure. During BCG therapy, patients with positive FISH results after induction Thus, a better strategy may be to evaluate gene therapy were shown to have higher cancer recurrence transcription or function rather than SNPs. However, risk (3-5 fold) and progression risk (5-13 fold)2. this is rather difficult to do as it requires the development of predictive assays that correlate with Some studies have also attempted to associate the gene’s functional response to BCG therapy. tumour antigen expression with BCG response.

Furthermore, the response to BCG is complex, as it is However, correlation of a single tumour biomarker likely that many genes and proteins are involved, and with BCG response is confounded by the inherent therefore assays evaluating single proteins may be of molecular diversity of bladder cancer and the complex limited value. Although the evaluation of the global immunological cascade induced by BCG. p53, response of patient immune cells to BCG prior to Retinoblastoma protein, Survivin, B-cell lymphoma 2, therapy, using array-based technologies monitoring E-cadherin, Ezrin and Ki-67 are examples of tumour the transcriptional response or protein response to biomarkers being investigated1.

BCG may be a better approach, these platforms are still quite expensive to run. The development of Patients innate immunity to mycobacterium, tested targeted arrays may reduce the cost in the future. using purified protein derivative on skin, and clinical symptoms such as fever have also been considered as Emerging therapies probable predictors, though reports have not been Newer therapies on the horizon include an adjuvanted consistent3,4. cancer vaccine (MAGE-A3), which was safely administered with standard BCG therapy in NMIBC BCG immunotherapy induces an immunologic patients, in a Phase 1 trial, and it is the first to show an response. Following BCG instillation, an increase in increase in local T cell response12. Other intravesical leukocytes in urine has been associated with better immunotherapies in Phase 2 and 3 trials, include the BCG response5. Immuno-histochemical analysis of combination of BCG and vaccines (intradermal HS-410 immune cells in tumour tissue have also been or PANVAC), genetically engineered BCG and modified correlated with response to therapy6. A panel of adenovirus as monotherapy13. cytokines (IL2, IL6, IL8, IL18, IL1ra, TRAIL, IFN-gamma, IL12p70 and TNF-alpha), detected in the urine, with a The identification of regulatory T cells and high predictive value for BCG response was also being immunosuppressive immune cells in tumour tissue validated7. Increased expression of antigen presenting has also led to the evaluation of immune checkpoint molecules, major histocompatibilty complex class I blockers (ICB) such as anti-PD-L1 and anti-PD-1. PD-L1 which is the Programmed cell death-1 receptor, is and II, and ICAM1, has also been linked to favorable therapy outcomes. However, BCG induced antitumor expressed on activated T cells and binds to its ligand immunity is multifaceted and many molecules are PD-L1. This ligand is expressed on normal cells and by linked with response to therapy. Constant monitoring binding PD-1 it limits the immune response. of these molecules during BCG treatment may be PD-L1 expression is found in some bladder tumour challenging. cells, especially the higher grade ones, thus the Genetic variants tumour cells are able to block immune activation and Genetic differences between BCG therapy responders escape removal by immune cells. PD-L1 expression is and non-responders is another area of research reported to increase after chemotherapy or interest. Studies have centered around genes involved immunotherapy, and thus it may be a good candidate in the mechanisms of action of BCG. Genetic variants for intervention. Another immune checkpoint blocker, CTLA-4 (Cytotoxic T lymphocyte associated protein 4), such as Single Nucleotide Polymorphisms (SNP) in immune response-associated genes have been also blocks T cell activation by competing with CD28 correlated to BCG response. For example, allelic for binding to B7 ligands (CD80/CD86). In normal variants in Human glutathione peroxidase 1 (hGPX1) immune processes, it serves to limit immune and Natural resistance-associated macrophage responses but in cancer it limits T cell activation. The protein 1 (NRAMP1) has been associated with bladder PD-1 and CTLA-4 pathways do not overlap. Systemic cancer recurrence after BCG immunotherapy8.

ICB therapy with atezolizumab and durvalumab NRAMP1 plays an essential role in host-mediated (anti–PD-L1 antibodies) and pembrolizumab macrophage defense against intracellular (anti–PD-1 antibodies) are being evaluated in ongoing phase 2 monotherapy studies. Both are associated mycobacterial infection. The NRAMP1 promoter with lower immune-related adverse events compared variant rs34448891 allele 3 was also found to be associated with higher progression risk (p=0.014) to systemic anti-CTLA4. Thus, anti-PD-L1 and (unpublished data). Vitamin D is known to be anti-PD-1 therapies may provide additional treatment options for BCG-unresponsive and relapsing NMIBC important in macrophage-mediated mycobacterium tuberculosis eradication. Two SNPs in the vitamin D patients.

Saturday, 17 March 2018

There are also phase 1 and 1/2 studies in progress, that combine BCG with either atezolizumab or pembrolizumab for the treatment of NMIBC13.

However, a cautionary point to note is that the use of ICBs should be limited to patients with tumours expressing these proteins. Molecular analysis of patient tumours and immune cells will determine the best therapy for patients.

References 1. Kamat AM, Li R, O’Donnel MA, et al. Predicting Response to Intravesical Bacillus Calmette-Guérin Immunotherapy: Are We There Yet? A Systematic Review. European Urology. DOI: 10.1016/j. eururo.2017.10.003 2. Kamat AM, Dickstein RJ, Messetti F, et al. Use of fluorescence in situ hybridization to predict response to bacillus Calmette-Guerin therapy for bladder cancer: results of a prospective trial. J Urol 2012;187:862–7 3. Bilen CY, Inci K, Erkan I, Ozen H. The predictive value of purified protein derivative results on complications and prognosis in patients with bladder cancer treated with bacillus Calmette-Guerin. J Urol 2003;169:1702–5 4. Sylvester RJ, van der Meijden AP, Oosterlinck W, et al. The side effects of Bacillus Calmette-Guerin in the treatment of Ta T1 bladder cancer do not predict its efficacy: results from a European Organisation for Research and Treatment of Cancer Genito-Urinary Group Phase III Trial.

Eur Urol 2003;44:423–8.

5. Jackson AM, Alexandroff AB, Kelly RW, et al. Changes in urinary cytokines and soluble intercellular adhesion molecule-1 (ICAM-1) in bladder cancer patients after bacillus Calmette-Guerin (BCG) immunotherapy. Clin Exp Immunol 1995; 99:369–75.

6. Renate Pichler, Josef Fritz, Claudia Zavadil, et al.

Tumor-infiltrating immune cell subpopulations influence the oncologic outcome after intravesical Bacillus Calmette-Guérin therapy in bladder cancer. Oncotarget 2016; 7(26):39916-39930.

7. Kamat AM, Briggman J, Urbauer DL, et al. Cytokine Panel for Response to Intravesical Therapy (CyPRIT): nomogram of changes in urinary cytokine levels predicts patient response to bacillus Calmette-Guerin. Eur Urol 2016; 69:197–200.

An apparatus (4–5 cm length, with 9 short needles) used for BCG vaccination in Japan, shown with ampules of BCG and saline (Photo: Y.Tambe/Wikipedia)

8. Chiong E, Kesavan A, Mahendran R, et al. NRAMP1 and hGPX1 gene polymorphism and response to bacillus Calmette-Guerin therapy for bladder cancer. Eur Urol 2011; 59:430–7.

9. Agundez M, Grau L, Palou J, et al. Evaluation of the methylation status of tumour suppressor genes for predicting bacillus Calmette-Guerin response in patients with T1G3 high-risk bladder tumours. Eur Urol 2011; 60: 131–40.

Editorial Note: Due to space constraints the reference list has been shortened. Interested readers can email at communications@uroweb.org to request for the full list.

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Robotic radical cystectomy Surgical hints, lymph node dissection and intracorporeal diversion Dr. Alejandro R. Rodriguez Chief, Urology and Urology Oncology Director, Robotics and Minimally Invasive Surgery Samaritan Medical Center New York (US) Radical cystectomy remains a procedure associated with high morbidity. A recent contemporary study that analyzed 6,510 patients over a six-year period (2010-2015), reported that 31.5% of patients experienced a complication and 40.7% of patients required a blood transfusion. The length of stay decreased over time from 10.6 days in 2010 to 9.2 days in 2015 (p<0.01), however readmissions increased slightly over the time period to 21.4% in 2015 (p<0.01)1.

The use of the robotic-assisted approach, for the surgical management of bladder cancer and reconstruction of a urinary diversion, has increased since its description in 20032. Contemporary studies on radical cystectomy series, report that 28.9% to 39.4% of patients underwent a robotic assisted approach3,4. Since more than five years ago, in our institution, as well as in others, 100% of the radical cystectomies and urinary diversions are performed using the robotic assisted technique5. Multiple studies, including randomized controlled trials, have demonstrated that Robotic assisted radical cystectomy (RARC) is comparable to open radical cystectomy (ORC) with regards to: surgical margins, number of lymph nodes resected, five-year cancer-specific and overall survival, as well as, local and distant recurrences6-12. Although, RARC may take longer (specially during the learning curve), it has demonstrated: less estimated blood loss, less risk of blood transfusions, and shorter length of stay6,13,14.

It is widely known that most postoperative complications following radical cystectomy arise from the urinary diversion reconstruction. Complications (30 and 90 day; Grade 3-5) have been comparable with both approaches (Open versus Robotic).

However, all the randomized control trials reported, have compared ORC to RARC with extracorporeal urinary diversion15.

Intracorporeal urinary diversion reconstruction may improve complications rates, and shorten even more the length of stay. Performing a diversion intracorporeally may influence gastrointestinal complication rates by reducing bowel manipulation, mobilization and exposure. A large retrospective series demonstrated that intracorporeal urinary diversions reduce gastrointestinal (23% to 10%; p<0.001) and infection related complications (18% to 10%; p=0.035); as well as, 30-day (15% to 5%; p<0.001), and 90-day readmission (19% to 12%; p= 0.016)16.

Since more than five years ago, in our institution, we perform a pure robotic-assisted radical cystectomy with intracorporeal urinary diversion (abdominal wall or orthotopic). There is a need for the new generation of robotic surgeons to familiarize themselves with anatomical landmarks, to prevent complications related to the approach of the pelvis, for the ablative oncological part of the procedure such as the extirpation of bladder cancer and lymph node dissection. Finally, diffusion of surgical hints for the creation of intracorporeal urinary diversions is necessary to prevent complications related to the fully intracorporeal reconstruction of the urinary tract.

Surgical technique Port placement starts with a 2 cm longitudinal incision, 5 cm above the umbilicus. Through this incision the peritoneal cavity is opened and a 12 mm balloon trocar is introduced. After pneumoperitoneum is achieved at a maximum pressure of 15 mmHg, at high flow, a 12 mm (0 or 30 degrees) hand-held robotic camera is inserted, to assist in placing the other trocars under direct vision. Three 8 mm robotic metallic ports, one 12 mm assistant port, and one 15 mm assistant port (for insertion of endoscopic articulating staplers) are placed. (See Figure 1)

isolated by the use of an Endo-GIA stapler. The restoration of bowel continuity is performed with a stapled side-to-side ileoileal anastomosis. We use a 60 mm and an additional 45 mm Endo-Gia stapler for the side-to-side ileoileal anastomosis. Another, 60 mm Endo –GIA stapler is used transversally, to close the open ends of the ileal limbs. The mesenteric trap defect is closed using running 3-0 vicryl sutures.

Radical cystectomy and bilateral extended pelvic lymph node dissections For the oncological part of the surgery, which includes the radical cystectomy and the bilateral extended pelvic lymph node dissection, it is important to identify three avascular spaces: the periureteral space, the lateral pelvic space and the anterior rectal space.

Once these spaces are identified: 1. The ureters are clipped (Hem-o-lok with vicryl suture attached to them) accordingly, to aid in an exact estimated blood loss count; dilating them for an easier reconstruction of the urinary tract afterwards; and preventing possible cancer cell seeding, specially if ureters are stented prior to surgery. 2. The vascular pedicles can be identified to either staple them with endovascular articulating staplers, or dissect them and secure them with hem-o-loks selectively (when preserving neurovascular structures). 3. The rectum can be dissected away from the posterior bladder wall, the posterior Denonvillier’s fascia can be opened, and the Figure 4 A, B, C: Right Extended Pelvic Lymphadenectomy rectum can be dissected away from the prostate from base to apex under direct vision. intraabdominal pressures, for an easier dissection of Once the posterior dissection is completed, the the lymphatic tissue at this level. Finally, the nodal anterior exposure and apical dissection are performed packages from each side are placed in separate by: 1. Incising the median and medial umbilical Endocatch bags and removed at the end of the ligaments to release the bladder from the anterior procedure. abdominal wall. 2. Opening of the endopelvic fascia bilaterally and suture ligation of the deep dorsal Intracorporeal urinary diversion (Abdominal wall venous complex. Once the proximal membranous and orthotopic) urethra is skeletonized, the urethral catheter is The reconstruction part of the surgery starts by the removed and a Hem-o-lok clip is applied just distal to retroperitoneal transfer of the left ureter to the right the apex to prevent urine spillage. (Figure 2) After side. The posterior attachments (mesocolon) of the incision of the urethra the specimen is placed in a colon are freed beginning at the sacral promontory in retrieval bag and removed from the pelvic cavity. the presacral space providing an unobstructed passage or tunnel. The sigmoid colon is retracted superiorly and anteriorly, and a blunt tip grasper is passed under the surface of the mobilized colon at the level of the sacral promontory. The suture tied to the hem-o-lock attached to the distal ureter is grasped and passed underneath the sigmoid loop and brought to the contralateral side. Pulling on the suture transposes left ureter retroperitoneally from left to right. Care is taken not to twist the ureter nor to cause kinking.

Figure 2: Urethra dissected and clipped

Once the cystectomy specimen is moved away from the pelvic cavity, adequate space is available for a bilateral extended lymph node dissection. We prefer doing the lymphadenectomy after the radical cystectomy. In general, the boundaries of lymph node dissection are well defined in Table 1 (Figure 3 (a,b) and 4 (a,b,c)). Lymphatics are secured with clips.

Occasionally, diminishing the pneumoperitoneal pressures down to 10 mmHg may help in identifying the iliac vein, which is usually flat due to

For an abdominal wall diversion such as an ileal conduit, the bowel including the cecum, ileocecal junction, and ileum is identified. A 20 cm ileal loop segment is isolated about 15 cm proximal to the ileocecal valve by placing marking sutures (3-0 Silk on SH needle for the distal end of the ileal segment and 3-0 vicryl on an SH needle for the proximal end of the ileal segment, where the ureteral intestinal anastomosis is going to be done). The length of the bowel is determined by running the bowel and placing an umbilical tape cut to 15 cm.

Care is taken to maintain good vascularity of the isolated bowel segment by visual inspection of the mesentery, as well as transillumination to help identify the mesenteric vessels. In some cases, we have used also intravenous indocyanine green (ICG) to identify major mesenteric vessels. Once the 20 cm of ileal segment is identified, and the major mesenteric vessels visualized, the segment is Lymph node chain External lliac (1) Obturator (2) Deep Obturator / Hypogastric (3) Common illiac (4) Presacral (5)

Figure 1: Trocar Positioning

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Figure 3 A, B: Left Extended Pelvic Lymphadenectomy

We then put into stretch both ureters by pulling on the sutures attached to the hem-o-loks clipped to both ureters, using the Prograsp forceps. Once the ureters are lined up one next to the other, a 3 cm longitudinal incision is made along the anterior aspect of the distal ends (spatulation), to create a wide anastomosis in a Wallace fashion. This is done using a 4-0 monocryl running suture. Once this is performed we cut the staple line of the proximal end of the ileal conduit segment selected to perform the ureteral ileal anastomosis in a tension-free manner.

First the posterior anastomosis is performed starting proximal at the spatulation site of the right ureter.

Running 4-0 monocryl sutures are used for the anastomosis. A Prograsp stabilizes the Wallace Plate and facilitates the anastomosis in a tension- free manner. (Figure 5)

Figure 5: Wallace type of ureteral ileal anastomosis (Intracorporeal Ileal Conduit)

Prior to completing the anterior layer of the ureteroileal anastomosis, ureteral stents (6 French single pigtail ureteral stents inserted over a 0.035 in. guide wire) are introduced through the distal end of the isolated ileal loop. They are introduced through the assistant port and guided into the ileal conduit using a fenestrated grasping forceps, delivered near the butt end of the loop at the prospective ureteroileal anastomotic site and then advanced into the ureters. Then the ureteroileal anastomosis is completed using 4-0 monocryl running sutures. The distal end of the ileal conduit loop is delivered directly through the anterior abdominal wall through the 8 mm port preselected stoma site. The robotic arm is undocked and a grasping forceps is brought through that trocar and the distal end is grasped. A lunar incision is made around the trocar and the fascia is incised in the form of a cross, as far as that the opening allows a two-finger dilation of the abdominal wall musculature. The conduit end is delivered. Then a rose bud technique is performed to mature the stoma. A 15 JP drain to bulb suction is placed near the ileal-ureteral anastomosis to help detect urinary drainage, through the right lateral 8 mm metallic port.

Intracorporeal orthotopic neobladder For the creation of an intracorporeal neobladder, our preference is to perform a neobladder with great capacity and proven functional results. Since more than five years ago, we have performed a “W” type ileal (60 cm) neobladder described by Hautmann with an additional isoperistaltic 10 cm chimney on the left side of the neobladder. This consists of a total of 70 cm of ileum used. The left ureter is transposed retroperitoneally underneath the sigmoid colon, as describe above, from left to right.

Boundaries of lymph node dissection Proximal - Distal Medial - Lateral Bifurcation of common iliac artery - pelvic floor - midline of external iliac artery - genitofemoral nerve Bifurcation of common iliac artery - pelvic floor - obturator nerve - midline of external iliac artery Origin of obturator nerve - pelvic floor - bladder wall - pelvic side wall including triangle (fossa) of Marcille Aortic bifurcation - Origin of internal and external iliac artery - midline of common iliac artery - genitofemoral nerve Triangle between midline of the common iliac arteries - bifurcation of internal and external arteries, dorsal border is sacrum and medial skeletonization of internal iliac vessels

Table 1: Boundaries of Extended Pelvic Lymph Node Disection Saturday, 17 March 2018

Figure 6: Intracorporeal “W” neobladder presentation and stabilization

The selection of the ileal segment to be utilized is started by placing a 3-0 silk on an SH needle on the ileum, at least 15 cm away from the ileo-cecal valve.

With an umbilical tape cut to 15 cm, measurements of the first, second, third and fourth limbs, are performed and secured by placing 3-0 vicryl stiches on SH needles for identification of each limb of the “W”. At the end of the fourth limb we measure an additional 10 cm for the isoperistaltic limb, and place a 3-0 colored vicryl stitch.

opening of the two first limbs, a 2-0 single needle barbed absorbable suture (V-loc) is used to close the posterior wall of the two opened limbs, in a running fashion. Once this is finished we continue opening the third and fourth limbs at the level of the antimesenteric border of the ileum. We then close the posterior wall again of the neobladder with a running 2-0 V-loc suture, in an organized fashion. A total of three lines of continuos sutures are used to finish closing the posterior wall of the neobladder. (Figure 7 A,B) During all this time, the ileum is stretched and stabilized, facilitating the opening and closure of the posterior wall of the “W” neobladder. Prior to cutting both traction sutures and passing the urethral neobladder neck sutures, a posterior reconstruction of the Denonvillier’s Fascia is performed to bring the urethral stump further into the pelvis (an extra lengthening of the urethral stump of at least 1-2 cm more into the pelvis). This reconstruction is performed with a 3-0 V-loc continuous suture.

Figure 8 A, B: Urethral Neobladder Neck Anastomosis, Anterior Wall Closure and Final Neobladder

Once this is performed, a 2-0 double needle barbed absorbable suture (Quill), is passed through the

We then perform resection and isolation of the 70 cm ileal segment, as described for the intracorporeal ileal conduit technique. After performing a side to side ileal reanastomosis using Endo-GIA staplers, the “W” neobladder is stabilized. The stabilization of the “W” neobladder is facilitated by passing two 0 silk straight keith needles suprapubically percutaneously, and passing them through and through both vertexes of the “W”. This keeps the “W” shaped ileum stretched toward the pelvis. With the third arm, and using a Prograsp, the vicryl stiches placed on the “W” are also grabbed and retracted toward the head.

This perfect stabilization and stretching of the “W” shaped ileum, facilitates the organized opening of the ileum in the antimesenteric border. (Figure 6) The ileum is always opened in a standard organized fashion starting with the right limb of the “W”, and proceeding to the second limb. At the vertex of the “W”, the incision in the antimesenteric boarder (first limb) is brought close to the mesentery, creating a nice wide flap of ileum (2-3 cm in length without stretch and 6 cm wide without stretch) that will be the area where the urethral neobladder neck anastomosis will be done. After finishing the

french single J stent is inserted through the assistant port and passed into the ureter and into the isoperistaltic limb, into the neobladder. Then both stents are passed through the anterior bladder wall of the neobladder. A 3-0 absorbable stich is place to secure both stents to the anterior bladder wall.

Using a Carter Thompson Device passed percutanously, both stents are grabbed and exterioriated through the abdominal wall. The stents are secure to the skin with 3-0 nylon stiches. A urostomy bag is placed to contain the urine drained through the stents.

assistant port. We then pass both needles from outside in, at the level of the neobladder flap created on the right side of the “W”. Once this is done, the percutaneous 0 silk stitches served for traction are cut. This will make the neobladder fall flat into the pelvis on top of the rectum. A urethral neobladder neck anastomosis is performed from outside-in, into the neobladder and from inside-out, into the urethral stump. Both needles are passed twice in the neobladder and the urethra, prior to pulling them bilaterally and approximating the neobladder neck to the urethra. Once this is performed, the anastomosis is completed and prior to closing the neobladder neck anteriorly, a 20 french foley catheter is inserted through the urethra.

(Figure 8 A,B)

Figure 7 A, B: Opening and Suturing of the Posterior Wall of the Neobladder

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After closing the bladder neck with the Quill stich, the anterior wall of the neobladder is closed with a 2-0 V-loc in a running fashion. Prior to closing completely the anterior neobladder wall, a Bricker type of ureteral intestinal anastomosis is performed in the 10 cm isoperistaltic limb on the left side of the “W” neobladder that was not open. Prior to finishing each ureteral intestinal anastomosis, a 6

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Anatomical knowledge Robotic assisted radical cystectomy with intracorporeal urinary diversion is the present in our institution. Strict knowledge of pelvic anatomy, and adherence to oncological principles, enhances oncological results. Intracorporeal reconstruction of the urinary tract, following strict proven open urinary diversion principles, may improve the morbidity of this complex procedure even further.

Editorial Note: Due to space constraints, the reference list can be made available to interested readers upon request by sending an email to: communications@uroweb.org Friday 16 March 08.45-12.15: Urology Beyond Europe, Joint Session of the European Association of Urology (EAU) and the Confederación Americana de Urología (CAU)

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The anterior neobladder wall is closed completely with a 2-0 V loc continuous suture. We then remove the 15 mm assistant port and close the port opening from inside using a 2-0 V loc in a running fashion, to prevent a port hernia. After taking out the Prograsp and undocking the Fourth arm, a 15 round JP drain is passed through the port and placed on top of the fully intracorporeally created neobladder.

After irrigating the abdominal cavity, and securing hemostasis, all robotic instruments are removed and the robot is completely undocked. All specimens are removed in separate Endocatch bags, by extending the 2 cm supraumbilical vertical midline incision to a total of 5 cm.

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Best Abstracts: First prize winners British study bags oncology prize while a multi-centre study from France tops non-oncology Editorial Note: We are re-printing here the unedited and original prize-winning abstracts submitted to this year’s congress. Congratulations to all the authors and researchers for their innovative work, insights and contributions to urology.

Authors: A. Chebbi, A. Giwerc, Results B. Peyronnet, L. Freton, J. Olivier, Among a total of 1500 kidney trauma over the studied Q. Langouet, M. Ruggiero, period 268 patients met the inclusion criteria. The I. Dominique, C. Millet, S. Bergerat, median age was 25 years and 158 (79%) patients P. Panayotopoulos, R. Betari, were male. Clinicians performed an ED with ureteric X. Matillon, T. Caes, P. Patard, Results stent insertion for 69 patients (26%). A persistent UE A. Chebbi N. Szabla, N. Brichart, L. Sabourin, was found in 50 patients (36%) of the CM on the First Prize for the Best Abstract (Oncology) Between 31st May 2012 and 5th September 2017, 248 K. Guleryuz, C. Dariane, C. Lebacle, repeat CT in mean delay of 6 days. This persistent leak Abstract No: AM18-0618 patients were randomized (123 surveillance; 125 J. Rizk, A. Gryn, F. Madec, M. Hutin, B. Pradere, Results of POUT - A phase III randomised trial of chemotherapy) at 57 UK centres. In October 2017, the required a delayed ureteric stent insertion in 23 peri-operative chemotherapy versus surveillance in independent trial oversight committees recommended C. Pfister, G. Fiard, F. Nouhaud (Rouen, Rennes, Lille, patients (17%). The mean length of staywas longer Tours, Paris, Lyon, Clermont-Ferrand, Strasbourg, upper tract urothelial cancer (UTUC) POUT close to recruitment as data collected thus far after ED 21 days vs. 14 days after CM (p=0,03). There Angers, Amiens, Toulouse, Caen, Nantes, Montpellier, was no difference in complications rate and death (data snapshot 5th September 2017) met the early Authors: A. Birtle, M. Johnson, Grenoble, France) stopping rule for efficacy. At the time of interim related to the trauma between the 2 groups.

R. Kockelbergh, F. Keeley, J. Catto, analysis, median follow-up was 17.6 months (IQR Introduction & Objectives R. Bryan, J. Chester, R. Jones, 7.5-33.6). Patients had median age 69 years (range Conclusions Management of non-penetrating renal trauma (NPRT) Our results suggest that CM should be considered for M. Hill, J. Donovan, A. French, 36-88), 30% pT2, 65% pT3; 91% pN0. Grade ≥3 associated with urinary tract rupture (AAST Grade C. Harris, T. Powles, R. Todd, toxicities were reported in 60% chemotherapy the management of renal trauma associated with IV-V) is not clearly codified regarding the usefulness L. Tregellas, C. Wilson, A. Winterpatients and 24% surveillance patients. During the urinary extravasation at the initial CT-assessment. CM A. Birtle of upper tract drainage with stent insertion. The aim bottom, R. Lewis, E. Hall (Preston, treatment period the most common grade ≥3 [≥4] was associated with good outcomes as 83% of the Newcastle upon Tyne, Leicester, toxicities in chemotherapy patients were neutropenia of this study was to compare the outcomes of an early patients didn’t required any drainage of their upper upper urinary tract drainage (ED) to a conservative Bristol, Sheffield, Birmingham, Cardiff, Glasgow, 29% [5%] (vs. 0% surveillance) and tract and the urinary extravasation at repeat CT was management (CM) after a NPRT with a urinary London, Southend, Chinnor, United Kingdom) thrombocytopenia 7% [6%] (vs. 0%). 47/123 still present for 36% of the patients only. Initial extravasation (UE) at initial CT-scan assessment. (surveillance) and 29/125 (chemotherapy) DFS events clinical monitoring and repeat CT-scan to re-assess Introduction & Objectives were reported; unadjusted HR = 0.47 (95% CI: 0.29, the urine leak might be useful and less invasive than The role of post nephro-ureterectomy treatment for 0.74) in favour of chemotherapy (log-rank p= 0.0009). Materials & Methods a systematic ED. A multicenter retrospective national study UTUC is unclear. POUT (CRUK/11/027; NCT01993979) is Two year DFS was 51% for surveillance (95% CI: 39, was conducted, including all patients a UK led trial that addresses whether adjuvant 61) and 70% for chemotherapy (95% CI: 58, 79).

Table: Results after NPRT with urinary extravasation chemotherapy improves disease free survival (DFS) for Metastasis-free survival also favoured chemotherapy: treated for renal trauma in 16 centers from 2005 to 2015. Patients who had patients with histologically confirmed pT2-T4 N0-3 HR = 0.49 (95% CI: 0.30, 0.79, p=0.003). a UE at the initial CT-scan assessment M0 UTUC. delayed phase were considered for Conclusions inclusion. Penetrating traumas, Materials & Methods Adjuvant chemotherapy is tolerable and improved hemodynamically unstable patients Patients (maximum n=345), WHO performance status metastasis-free survival in UTUC. Recruitment to the and those who were initially treated 0-1, ≤90 days post NU were randomised (1:1) to 4 POUT trial was terminated early because of efficacy cycles of gemcitabine-cisplatin (gemcitabinefavouring the chemotherapy arm; follow up for overall with nephrectomy were excluded.

Patients were divided into 2 groups: carboplatin if GFR 30-49ml/min) or surveillance with survival continues. POUT is the largest randomised ED defined by drainage of upper chemotherapy given on recurrence if required. trial in UTUC and its results support the use of urinary tract of the injured kidney Patients had 6 monthly cross sectional imaging and adjuvant chemotherapy as a new standard of care. within the 48 hours following the cystoscopy for the first 2 years, then annually to 5 admission and CM. The persistence of years. Toxicity was assessed by CTCAE v4. The primary First Prize for the Best Abstract (Non-Oncology) UE at repeat CT-scan, the need for endpoint was DFS. The trial was powered to detect a Abstract No: AM18-3773 delayed drainage, length of stay, hazard ratio (HR) of 0.65 (i.e. improvement in 3 year Is systematic early drainage relevant to treat urinary complications rate and specific death DFS from 40% to 55%; 2-sided alpha=5%, 80% tract rupture in non-penetrating renal trauma? Results related to the trauma were analyzed. power) with Peto-Haybittle (p<0.001) early stopping from a multicenter study rules for efficacy and inefficacy. Secondary endpoints included metastasis-free survival, overall survival, toxicity (CTCAE v4) and patient reported quality of life (assessed by EORTC QLQ-C30 and EQ5D).

Interactive, Insightful and Independent Education

STEPS Sessions To Evaluate luate ProgresS Progres o in the management of urological cancers

Learning from Experts in Onco-Urology Applications now open!

Visit Ipsen booth E15 during EAU18 to learn more

What is STEPS? STEPS, or “Sessions To Evaluate ProgresS in the management of urological cancers”, is a programme specifically designed for recently specialised onco-urologists who want to learn directly from worldleading experts in bladder, prostate, renal and testicular cancers.

The CME-accredited programme is a fundamental part of the EAU/ ESOU strategic partnership with Ipsen. It is founded on our shared commitment to the education of young urologists.

Bringing together a multinational group of medical professionals across several areas of expertise, and with different experiences, allows the fellows to see a variety of new treatment possibilities.

It can highlight the pitfalls and solutions provided by diverse approaches. It also opens the door to creating international ties among medical practitioners, and a networking opportunity that can prove invaluable for the careers of young clinicians.

“STEPS connects younger urologists from different countries – it’s very interactive with lots of new information and data discussed” STEPS fellow 2018

To date, 20 different internationally recognised experts, supported by the ESOU Board, have inspired 138 fellows from 29 countries – and our objective is to continue supporting STEPS to help improve the management of all patients with urological cancers.

Who should apply?

Recently specialised clinicians with a firm interest in the management of urological cancers, who: - Can demonstrate support from their Head of Department

Next event: Meet-the-Expert Session during the 16th Meeting of the EAU Section of Oncological Urology (ESOU) Saturday 19th January 2019 Prague, Czech Republic

- Are keen to participate in ESOU and EAU programs - Understand and speak English fluently “Within STEPS I really like the enthusiasm of the delegates and the interaction I can have with them as an expert” Peter Mulders, STEPS mentor 2018

Find out more about STEPS from the ESOU website: http://uroweb.org/section/esou/information/

TRI-ALL-000297

T115 STEPS Advert 270 x 194.3.indd 1

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EUT Congress News

ESOU is an independent 3rd party meeting. Travel, accommodation, registration and subsistence costs are supported by Ipsen.

16/02/2018 09:27

Saturday, 17 March 2018

ESU Masterclasses: Designed and aimed to educate Participants’ feedback is crucial to continually improve the masterclass format Dr. Joan Palou Chairman, European School of Urology Dept. of Urology Fundació Puigvert Barcelona (ES)

Progress is inevitable; what we know now as urologists in terms of research, technologies and procedures will eventually need an upgrade. We need to grow alongside this advancement, for our patients and for our practice. Hence, the inception of the European School of Urology (ESU).

ESU’s primary goal is to increase what we know and to broaden our skills through various activities designed to meet our educational needs while taking our challenging schedules into account. The high-level ESU Masterclasses are one of the ESU’s most prominent activities.

Why choose the masterclass format?

Although ESU Courses offer frontline lectures, the ESU Masterclasses, in collaboration with the EAU sections of the EAU, are created to be more in-depth. These masterclasses cover urolithiasis, non-muscle-invasive bladder cancer, to focal therapy, among other topics. The ESU Masterclass format is a consolidation of cutting-edge lectures, typical or sometimes challenging clinical cases, and informative semi-live and live surgeries. The programme also feature riveting discussions and hands-on demonstrations.

Even the setting is conducive to learning. Each Masterclass has a defined number of participants – small enough for optimal learning for good, solid interactions and large enough for productive brainstorming. Its commendable faculty is comprised

Benefits for the participants Completion of an ESU Masterclass means improved proficiency of participants in terms of practical diagnosis, specific techniques, decision-making and management.

of top experts who provide the best and the latest updates in their respective fields.

ESU Masterclasses At present, there are seven Masterclasses which are as follows: • ESU-ESUT Masterclass on Operative management of Benign Prostatic Obstruction focuses on relevant, minimally-invasive alternatives for BPO treatment;

The feedback received from each Masterclass continue to show overall satisfaction from participants. They indicated noticeable improvements with their skills and a boost in their clinical practice after incorporating take-home messages and concepts.

• ESU Masterclass on Female and Functional Reconstructive Urology covers the management of functional disorders such as lower urinary tract diseases, and other diseases that affect the pelvic floor and related organs;

Up-to-date, practical tips and tricks they have acquired from the Masterclasses greatly benefitted their patients.

• ESU-ESUT-ESUI Masterclass on Focal therapy for localised prostate cancer provides a comprehensive review of the rationale for FT and the modalities of patients selection;

A pre-test and post-test are implemented to boost quality and to evaluate the efficacy of the masterclasses and the faculty (what works and what needs improvement), and to gauge the knowledge of participants

A Hands-on Training session at the BPO Masterclass

• ESU-ESUT Masterclass on Lasers in Urology offers • ESU-ESOU Masterclass on Non-Muscle-Invasive the mastery of basic concepts of each laser Bladder Cancer delivers modern techniques of treatment, identification of suitable candidates transurethral surgery from en-bloc resection, new per approach, and management of complications; imaging technologies to new generation equipment; • ESU-Weill Cornell Masterclass in General urology has a three-year rotation programme. This year, the masterclass will focus on stone management, urothelial cancer update, and paediatric urology;

Plans There is a steady increase in the demand for ESU Masterclasses since its establishment and up to this day. This is truly encouraging. Through these Masterclasses, participants are given the opportunity to access the best resources in urology. The ESU aims to expand starting next year the number of topics to meet increasing demand.

• ESU-ESUT Masterclass on Urolithiasis is comprised of theoretical courses on stone disease: pathophysiology, diagnosis and conservative treatment of lithiasis, and extracorporeal and interventional management;

Full house at the opening of the 1st ESU-ESOU Masterclass of NMIBC (Photo by Dr. Fadi Dalati)

• ESU-ESTU Masterclass on Kidney Transplant is the latest installment to the masterclass series designed to offer high-level theoretical and practical training, and detailed updates on kidney transplantation.

All eyes on Prof. E. Liatsikos at the Urolithiasis Masterclass

EAU Member Benefits at EAU18!

Cutting-edge Science at Europe’s largest Urology Congress

EAU members are kindly invited to the EAU Booth H69 in the Red Area to collect the following complimentary items: EAU Extended Guidelines The EAU Extended Urological Guidelines edition 2018.

EAU Pocket Guidelines The pocket version of the EAU Guidelines edition 2018.

Are You Not done Watching?

Surgery in Motion School presents you with a selection of the best Live Surgeries from EAU18

European Association of Urology

Historia Urologiae Europaeae series is addressed to all European urologists. Its aim is to make known the ideas and the work of our predecessors, and to help us understand the current trends in the development of our speciality.

Unfortunately, the treatises written in Sanskrit, ancient Chinese, Greek and Latin are both difficult to find and difficult to understand, and should, therefore, be translated into English. The same applies to more recent books published in various languages.

Guidelines 2018 edition

Most of the treatises produced before the 17th century, even the legendary ones, have gaps, mistakes and inconsistencies. Modern scientific research allows us to re-evaluate this ancient knowledge and examine it from new perspectives. The History Office of the EAU in collaboration with internationally based urologists, historians, philologists and other experts, conducts research, accumulates and shares this fascinating information in their annual publication, Historia Urologiae Europaeae.

“Remember the days of old, consider the years of many generations, ask thy father, and he will shew thee; thy elders, and they will tell thee.”

(Deuteronomy 32:7)

MINIMAL SYSTEM REQUIREMENTS Windows PC * Windows Vista / 7 / 8 / 10 Macintosh * OS X 10.5 and newer (Intel) Installation of Adobe Acrobat Reader to open PDF presentations.

USAGE Insert the DVD-ROM in the DVD tray of your computer.

If the application does not start automatically, please open the Explorer or Finder, go to your Disc Drive and run the “ESUCOURSES2018” Application.

Some information contained in this DVD may cite the use of products in a dosage, for an indication, or in a manner other than recommended.

Before prescribing the product always refer to the prescribing information available in your country.

For more information: EAU Education Office PO Box 30016, 6803 AA Arnhem, The Netherlands T +31 (0)26 389 0680 esu@uroweb.org, www.uroweb.org

BARCELONA

15-19 March 2019

EAU18 Posters DVD A DVD containing posters presented during the 33rd Annual EAU Congress.

A copy of the EAU18 Posters DVD is distributed in the congress bag.

EAU18 ESU Courses www.eau18.org

Supported by

MINIMAL SYSTEM REQUIREMENTS Windows PC * Windows Vista / 7 / 8 / 10 Macintosh * OS X 10.5 and newer (Intel) Installation of Adobe Acrobat Reader to open PDF presentations.

USAGE Insert the DVD-ROM in the DVD tray of your computer.

If the application does not start automatically, please open the Explorer or Finder, go to your Disc Drive and run the “POSTERS2018” Application.

Some information contained in this DVD may cite the use of products in a dosage, for an indication, or in a manner other than recommended.

Before prescribing the product always refer to the prescribing information available in your country.

For more information: European Association of Urology PO Box 30016, 6803 AA Arnhem, The Netherlands T +31 (0)26 389 0680, F +31 (0)26 389 0674 eau@uroweb.org, www.uroweb.org

BARCELONA

15-19 March 2019

Join us!

EAU18 Posters www.eau18.org

www.eau18.org

Supported by an educational grant from

DE HISTORIA VOLUME

Omslag GL 2018.indd 1

Saturday, 17 March 2018

EAU18 ESU Courses DVD A DVD including all presentations and course materials of the ESU Courses given during the Join us! congress can be collected at booth E11 in the Red Area.

UROLOGIAE EUROPAEAE European Association of Urology 2018

surgeryinmotion-school.org

EAU18 Abstracts USB A USB containing all presented abstracts during the 33rd Annual EAU Congress can be collected at booth G01 in the Red Area.

www.eau18.org

For this relief, much thanks!

The new publication by Dr. Johan Mattelaerew explores the depiction of urination in art, both classical and contemporary. It is a beautifully illustrated coffee table book that celebrates our field and offers unique insights. The book can be picked up at the EAU Booth H69 in the Exhibition with the appropriate entitlement and on a first come, first served basis.

DE HISTORIA UROLOGIAE EUROPAEAE 25

Improve your surgical skills With top notch videos of urological procedures By the best surgeons in the world

De Historia Urologiae Europaeae Vol. 25 The EAU History Office is presenting a special, anniversary edition of De Historia this year, with contributions from every past Editor. Features a wide range of interesting biographies, new research and personal stories from the history of our field.

Congress delegates are kindly invited to collect the following complementary items:

25

EDITED BY PHILIP VAN KERREBROECK, DIRK SCHULTHEISS AND JOHAN MATTELAER 22-01-18 11:00

Surgery in Motion School is a collaboration of

EUT Congress News

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90% of our patients were recorded to have an increase in EDITS score 69.7, p< 0.001.

Low-intensity ESWT An Asian tsunami breaking the horizon Dr. Colin Teo Dept. of Urology Khoo Teck Puat Hospital Singapore (SG)

The use of Low-intensity shockwave therapy(LiESWT) in urology has been making waves in Asia. In the short span of the last few years, we see a rising trend in the use of LiESWT in Asia as more machines and available models are acquired by many urology practice.

We see an increasing confidence in patient outcomes encouraging more Asian urologists to embrace and include Extracorporeal Shockwave Therapy (ESWT) in their armamentarium to manage patients with Erectile Dysfunction (ED) and Chronic Pelvic Pain Syndrome (CPPS).

Therapeutic usage of ultrasound has been around for many years. It was first used in the 1960s by sports therapists and orthopaedic surgeons for soft tissue injuries. Its effects were thought to be mediated by direct simulation of healing and neovascularisation.

It achieved widespread use in tendon injuries such as plantar fascitis and patients with chronic pain1.

Over the next few decades, the use of therapeutic ultrasound had spread widely. Urologists have vast experience with the use of Extra-corporeal Shockwave Lithotripsy (ESWL) for the treatment of stones, which is a prime example of the use of ultrasound for therapeutic purposes since it was first used on a human subject in February 1980. Fast forward to today, ESWT has come a long way since it was first conceived. It all began in mid-2000s when medical literature from our colleagues in the cardiovascular field showed during in-vitro studies that ultrasound could enhance the expression of vascular endothelial growth factor (VEGF) and its receptor, Flt-12.

Another study conducted on rats showed that the application of low energy shockwave therapy led to increased recruitment of circulating endothelial progenitor cells, thus facilitating the onset of neovascularisation and angiogenesis. Further studies among human subjects demonstrated its vascular effects within the myocardium as well as in patients with diabetic foot ulcers3,4.

Pioneering ESWT studies It was against this background of studies that one of the pioneering studies for ESWT was performed by a urologist with the Medispec model. Vardi et al published their study in April 2010 in the EAU journal, thus breaking the first ground for the use of ESWT in the treatment of ED5. This was a prospective trial of 20 men with vasculogenic ED who were treated with ESWT. The results showed significant increases in IIEF scores, duration of erection and penile rigidity. Ten men from the study did not require any PDE5 (phosphodiesterase 5)-inhibitor after the treatment.

Gruenwald and team also clearly showed the efficacy of ESWT with an open label single-arm prospective study of the use of ESWT with ED patients6. At the end of the study, they recorded results showing a significant increase in IIEF scores, with 72.4% of the subjects achieving an EHS ≥3, therefore allowing for intercourse. Both studies subscribed to a treatment protocol of two times a week for three weeks, followed by a repeat session after a three-week break.

By 2012, the two European studies had garnered keen interest in ESWT as a rising novel potential and non-invasive therapy for the treatment of ED with no significant adverse effects. Since then, Chung et al7 from Australia subsequently published a paper in 2015 which recruited 30 patients who had previously tried and failed a trial of oral PDE5-Inhibitors. 60% of the patients reported an improvement of at least 5 on their IIEF scores at the end of the study, with 67% of them being satisfied with ESWT using the Storz machine.

In this study, the treatment protocol consisted of two sessions a week for six weeks in a row.

ED treatment in Asia Over the last few decades, Asia has seen explosive growth in population and a burgeoning middle class as well as aging populations in many of its affluent countries. With longer lifespans and more affluent 30

EUT Congress News

lifestyles, cardiovascular disease is slowly becoming a focus for most countries. A paper published in 2011 estimated the prevalence of ED in Asia varies between 9% and 73%10. Over the last few decades, taboos about sexual disorders have also been slowly eroded, leading men to be more forthcoming in seeking help for erectile dysfunction. Compared to a decade ago, urologists in Asia are starting to see more patients willing to seek treatment with ED. Within Asia however, unique challenges lie in addressing the treatment of ED with ESWT. Culturally, significant weight is placed by patients on traditional and alternative treatments. Men who are frustrated by the lack of efficacy with PDE5-inhibitors often turn to acupuncture or other alternative therapies in a bid to gain results. We are beginning to see a surging demand and interest in ESWT in many Asian countries where we see an increase in ESWT machines not just in numbers, but in the different models being used by urologists. We also see an increasing trend amongst General Practitioners with specialist interest in Men’s Health seeking to provide this service to their patients.

Driving this growth are the positive anecdotal patient feedback and results from Asian studies which have fanned the confidence in ESWT in Asia.

Asian studies Asian studies included a study In India8 in 2015 of two randomised groups of patients who were assigned to either 12 sessions of ESWT or placebo therapy. It showed positive results in both IIEF and EHS scores among its patients. Most recently, a study conducted in Guangzhou9, China compared two groups of patients who were randomised to either ESWT treatment or usage of a vacuum erectile device (VED) also concluded that ESWT was comparable to the use of a VED in the treatment of ED8. On-going research by Dornier MedTech in Singapore continues to study on translating the tissue effects of ESWT on 1. Vacular healing and angiogenesis. 2. Stem cell recruitment and activations. 3. Nerve cell activation and repair. 4.

Immune regulation.

CPPS Treatment While ED seems to be a driving demand, many patients suffering from CPPS are also seeing good treatment responses and the cross application of ESWT for CPPS also provides the acceptance by many urology practices towards acquiring ESWT machines.

For CPPS patients, Guu et al11 In Taiwan reported in their study that 27 of the 33 patients (81.82%) had a successful response to Li-ESWT, with a decrease of 3.29 and 5.97 in the VAS score and total IPSS at the three-month follow-up while Zeng et al12 in China reported that 71.1% of CPPS patients on ESWT exhibited perceptible improvement in total NIH-CPSI compared with 27.0% of the control group (P < 0.001).

Singapore Over the last three years in Singapore, there has been an increase in the number of machines and the range of available models from Storz, Medispec and Dornier used for the treatment of ED, CPPS and painful bladder syndromes both in public and private institutions. First started by Prof Peter Lim in Parkway Gleneagles Hospital, he has already treated more than 200 patients on the in the region in private healthcare with the Medispec ED1000 machine . Three out of the seven public hospital institutions have since also started providing ESWT treatment to their patients.

In our institution, we recruited 14 local patients with erectile dysfunction and assigned them to treatment with ESWT using the Storz Duolith machine. We evaluated treatment outcomes with IIEF scores and EHS scores. Patient satisfaction based on EDITS scores were also recorded. Our results at the end of 12 sessions showed an increase in the mean IIEF scores from 11.9 to 17.3, with a p-value of 0.03. 82% of patients had improvements with IIEF scores, with 54% achieving at least a five-point increase in IIEF scores. 63% of our patients achieved treatment success with an EHS score ≥ 3, allowing for penetration during intercourse. 90% of our patients were recorded to have an increase in EDITS score from 51 to 69.7, p< 0.001. With strong positive feedback from patients, we will next evaluate the Dornier Aries 2 machines as patients continue to benefit from ESWT in ED, CPPS and painful bladder syndromes.

Moving forward, the use of ESWT by urologists in Asia is likely to contin growth and Asian patients will enjoy greater access to ESWT. In the sho

pharmaceutical method of treatment of ED which we can bring to our patients. With more studies and understanding in ESWT technology, we hope to see improvements in outcomes with new treatment protocols that will benefit our patients with ED and CPPS. The question to ask now is, ‘ Will you be caught up in this ESWT wave as it rides across Asia?’

Surg Res 2009;152:96–103.

5. Yoram Vardi *, Boaz Appel, Giris Jacob, Omar Massarwi, Ilan Gruenwald. Can Low-Intensity Extracorporeal Shockwave Therapy Improve Erectile Function? A 6-Month Follow-up Pilot Study in Patients with Organic Erectile Dysfunction. Eur Urol. 2010 Aug;58(2):243-8.

6. Gruenwald I1, Appel B, Vardi Y. Low-intensity extracorporeal shock wave therapy--a novel effective treatment for erectile dysfunction in severe ED patients who respond poorly to PDE5 inhibitor therapy. J Sex Med. 2012 Jan;9(1):259-64.

References 1. Angela Notarnicola et al. The biological effects of extracorporeal shock wave therapy (eswt) on tendon tissue. Muscles ligaments tendons J. 2012 Jan-Mar; 2(1):33-37.

2. Nurzynska D, Di Meglio F, Castaldo C, et al. Shock waves activate in vitro cultured progenitors and precursors of cardiac cell lineages from the human heart. Ultrasound Med Biol 2008;34:334–42 3. Kikuchi Y, Ito K, Ito Y, et al. Double-blind and placebocontrolled study of the effectiveness and safety of extracorporeal cardiac shock wave therapy for severe angina pectoris. Circ J 2010;74: 589–91.

4. Wang CJ, Kuo YR, Wu RW, et al. Extracorporeal shockwave treatment for chronic diabetic foot ulcers. J

Editorial Note: Due to space constraints the reference list has been shortened. Interested readers can email at communications@uroweb.org to request for the full list.

Friday 16 March 09.15-12.15: Urology Beyond Europe; Joint Session of the European Association of Urology (EAU) and the Federation of ASEAN Urological Associations (FAUA)

28 - 31 August

Leading Continence Research and Education Call for Abstracts: 1 March - 3 April International Continence Society 48th Annual Meeting www.ics.org/2018

Alan J. Wein

Diane Newman

Roger R. Dmochowski

Lori Birder

Co-Chairman

Chairman

Scientific Co-Chair

Scientific Co-Chair

*

*

Riding the Asian Tsunami Moving forward, the use of ESWT by urologists in Asia is likely to continue its growth and Asian patients will enjoy greater access to ESWT. In the short span of less than 10 years since Vardi et al published their paper about ESWT, we now have a non-invasive, nonSaturday, 17 March 2018

Shared decision-making in prostate cancer care Encouraging patient’s role in decision-making or ensuring their preferred level of involvement?

Marie-Anne Van Stam, MSc Dept. of Urology The Netherlands Cancer Institute, Amsterdam (NL)

Imagine you informed Jack, a patient with localized prostate cancer, about his treatment options. After you discussed the benefits and side-effects of the options, Jack asks you to make the treatment decision. What do you do? Do you encourage Jack to be actively involved in treatment decision-making?

Or do you suggest a treatment to ensure that the patient plays the decision-making role he prefers?

If you consult the literature about this dilemma, you will find conflicting results. Several studies suggest that patients who prefer either more or less involvement in decision-making than they actually experience have worse decision- and health-related outcomes than those for whom their preferred and experienced role match1. But other studies concluded that patients who are actively engaged in their decisions, regardless of role preferences, have better care experiences2.

To examine which of these strategies resulted in the most positive outcomes in a sample of patients with localized prostate cancer, we performed a prospective, multi-centre, observational study. We investigated whether active involvement in decision-making regardless of role preferences, or concordance between preferred and experienced role is the strongest predictor of more favourable patient-reported outcomes. About 450 patients with localized prostate cancer answered questions about their preferred role in decision-making (before treatment) and about the role they experienced (three months after treatment).

The large majority of patients (89%, n=403) preferred active involvement in decision-making, with the remaining 11% (n=51) indicating a preference for passive involvement. A similar distribution was observed for the experienced role in decision-making (active involvement=87%, n=393; versus 13% passive involvement, n=61).

Most patients (n=376, 83%) experienced a role in decision-making that matched their preferred role.

However, more than half (67%) of the patients who preferred passive involvement reported having experienced active involvement (preferred less involvement than experienced, n=34). Conversely, of those who preferred active involvement, 11% experienced passive involvement (preferred more involvement than experienced, n=44).

“These findings indicate that patients with localized prostate cancer who indicated that they had been actively involved in treatment decisionmaking were better informed about their cancer and its treatment, experienced less uncertainty about the treatment decision...”

Active involvement was associated significantly with more prostate cancer (PC) knowledge (Cohen’s d=0.30), less decisional conflict (d=0.52), and less decisional regret (d=0.34). Role concordance was not associated significantly with PC knowledge or decisional regret. However, we did observe an association with decisional conflict (d=0.41), indicating that patients who preferred more involvement than they experienced had more decisional conflict when compared to those who initially preferred less involvement or those who experienced a match between their preferred and experienced role.

These findings indicate that patients with localized prostate cancer who indicated that they had been actively involved in treatment decision-making were better informed about their cancer and its treatment, experienced less uncertainty about the treatment-decision, and had less regret about the chosen treatment, compared to patients who reported having experienced passive involvement. Our results do not support previous studies that reported that a match between decision-making preferences and experienced role results in more favourable health care experienced.

In summary, while it may seem desirable to tailor the patients’ role in decision-making to their initial preference, and particularly to a preference for deferring to the advice of the clinician, this does not result in less decisional conflict or regret. Rather, in patients with localized prostate cancer, our results support a strategy of shared decision-making to increase patients’ knowledge about their disease and its treatment, their sense of certainty about the treatment decision, and their satisfaction with the chosen treatment.

Study Members: M.A. Van Stam, MSc; A.H. Pieterse, PhD; H.G. Van Der Poel, PhD, M.D.; J.L.H.R. Bosch, PhD, M.D.; C.N. Tillier, MANP; S. Horenblas, PhD, M.D.; N.K. Aaronson, PhD References 1. Brom L, Hopmans W, Pasman HRW, Timmermans DR, Widdershoven GA, Onwuteaka-Philipsen BD. Congruence between patients’ preferred and perceived participation in medical decision-making: a review of the literature.

BMC Med Inform Decis Mak. 2014;14(1):25. doi:10.1186/1472-6947-14-25.

2. Kashaf MS, McGill E. Does Shared Decision Making in Cancer Treatment Improve Quality of Life? A Systematic Literature Review. Med Decis Mak. 2015;35(8):1037-1048. doi:10.1177/0272989X15598529.

Saturday, 17 March 14.15-15.45: EAUN Thematic Session 5: Shared decision making: Putting patients at the heart of urology care, Green Area Room 11 (Level 1) Friday, 16 March 2018, 10:45 - 12:15 Poster session 06: AM18-2341: “Encouraging every patient to be actively involved in decision-making, or ensuring patients’ preferred level of involvement” Room: Blue Area, Room 5 (Level 0)

Platinum Picture Perfect Please come to the European Urology booth #C3-C29 and have your Platinum Postcard created and posted online.

Daily from 10.00 to 18.00

europeanurology.com eufocus.europeanurology.com europeanurology.com/euoncology

Saturday, 17 March 2018

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THE AIS CHANNEL: PHYSICIAN EDUCATION ANYWHERE, ANYTIME. Boston Scientific is pleased to announce a new partnership with the Advances in Surgery (AIS) Channel, the new online platform with live interaction for surgical education. AIS programming shares the latest surgical techniques from leading surgeons with professionals in the scientific community. Content is complimentary, available on any Internet-enabled device, with the goal of bringing accessible surgical education to everyone.

Visit Boston Scientific booth #F15 at EAU to experience the first AIS Channel Urology transmissions:

Penile Prosthesis Implantation

Saturday 17 March 16:00 | Live moderated pre-recorded case Monday 19 March 10:00 | Pre-recorded case

by Dr Ignacio Moncada (Madrid)

GreenLight™ Enucleation Sunday 18 March, 10:00 and 15:00 Live moderated pre-recorded case

by Dr Fernando Gómez-Sancha (Madrid)

All cited trademarks are the property of their respective owners. CAUTION: The law restricts these devices to sale by or on the order of a physician. Indications, contraindications, warnings and instructions for use can be found in the product labelling supplied with each device. Information for the use only in countries with applicable health authority product registrations. This material is not for use in the U.S., France and Japan. © 2018 Boston Scientific Corporation or its affiliates. All rights reserved. UROPH-530801-AA FEB2018

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EUT Congress News

www.bostonscientific.eu

Saturday, 17 March 2018