EUT Congress News - Sunday 17 March

European Urology Today

EUT Congress News

TFhi risrdt EEdd iittiio onn

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

Monday, Saturday,19 25March March2018 2017

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

Benefits of upfront PET-CT use still unclear Plenary Session 3 evaluates new diagnostics for oligometastatic PCa

By Loek Keizer

leaving Mottet to give the audience at the eURO Auditorium the perspective of the most current EAU Guidelines. The Guidelines considers PET PSMA ‘of interest’, despite the lack of evidence of effectiveness for upfront staging. Targeting the metastases, as De Meerleer advocated for, is considered ‘experimental’, and interesting to evaluate.

“Nobody knows yet if using PET-CT upfront is beneficial, or if picking up small traces of the disease can lead to patient improvement in survival and outcomes. We know from some series that there might be a place for such imaging techniques, but certainly not for all patients. It can be a waste of money and time,” Prof. Alberto Briganti (IT) cautioned during Plenary Session 3.

The third day of EAU18 started with a well-attended Plenary Session on prostate cancer. The session included several case-based debates, an overview of the most important PCa-related posters and the ESMO lecture. The main session was preceded by a short “Game-changing session”, which featured an update on immunotherapy in renal cell and bladder cancer, and a talk on the new standard of care for hormone-sensitive PCa. Case-based debate on PET-CT The majority of Plenary Session 3 was dedicated to a multidisciplinary case-based debate on PET-CTdetected oligometastatic disease, moderated by

The case-based debate on PET-CT-detected oligometastatic disease is moderated by Prof. Briganti (left).

Briganti. It featured contributions from Prof. Silke Gillessen Sommer (CH) from the perspective of an oncologist, Prof. Steven Joniau (BE) as a urologist, Prof. Gert De Meerleer (BE) as a radiation therapist and finally Prof. Nicolas Mottet (FR) for the EAU Guidelines perspective.

classified as cN0, M0 through conventional imaging, but where the use of a PSMA PET-CT revealed a spread to a lymph node in the pre-sacral area and two bone lesions, both smaller than 1cm. This raised the patient’s status to cN1 and cM1.

The case as presented to the panel by Briganti concerned a 61-year-old patient who was

Profs. Gillessen Sommer, Joniau and De Meerleer argued treatment options from their perspective,

“We saw a nice multidisciplinary discussion, which allowed the audience to see possible treatment options from different perspectives,” Briganti summarised. “Of course we always need evidence first, but there is certainly a role for expert opinion. We are waiting for strong evidence yet to come.”

On the timeframe of possible strong evidence for the advantage of upfront use of PET-CT, he said: “We might never even see it. We are currently using PSMA, but in a few years or even months, we might have a better tracer. It’s a constantly evolving field.”

See related story on Page 2... Better PCa detection...

LUTS: Individualised care offers improve QoL Plenary Session 4 examines tailored LUTS management

By Erika de Groot Urodynamics, the link between LUTS and progressive neurogenic disease, and polypharmacy were some of the topics deliberated during the well-attended Plenary Session 4 “Contemporary storage Lower Urinary Tract Symptoms (LUTS) management”, which was chaired by Prof. F.C. Fiona Burkhard (CH) and Prof. Chris Chapple GB).

Urodynamics “In neurology, there are two main goals: to protect the upper urinary tract and to improve the patients’ quality of life,” stated Prof. Dr. Thomas Kessler (CH). In his lecture “Lower Urinary Tract Symptoms (LUTS) and stable neurogenic disease”, he defined Urodynamics as a tool to assess the function of the lower urinary tract

and to secure the upper urinary tract. Kessler said, “Solving a patient’s symptoms does not also mean also saving the upper urinary tract.”

According to Kessler, neurourology is a balancing act.

“You have to individualise the management of your patients. Can the patient walk without assistance or is he in a wheelchair? But even then, the latter could have a very active lifestyle. Customised treatment is key; one size does not fit all.”

Progressive neurogenic disease “LUTS change as the patient’s conditions evolve,” said Dr. Xavier Gamé (FR) in his lecture “LUTS and progressive neurogenic disease”. Gamé added that adapted management to different symptoms are available. He stated that follow-up is required to

assess LUTS changes and to screen complications in MS patients.

Polypharmacy According to Dr. Adrian Wagg (CA), there is little evidence on the link between polypharmacy and overactive bladder (OAB), but more for undifferentiated incontinence.

“Polypharmacy makes urinary incontinence more likely,” said Wagg. In his lecture “Age, polypharmacy and OAB”, he stated that when OAB drugs and other antimuscarinics are combined, these contribute to an overall anticholinergic burden. He said that this should be reduced where possible. Additionally, Wagg said that a formal, contextual medication review may help.

Prof. Kessler makes a point on LUTS management

eUROGEN: Improving lives for patients with rare diseases European Reference Network is top performing in EU

By Jen Tidman The European Reference Network (ERN) eUROGEN is already the most proactive of the 24 ERNs approved and funded by the European Commission (EC), announced Mrs. Michelle Battye (GB) in a specialty session held yesterday.

The ERN unites 29 European healthcare providers in 11 EU member states in order to improve diagnoses and create more equitable access to high-quality treatment and care for patients with rare uro-rectogenital diseases as well as complex conditions needing highly specialised surgery. “This is a completely innovative step change in healthcare. It is not a project; it’s a new form of collaboration that Monday, 19 March 2018

will continue,” said Battye. Thirty million Europeans are affected by 6,000-8,000 rare diseases (‘rare’ being defined as fewer than 1:2,000 people) with many requiring surgical correction, some during the neonatal period or in childhood. Rare disease patients may need transitional or even life-long care provided by expert multidisciplinary teams (MDTs) in areas such as surgery, physiotherapy and psychotherapy.

When these patients cannot be adequately treated in their own country their case can be referred to an ERN to be dealt with using a new IT platform, the Clinical Patient Management System (CPMS).

Continued on Page 2... eUROGEN: Improving lives...

EUT Congress News

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Today’s ESU Courses ESU Course 41 Small renal masses: From concepts to tips and tricks in daily management 08.30-11.30 Orange Area, Room 4 ESU Course 42 Urological management of patients with neurological diseases 08.30-11.30 Orange Area, Room 5 ESU Course 44 Post-surgical urinary incontinence in males 12.00-14.00 Orange Area, Room 1 ESU Course 49 Prostate cancer update: How to optimise the everyday management of your patients 14.30-17.30 Orange Area, Room 7

ESU Course 52 How will immunotherapy change the multidisciplinary management of urothelial bladder cancer 15.30-17.30 Orange Area, Room 3 ESU Course 53 Robot renal surgery 14.30-17.30 Orange Area, Room 4

European Urology Today Editor-in-Chief Prof. M. Wirth, Dresden (DE) 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) Founding Editor Prof. F. Debruyne, Nijmegen (NL) Editing and Coordination J. Vega Onsite Reporting and Editing E. de Groot L. Keizer J. Tidman J. Vega X. Zheng

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No part of European Urology Today (EUT) may be reproduced without written permission from the Communication Office of the European Association of Urology (EAU). The comments of the reviewers are their own and not necessarily endorsed by the EAU or the Editorial Board. The EAU does not accept liability for the consequences of inaccurate statements or data. Despite of utmost care the EAU and their Communication Office cannot accept responsibility for errors or omissions.

By Erika de Groot Promising agents are awaited, particularly in immunotherapy for advanced kidney and bladder cancers while hormonal treatment still remains a major player in prostate cancer.

The unmet needs of urological cancer survivors were addressed today during the Specialty Session “EAU Patient Information Session”.

At the Game-Changing segment of Plenary Session 3, the key developments in the medical treatment of renal, urothelial and prostate cancers were taken up by Professors Marc-Oliver Grimm (DE), who discussed kidney and bladder therapies, and Nicolas Mottet (FR), who examined the promising options in prostate cancer.

In his presentation on prostate cancer (PCa), Chairman of Europa Uomo and cancer survivor, Mr. Ken Mastris (GB) stated that “We are asking the EU to help sustain awareness regarding PCa, provide the means to improve both diagnosis and treatment, and support equity of management for all.”

Prof. M.O. Grimm assesses advances in immunotherapy for renal and bladder cancer.

For urothelial cancer we have tremilimumab plus durvalumab/nivolumab plus ipilimumab… while adjuvant treatment is PD-1/PD-L1 plus combination,” he added.

Grimm also noted that ongoing game-changing trials in RCC in Phase 3 adjuvant setting include IMmotion Grimm discussed the outcomes of major studies such as KEYNOTE-045 which compared pembrolizumab with 010, CheckMate 914, and PROSPER RCC (neo-adjuvant), while in Phase 3 first-line metastatic RCC studies chemotherapy (paclitaxel + docetaxel + vinflunine) in platinum refractory disease (urothelial carcinoma) and include CheckMate 214. IMmotion 151, KEYNOTE-426, Javelin Renal 101, NCT02811861 and CheckMate 9ER. noted the increased gains in overall and progressionfree survival with pembrolizumab.

Mottet, meanwhile, provided an overview of androgen deprivation treatment of locally advanced prostate In advanced or metastatic urothelial cancer, Grimm cancer (PCa), issues in intermittent therapy, the role of also mentioned EMA approvals such as the antibody agent pembrolizumab in first-line therapy for cisplatin upfront aberaterone in M1 patients, and the standard ineligible patients and nivolumab and pembrolizumab of care (SOC) for newly diagnosed M1 disease. He said there is strong evidence for the recommendation to in second-line therapy after platin–based offer castration combined with chemotherapy chemotherapy. (docetaxel) to all patients whose first presentation is M1 disease and who are fit enough for docetaxel.

In RCC, Grimm mentioned CheckMate 214, which examined first-line nivolumab plus ipilimumab (nivo + Strong evidence also exists for offering castration combined with abiraterone acetate plus prednisone to ipi) versus sunitinib for treatment-naïve advanced or patients whose first presentation is M1 disease and metastatic RCC patients. For nivo + ipi the overall response rate was 42% compared to 27% for sunitinib, who are fit enough for the regime. with a progression-free survival of 11.6 months for nivo “Hormonal treatment remains a major player and a + ipi versus 8.4 months for sunitinib. key driver… however questions remain with regard to combination with salvage EBRT. And in M1 disease “Future directions indicate combination therapy with there is a revolution leading to improved survival,” he PD-1/PD-L1 inhibitors in RCC with nivolumab plus said. ipilimumab and PD1/PD-L1 inhibitors plus VEGFR-TKI.

A bladder cancer survivor himself, Mr. Andrew Winterbottom (GB) urged people to show support through six pledges. Of Pledge 1: Listen to us, he said “We as patients know a lot about the subject, too. We live it from symptoms, diagnosis, and treatment to aftercare. We can help you [urologists] gain additional insights.”

For Pledge 2: Talk about bladder cancer, he called for more open discussions about the fifth most common cancer in the world. Good quality, easily to read and easy to understand information that involves patients in its development was the core message of Pledge 3: Provide accessible patient information.

“It is not just about the treatment,” said Winterbottom about Pledge 4: Provide support which correlated with both Pledge 5: Campaign with us to disseminate vital information on bladder cancer and Pledge 6: Show us you care.

“Together we can make a difference.”

There is a lack of appropriate information and consistency for prostate cancer patients along their disease journey, according to qualitative study conducted in France, Germany and Spain.

The results were discussed by Dr. Patrick Cabri (BE) in his presentation “Prostate cancer: unmet needs of patients and their relatives (survey results)”. Cabri said, “There seems to be a need for information addressing key questions that patients (and their partners) have at each stage based on real-life situations.”

Better PCa detection with MRI, ultrasound

eUrogen: Improving lives...continued from Page 1

By Loek Keizer

Patients have had a huge part in making ERNs a reality and are involved in eUROGEN at every level, advising on strategy, disease specific areas, pathways, guidelines, and patient information.

Speaking at the session, Mrs. Serena Bartezzati (IT) from eUROGEN’s European Patients Advisory Group (ePAG) said, “I am a professional patient; I didn’t decide to be one, I am one.” She emphasized the role for patient groups in ERNs: “If you involve us we can really make the difference, as we can advise you what a disease means for patients.”

The case for MRI and further developments in ultrasound were made by Profs. Jelle Barentsz (NL) and Georg Salomon (DE) respectively. Salomon showed much improved experimental results at 29MHz rather than 9MHz. Barentsz, noting that an MRI helps clarify an ultrasound, hypothesised a combined MRI-Ultrasound: two short exams for the patient with a superior end result.

Advertising R. A. Matser L. Schreuder

patients a voice

By Joel Vega

For EAU18 Congress participants who wanted to know more about the imaging options for prostate cancer after Plenary Session 3, Thematic Session 4 followed up with more state-of-the-art lectures, case discussions and abstract presentations.

Communications and Promotion J. Bloemberg M. van Gurp I. Moerkerken

Disclaimer

Promising immunotherapy agents

Grimm examined the changes in medical treatment, including a few caveats in management that urologists need to know, and explored future directions such as combination and adjuvant treatments in renal cell carcinoma (RCC). He prefaced his talk with a brief look at targeting CTLA-4 and PD-1 pathways with monoclonal antibodies, and mentioned the development of approval of ipilimumab for melanoma that began in 2011 (in the USA and Europe).

ESU Course 50 Laparoscopic and robot-assisted laparoscopic radical cystectomy 14.30-17.30 Orange Area, Room 1

EUT Editorial Office PO Box 30016 6803 AA Arnhem The Netherlands T +31 (0)26 389 0680 communications@uroweb.org

Key advances in onco-urology Giving the

Mr. Rosario speaks on some of the drawbacks of the current implementation of multiparametric MRI.

MRI for diagnosis altogether and work on improving ultrasound. MRI can then be used for staging later down the line.”

“A third option is sticking with MRI. And if we do, we shouldn’t try to fit that in our current way of working Potential for ultrasound but develop new methods. If MRI identifies a lesion, The merits of (improved) ultrasound, when compared we need to be able to immediately biopsy. But that to multiparametric MRI and PET-CT, were of particular will have huge logistical and cost implications,” he interest in a clinical case discussion that was added. moderated by Prof. Alexander Govorov (RU).

3D Printing Mr. Derek Rosario (GB) spoke on some of the pitfalls At the same session, Prof. Ukimura (JP) gave a of MRI usage: “Evidence at the moment does seem to demonstration of some new 3D-printing techniques, favour multi-parametric MRI. Level 1A, 1B evidence including the use of an elastic material that simulates would suggest that MPMRI upfront aids in risk the consistency of prostate (and kidney) tissue. stratification and in the decision of whether or not to Although primarily a proof of concept, the imagingbiopsy. But it’s not perfect. Having an MRI done based 3D models with accurate representation of doesn’t easily fall into the current workflow of a tumours in transparent, elastic organs has led to practicing urologist, because you have to rely on a some careful conclusions. Ukimura: “Understanding third party. There is potential for loss in translation the exact location of the cancer is important to from acquisition, reporting, interpretation and then achieve negative surgical margins and functional implementation.” representation. By allowing surgeons to first practice on an exact replica of the patient’s prostate, they gain “We can continue working as we do now for a year or intraoperative precision and confidence before they go two, but there are two other options. We can forget into surgery.”

This allows virtual multi-disciplinary team meetings, so that the expertise travels across borders rather than the patient. The platform launched in November 2017 and eUROGEN already leads as its top user.

There is currently a lack of guidelines on rare urogenital diseases and eUROGEN aims to establish these even in areas where there is little or no evidence. At the session, Dr. Axel Bex (NL) from the EAU Guidelines Office explained that a new EAU initiative could help with this process. The Consensus Finding Development Committee (CONFIDENCE) receives requests for consensus meetings and assesses whether the areas are clinically relevant and/or highly controversial and whether the level of available evidence is low. If this is the case, steering committees are compiled, stakeholders selected, and consensus-finding questions are set and posed using a three-round Delphi survey, followed by a formal consensus group meeting with the stakeholders. As a result consensus statements on rare diseases and conditions can be published. eUROGEN will also collect currently lacking data on diagnosis, treatment, follow-up options, and long-term outcomes for the first time for rare disease patients at European level. In addition, the network will facilitate evidence-based research on new treatments and surgical techniques.

Monday, 19 March 2018

Underactive bladder: Management pitfalls Thematic Session 1 examines complex cases Congress news. . . . . . . . . . . . . . . . . . . . . . . . 1

By Joel Vega The optimal management of underactive bladder remains elusive and the wide variety of approaches taken by physicians were discussed yesterday in Thematic Session 1 which emphasised that the lack of a specific pathology has often led to underdiagnosis and ineffective treatments.

He also addressed the issue of whether UAB could be to detrusor underactivity (DUA) as overactive bladder (OAB) is to detrusor overactivity (DOA), as he noted that doing so would facilitate epidemiological studies, make the condition more understandable to patients, and prompt interest in research and drug development, among others. “But UAB symptom complex is desirable only if the diagnosis is sufficiently robust,” he said.

Chaired by Profs. Jean Nicolas Cornu (FR) and Salvador Arlandis (ES), issues such as defining underactive bladder (UAB) and the pathophysiological mechanisms were examined by speakers Mr. Nadir Osman (GB) and Dr. Tiago Antunes-Lopes (PT), respectively. Following the overview lectures, two cases were presented to look into the issue from various perspectives with Prof.

Gommert Van Koeveringe (BE) presenting the case of a man with Benign Prostatic Obstruction (BPO), and Prof. Andrea Tubaro that of a young woman with dysfunctional voiding problems.

In his closing remarks, Osman said DUA is a common problem in patients with LUTS seen in secondary care. He added that there is little published clinical or scientific research, and that defining a symptom complex of UAB is “...difficult due to the overlap in symptoms of DUA with other LUT dysfunctions.”

Antunes-Lopes, on the other hand, said there is a lack of original studies on the causes and mechanisms of UAB/DUA, as he underscored that the condition is agingrelated and multifactorial. “Aging, bladder outlet obstruction (BOO) and ischemia are putative causes of UAB/DUA. Contemporary views emphasise the importance of bladder afferent system,” he said.

Osman underscored the importance of properly defining UAB as he cited the ICS 2018 definition which says that UAB is “…characterised by a slow urinary stream hesitancy and straining to void, with or without a feeling of incomplete bladder emptying, Antunes-Lopes discusses the myriad of factors which can cause sometimes with storage symptoms.”

UAB

“We know that UAB is a clinical entity which requires more studies. For female patients it is essential to have a multidisciplinary treatment, and for men, TURP may not work and certainly proper assessment is necessary. In all cases, tailored treatment is recommended and exhaustive conservative management should first be considered ahead of new therapies,” said Cornu.

Congress highlights . . . . . . . . . . . . . . . . . . .2/3 Monitoring prostate cancer: Can we skip biopsies?. . . . . . . . . . . . . . . . . . . 4 Active Surveillance: What can a patient do?. . 6 Does new molecular subtyping in UC add to TNM?. . . . . . . . . . . . . . . . . . . . . . . . . . 7 Prevention of resistant bacterial infection. . . . 9 Complications of urethroplasty. . . . . . . . . . . 10 Stone treatment: What do we need for the future?. . . . . . . . . . . . . . . . . . . . . . . . . . . 11 Advanced BCa: Role of immune checkpoint inhibitors. . . . . . . . . . . . . . . . . . . . . . . . . . . 14 Sexual trauma of the male genital organs . . 15 Getting ready for penile transplants: A novel option?. . . . . . . . . . . . . . . . . . . . . . . 17 Bone metabolism and stones. . . . . . . . . . . . 18 Multi-tract PNL approach. . . . . . . . . . . . . . . 19 Reading and interpreting MRI . . . . . . . . . . . 20 EAUN Bladder Cancer Special Interest Group . . . . . . . . . . . . . . . . . . . . . . . 23

Award Gallery

First Prize Best Abstract by a Resident: F. Abdollah (Detroit, United States of America)

Second Prize Best Abstract by a Resident: D. Osses (Rotterdam, The Netherlands)

Third Prize Best Abstract by a Resident: S. Ernst (Homburg, Germany)

European Urology Resident’s Corner Award N. Sopko (Baltimore, United States of America)

ESUI Vision Award 2018 A. Alberts (Rotterdam, The Netherlands) Supported by INVIVO CORPORATION

ESTU René Küss Prize K. Decaestecker (Ghent, Belgium) Sponsored by GEBRO PHARMA + ROVI

ESTU Research Grant F. Regis (Suno, Italy) Sponsored by ORGAN RECOVERY SYSTEMS

EULIS Best paper for clinical research 2017 M. Cepeda (Valladolid, Spain)

Best paper published in 2017 by a YAU group G. Ploussard (France)

Best abstract presented by a Young Academic Urologist at EAU18 YAU Reviewer of the year A. Necchi (Milan, Italy) (represented by E. Xylinas (Italy)) G. Russo (Catania, Italy)

Best EUSP Clinical Scholar Award 2018, N. Grivas (Ioannina, Greece) Best EUSP Lab Scholar Awards 2018, J. Olivier, (Lille, France)

Monday, 19 March 2018

UROlympics Competition: 1st Prize Dr. Lee Chien Yap, 2nd Prize Dr. Guillaume Hugues, 3rd Prize Dr. Birzhan Ashkeyev Sponsored by COOK MEDICAL

EULIS Best paper for literature 2017 A. Pietropaolo (Italy)

The Expert-Guided Poster Tours attract many visitors! The last one will be held today at 12:15.

EUT Congress News

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Monitoring prostate cancer: Can we skip biopsies?

Scarce evidence to show prostate biopsy is not needed for active surveillance PCa patients Dr. Antti Rannikko Assistant Professor of Urology Department of Urology University of Helsinki and Helsinki University Hospital Helsinki (FI)

Currently, all guidelines recommend repeat biopsies for patients on active surveillance for low-risk prostate cancer. However, there is no consensus on when or how to take the biopsies. Nor is there enough evidence to support the notion that biopsies could be omitted altogether.

Prostate cancer (PC) active surveillance (AS) has become standard of care and is the recommended treatment option for low-risk PC. Initial risk stratification is mainly based on Gleason grading done on tissue samples traditionally obtained by transrectal systematic 12-core random prostate biopsies. If diagnostic biopsies show no worse than Gleason 6 (Grade Group 1) PC, AS is generally considered.

During the PSA era, more contemporary data from a randomized ProtecT trial is available. In this trial immediate curative treatment was compared with monitoring13. Monitoring was based on repeated PSA measurements only, while no routine follow-up biopsies were taken. Thus, ProtecT monitoring represents an intermediate between (pre-PSA era) watchful waiting and contemporary AS characterized by predefined follow-up biopsies and triggers for treatment. Despite the lack of follow-up biopsies, very low PC specific mortality was observed in the monitoring arm and there was no difference in PC specific survival between the treatment groups.

Interestingly, more men in the monitoring arm developed metastatic disease. However, to date, there is no detailed data published on whether this is explained by the fact that intermediate and even high-risk PC patients were also randomized and thus allocated into the monitoring arm.

Combined, these data would suggest that the role of routine follow-up biopsies in low-risk prostate cancer could be questioned.

Better initial risk stratification to reduce diagnostic misclassification A big leap forward would be to significantly decrease the rate of initial diagnostic misclassification, as it During AS, most guidelines recommend repeat may occur in even up to 60% of men considered biopsies as a key element of the surveillance protocol. eligible for AS3. Since the publication of Epstein These biopsies serve two purposes: 1. to detect criteria for clinically insignificant tumor, several reclassification due to initial diagnostic inaccuracy predictive tables and nomograms have been (misclassification, i.e. higher grade cancer missed at published to better predict the RP outcome14,15. diagnosis), 2. to detect reclassification due to true However, thus far, these have proven too inaccurate biological progression. with respect to decision on whether a man could avoid biopsies if put on AS. Besides common clinical Based on data from immediate radical prostatectomy variables included in the nomograms, such as PSA, series on patients eligible for AS, the rate of clinical T-stage, PSA-D, number of positive cores, also diagnostic misclassification has been estimated to be novel markers such as TMPRSS2-ERG, PTEN, 4K and around 32—58%1-3 while the rate of true biological Oncotype Dx have recently been studied in this progression has been estimated to be around 1-2% respect16-20. One of the most consistent markers predicting Gleason score upgrading at follow-up per year4,5. However, more reliable evaluation of the rate of true biological progression has become biopsies is PSA-D21,22. Regarding biomarkers, despite possible only recently, as exact serial rebiopsying of being promising, validation on external cohorts with the initial low grade lesions, as a function of time, can appropriate reporting typically required for diagnostic now be done owing to the emergence of the MRI-US studies is awaited. fusion biopsy technology.

Because of the high rate of diagnostic misclassification, a confirmatory biopsy is recommended. The purpose is to exclude higher grade cancer. If patient is still found eligible for AS after confirmatory biopsies, follow-up biopsies are recommended to detect true biological progression during AS. Consensus exists that confirmatory biopsies Trials suggest that serial MRI during AS may help in identifying patients at risk for progression should be taken within one year after diagnosis.

However, it is less clear when should the follow-up More recently, prostate MRI has received a lot of biopsies be taken and protocol recommendations vary attention as a potential tool to filter off men with from one to four years6. In addition, additional high-grade cancers otherwise considered suitable for triggers for rebiopsy have been used such as fast AS23-25. In PROMIS trial high sensitivity (93% vs 48%) rising PSA or change in DRE during follow-up. and negative predictive value (89% vs 74%) were observed for MRI versus TRUS biopsy in detecting Biopsies, however, are not without a problem. In the clinically significant cancer, albeit targeted fusion PRIAS trial, one in five men reported any form of biopsies were not taken but instead 5mm template complication7, sepsis being the most feared one. mapping biopsy was used as a reference26. In another Likely for this reason, it was found that compliance study, of 223 PRIAS eligible patients undergoing rate for repeat biopsies decreases gradually and is immediate RP, PIRADS-score was the only variable only 33% at 10 years after diagnosis8 while predicting Gleason upgrade in the final pathology in a compliance rate for PSA follow-up remains high multivariate model including common clinical variables (>90%). This finding was confirmed in SEER database (age, PSA-D, T-stage, number of positive cores)24. analysis showing that less than 13% of men underwent rebiopsy after two years9. Furthermore, in In an ongoing “pre MRI era” prospective randomized the PRIAS trial 4/5 biopsies taken during follow-up do trial, the SAMS trial, researchers are evaluating the not show reclassification and can thus be considered role of early “aggressive” diagnostics, i.e. whether redundant. Therefore, the question is, can we better extensive initial rebiopsy can be coupled with less identify patients at risk for progression and, thus, in intensive follow-up27. Interestingly, clinical factors and need for follow-up biopsy? Or perhaps, and even biomarkers have recently been combined with MRI. better, can we skip the biopsies for good?

PSA-D <0.15ng/ml2 and PIRADS-score 1-3 defined a cohort of men with no upgrading observed during Lessons from watchful waiting or “less active” follow-up biopsies25. Similarly, negative PCA3 and surveillance series negative MRI defined a cohort of men where clinically Before PSA era a typical PC diagnosis was an significant cancer was not observed28. incidental finding in TURP performed for obstructive urinary symptoms. These T1a/b cancers were often Surrogate markers for disease progression during considered “indolent” and no follow-up was surveillance exercised, thus, no follow-up biopsies were taken.

While intuitive, PSA kinetics has however proven a Despite the lack of any form of follow-up (and poor surrogate for disease progression. In the PRIAS biopsies), excellent long-term PC specific survival has trial, 46% of men undergoing RP for fast rising PSA been reported10-12. only (PSA-DT <3-years) were found to harbor Gleason 4

EUT Congress News

MRI-US fusion prostate biopsy

score 6 pT2 PC at RP. Thus, PSA-DT inaccurately classified men as harboring clinically significant disease. Similarly, in the Johns Hopkins AS cohort PSA-DT nor PSA velocity were significant predictors of progression at follow-up biopsy29. Literature is scarce on biomarkers during surveillance as surrogates for progression. A recent study looked at the role of 4K and found that it did not provide additive predictive value over base model during surveillance30. Also, the measured change in PCA3 over time was not associated with progression31.

Only a few studies have looked at the role of serial MRI during surveillance32-36. Besides being scarce, the published data suffers from lack of standardization and all published series are small, mainly retrospective and lack long term follow-up. Despite the weaknesses, all the trials suggest that serial MRI during AS may be helpful in identifying patients at risk for progression. Yet, the data does not support the notion that follow-up biopsies during prostate

cancer active surveillance can be omitted. Future randomized trials such as Precision and SPCG-17 will hopefully shed more light on the role of MRI at diagnosis and as a follow-up tool37,38.

Conclusion Despite recent progress in the field of biomarkers and especially prostate MRI imaging, there is little evidence in the literature currently to support the notion that prostate biopsies could be skipped on patients under active surveillance for prostate cancer.

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 Monday 19 March 10.30-12.00: Thematic Session 15, Active surveillance for low-risk prostate cancer

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Active Surveillance: What can a patient do?

Decision-making process in low-risk PCa requires active involvement of both clinicians and patients Riccardo Valdagni Assoc. Professor Department of Oncology and Hemato-oncology University of Milan Milan (IT)

Most of low-risk prostate cancer patients have the opportunity to choose among different radical approaches: radical prostatectomy, radiotherapy with or without hormonal therapy, brachytherapy with or without hormonal therapy.

In addition, many of them can also choose not to treat their cancer until (and if) it becomes necessary from a medical or personal point of view. In fact, Active Surveillance (AS) is currently considered a viable option by the international scientific community1,2.

AS implies a strict monitoring schedule of tests, examinations and biopsies with the aim of avoiding or delaying both overtreatment and the potential side effects caused by radical treatments3.

responsibilities. On the one hand, the clinician is the one who has the duty to properly inform the patient about the treatment options and about the risks and benefits of each option, as well as to empower him and provide practical tools for taking an informed decision. On the other hand, the patient has to take the lead and some responsibility in the decisionmaking process. Figure 1 provides a schematic diagram of the key roles and attitudes of patients and clinicians in the decision-making process.

Empowering the patient throughout this journey means, first of all, providing comprehensive and balanced information about the care process, about the therapeutic and observational options, and about all the relevant associated advantages and risks19.

Patients also need to play their part, by searching for and being open and receptive to this information.

Information is necessary, but it is not enough. Patients need to be engaged in the decision-making process.

To engage them and to improve informed valuesbased choices, clinicians should also take advantage from decision aid tools that provide explicit values clarification exercises, and patients should properly fill and use them.

It has been demonstrated that the adoption of decision aids results in higher levels of engagement In patients with low-risk prostate cancer, all these and lower decisional conflict related to feeling options, which are internationally accepted, have uninformed and uncertain about one’s values20. equally effective outcomes in the long-term4,5, but they Lower rates of people who remained undecided and significantly differ in terms of side effects. For example, higher rates of patients choosing an option congruent radical prostatectomy may induce urinary incontinence with their values have been also reported20. and erectile dysfunction, while radiotherapy may produce rectal urinary syndromes and erectile All this process implies a radical change in the dysfunction. With AS, finally, patients may experience doctor-patient relationship and in clinicians’ and anxiety and the burden of repeated biopsies. If we use patients’ attitudes when facing the decision-making travel as a metaphor for low-risk prostate cancer, we process, with reframed responsibilities. could say that given a precise starting point, there are multiple means of transportation that offer different The clinician, who is the subject matter expert on the travel experiences to reach the same goal: for the same disease, becomes the technical-medical expert on the state of disease, there are multiple therapeutic options possible options that can be offered to the patient. with different side effects, all able to reach the optimal The patient, who is the subject matter expert on his oncologic results. personal values, becomes the quality of life expert on choosing his option. Within this new relational frame, This scenario particularly challenges what we clinician’s responsibilities for a shared decisiontraditionally think of as the decision-making process making process are both technical-medical and in medicine: a linear path where the clinician supportive of patients’ quality of life; whereas prescribes the optimal strategy to the patient and patients have to take responsibility for a shared supports the patient in adhering to this prescription. decision and jump on the empowerment process promoted by the clinician.

For low-risk prostate cancer patients, the decisionmaking process necessarily becomes a situation Rebalanced responsibility where initially the clinician presents the patient with Adopting a multidisciplinary approach can foster this the possible strategies and then explains the related radical change towards a rebalanced responsibility side effects, supporting the patients in the decisionand a greater empowerment in the decision-making making process towards the “individual best journey of low-risk prostate cancer patients. The possible” option. presence of clinicians with different professional backgrounds may help create a common As a consequence, patients deal with the opportunity unambiguous language about the disease and its of choosing among multiple therapeutic/observational management options, which can facilitate information strategies that differ in terms of clinical and personal exchange with patients. A multidisciplinary setting costs and benefits. Such opportunity can be perceived may allow all the optimal options to be equally as a psychological burden by some patients and their presented within the same clinic18,21,22. families. Patients weight costs and benefits of every option in different ways. The counterintuitive option of Inter-specialist groups necessarily create a shared and fair dialogic context and prevent dyadic asymmetrical AS may increase the level of complexity of the decision-making process. Even if worldwide relationships21,23. In this inter-specialist group, the researches support the safety of AS6-9, patients may patient, but also his partner, is one of the specialized consider, above all initially, very unusual not to treat members, an expert on his life priorities and quality their cancer and “merely” monitor the disease. AS is of life. He necessarily becomes an active subject of a choice that implies a great deal of uncertainty for care, rather an organ to be cured. We could say that patients10,11. within a multidisciplinary setting, the need of patient empowerment in the treatment decision-making Increased responsibility process may be soundly accomplished.

The opportunity of choosing leads to an increased responsibility for patients and their loved ones. This To reiterate, the decision-making process for low-risk perceived responsibility for decision trade-offs is prostate cancer patients requires an active emotionally demanding. As a result, patients’ active involvement of both clinicians and patients towards a engagement in the decision-making process towards shared choice. Traditional doctor-patient power roles AS can be hindered12. What can a patient do? Patients and related functions and responsibilities need to be should gather scientifically sound information and challenged towards a greater partnership with evaluate these while keeping emotional focus as patients. Clinicians should take care of technicalmuch as possible. Just as it is for the clinician, the decision-making process for the patient is a combination of multiple factors that are linked not only by rational assumptions but also by emotional ingenuity. Clinicians have a key role in this process.

Indeed, different studies highlighted that the preference of the clinician has a strong influence in the decision-making process towards patients’ enrollment in AS13-18.

Decision-making process in low-risk prostate cancer is a journey where both the clinician and the patient are in the front seats, but with different roles and responsibilities

medical duties, but also support patients’ quality of life by promoting empowerment processes, while patients should take a greater responsibility and a leading role in their care process.

Fostering the creation and implementation of multidisciplinary settings may help tackle these challenges and support patient empowerment in the treatment decision-making process. We could conclude that there is a need to reframe the questions and instead of asking ourselves “What can a patient do?” or “What should clinicians do?”, a more valuable question could be “What should patients and clinicians do together?” to select the most effective way to reach a common goal, i.e. improving the patient’s health in its most comprehensive sense.

References 1. Mottet N, Bellmunt J, Bolla M, et al. EAU-ESTRO-SIOG Guidelines on Prostate Cancer. Part 1: Screening, Diagnosis, and Local Treatment with Curative Intent. Eur Urol. 2017;71(4):618-629. doi:10.1016/j.eururo.2016.08.003.

2. Aghazadeh MA, Frankel J, Belanger M, et al. NCCN Favorable Intermediate Risk Prostate Cancer Patients: Is Active Surveillance Appropriate? J Urol. 2017. doi:10.1016/j.juro.2017.12.049.

3. Klotz L. Active Surveillance for Localized Prostate Cancer a New Paradigm for Clinical Management. Springer; 2018. https://books.google.it/books?hl=it&lr=&id=Heg3D wAAQBAJ&oi=fnd&pg=PR5&dq=klotz+prostate+cancer&o ts=uSD4_k-LNa&sig=RkJzCTRjW4s6HpSW1ZHYfNEZ2qI#v= onepage&q=klotz prostate cancer&f=false. Accessed November 10, 2017.

4. Hamdy FC, Donovan JL, Lane JA, et al. 10-Year Outcomes after Monitoring, Surgery, or Radiotherapy for Localized Prostate Cancer. N Engl J Med. 2016;375(15):1415-1424. doi:10.1056/NEJMoa1606220.

5. Donovan JL, Hamdy FC, Lane JA, et al. Patient-Reported Outcomes after Monitoring, Surgery, or Radiotherapy for Prostate Cancer. N Engl J Med. 2016;375(15):1425-1437. doi:10.1056/NEJMoa1606221.

6. Marenghi C, Alvisi MF, Palorini F, et al. Eleven-year management of prostate cancer patients on active surveillance: What have we learned? Tumori. 2017;103(5). doi:10.5301/tj.5000649.

7. Bellardita L, Valdagni R, Van Den Bergh R, et al. How does active surveillance for prostate cancer affect quality of life? A systematic review. Eur Urol. 2015;67(4):637-645. doi:10.1016/j.eururo.2014.10.028.

8. Bul M, Zhu X, Valdagni R, et al. Active surveillance for low-risk prostate cancer worldwide: The PRIAS study.

Eur Urol. 2013;63(4):597-603. doi:10.1016/j. eururo.2012.11.005.

9. Bokhorst LP, Valdagni R, Rannikko A, et al. A Decade of

Following these premises, the decision-making process in low-risk prostate cancer becomes a journey where both the clinician and the patient are in the front seats, but with different roles and Figure 1: A schematic diagram of reframed doctor-patient roles in the decision-making process 6

EUT Congress News

Active Surveillance in the PRIAS Study: An Update and Evaluation of the Criteria Used to Recommend a Switch to Active Treatment. Eur Urol. 2016;70(6):954-960. doi:10.1016/j.eururo.2016.06.007.

10. Oliffe JL, Davison BJ, Pickles T, Mróz L. The SelfManagement of Uncertainty Among Men Undertaking Active Surveillance for Low-Risk Prostate Cancer. Qual Health Res. 2009;19(4):432-443. doi:10.1177/1049732309332692.

11. Parker PA, Davis JW, Latini DM, et al. Relationship between illness uncertainty, anxiety, fear of progression and quality of life in men with favourable-risk prostate cancer undergoing active surveillance. BJU Int. 2016;117(3):469-477. doi:10.1111/bju.13099.

12. Luce MF. Decision making as coping. Heal Psychol.

2005;24(4 SUPPL.). doi:10.1037/0278-6133.24.4.S23.

13. Van Den Bergh RCN, Essink-Bot ML, Roobol MJ, et al.

Anxiety and distress during active surveillance for early prostate cancer. Cancer. 2009;115(17):3868-3878. doi:10.1002/cncr.24446.

14. Bellardita L, Rancati T, Alvisi MF, et al. Predictors of health-related quality of life and adjustment to prostate cancer during active surveillance. Eur Urol. 2013;64(1):3036. doi:10.1016/j.eururo.2013.01.009.

15. Orom H, Homish DL, Homish GG, Underwood W. Quality of physician-patient relationships is associated with the influence of physician treatment recommendations among patients with prostate cancer who chose active surveillance. Urol Oncol Semin Orig Investig.

2014;32(4):396-402. doi:10.1016/j.urolonc.2013.09.018.

16. Zeliadt SB, Ramsey SD, Penson DF, et al. Why do men choose one treatment over another? A review of patient decision making for localized prostate cancer. Cancer.

2006;106(9):1865-1874. doi:10.1002/cncr.21822.

17. Gorin MA, Soloway CT, Eldefrawy A, Soloway MS. Factors that influence patient enrollment in active surveillance for low-risk prostate cancer. Urology. 2011;77(3):588-591. doi:10.1016/j.urology.2010.10.039.

18. Aizer AA, Paly JJ, Zietman AL, et al. Multidisciplinary care and pursuit of active surveillance in low-risk prostate cancer. J Clin Oncol. 2012;30(25):3071-3076. doi:10.1200/ JCO.2012.42.8466.

19. Pickles T, Ruether JD, Weir L, et al. Psychosocial barriers to active surveillance for the management of early prostate cancer and a strategy for increased acceptance.

BJU Int. 2007;100(3):544-551. doi:10.1111/j.1464-410X.2007.06981.x.

20. Stacey D, Légaré F, Lewis K, et al. Decision aids for people facing health treatment or screening decisions. Cochrane Database Syst Rev. 2017;2017(4). doi:10.1002/14651858.

CD001431.pub5.

21. Magnani T, Valdagni R, Salvioni R, et al. The 6-year attendance of a multidisciplinary prostate cancer clinic in Italy: Incidence of management changes. BJU Int. 2012;110(7):998-1003. doi:10.1111/j.1464-410X.2012.10970.x.

22. Valdagni R. Multidisciplinary Team Meetings in Cancer Care: We Could and Should do Better Than This. Clin Oncol. 2016;28(12):799-800. doi:10.1016/j. clon.2016.08.015.

23. Gomella LG, Lin J, Hoffman-Censits J, et al. Enhancing Prostate Cancer Care Through the Multidisciplinary Clinic Approach: A 15-Year Experience. J Oncol Pract.

2010;6(6):e5-e10. doi:10.1200/JOP.2010.000071.

Monday 19 March 10.30-12.00: Thematic Session 15, Active surveillance for low-risk prostate cancer

Monday, 19 March 2018

Does new molecular subtyping in UC add to TNM? Molecular tools will probably improve NMIBC understanding and treatment Eva Compérat Dept. of Pathology Hôpital Tenon, HUEP Sorbonne University Paris (FR)

Pathology is the gold standard for grading, staging and important for establishing treatment decisions in urothelial carcinomas (UC)1. Patients are treated according to the differentiation (grade) and the depth of invasion (stage) of their UC. The tumor/node/metastasis (TNM) staging system has been used for decades to help clinicians to classify carcinomas and to be a prognosticator, and also allows considering the management and including patients into clinical trials according to their stage.

Globally different patient groups should be distinguished in UC, although this model is probably too simple, especially with regard to the NMIBC (non-muscle invasive bladder cancer). A difference is made between NMIBC and MIBC (muscle invasive bladder cancer), the first group is treated in a conservative way, in the second exists the indication of neoadjuvant chemotherapy (NAT) and radical cystectomy2,3. Patients with metastatic disease should be treated with chemotherapy (CT)3. Major progress has been made on the molecular level and in the understanding of the bladder carcinogenesis. These findings should probably be integrated into the treatment strategies. At the moment no standard of which molecular findings should be integrated into staging and treatment exists. Therefore, still many treatment decisions rely on the classical pathology report.

Pathology From a pathological standpoint, patients can be divided into different groups: the NMIBC, MIBC and metastatic UC. Nevertheless, pTNM staging is not enough; several complementary factors have to be taken into consideration in each tumour, such as Cis (carcinome in situ), variant histology (VH) and lymphovascular invasion (LVI). Each of those items play a major role, but also other factors, where we pathologists need the urologist; for instance, size of the tumour and uni- or multifocality are important for the risk stratification1-3.

NMIBC The NMIBC group is the most heterogeneous and problematic. It includes poorly aggressive tumours such as pTa low-grade carcinomas and extends to high-grade pT1 invasive carcinomas; some of which can even invade the totality of the lamina propria, without growing into the detrusor muscle. The WHO 2016 has made a major step forwards in suggesting a sub-staging of pT1 carcinomas, having shown to have a major impact on the patient’s outcome1.

Nevertheless, no recommendation has been given on how to report; therefore it is the pathologist’s discretion to handle this issue1. In this group of UC, it is also important to take into consideration the above-mentioned items (Cis, LVI, VH), as already here they have a major impact on the patient’s outcome.

metastases and extracapsular disease which has shown to be an important prognostic factor6. Pathology also confirms distant metastasis, and adds information to the TNM system.

Molecular findings Since 2012, molecular studies have given a deeper insight on the landscape of UC, and the view on bladder cancer has fundamentally changed. Several authors7-10 described different molecular groups in UC, giving new detailed molecular classifications. In total four major classifications have been published since, the first preliminary studies divided UC into 3- 5 subtypes7-10.

These papers demonstrated that pathological findings did not always overlap with the molecular subtypes, although in some studies they partially did, especially in the NMIBC7.

An agreement exists that the main Molecular tumor types in UC and SCC molecular subtypes of UC are luminal and basal. Since the first publications, these classification systems have been changed with some details and samples, with different cut-offs for different have been developed further11. antibodies, according to each therapy , but it is not entirely clear which antibody is able to predict best Recent papers could demonstrate that gene the response of the ICI therapy. Some studies reported expression signatures could predict whether a patient therapeutic answers independently of PD-L1 would benefit from neoadjuvant therapy/platin expression on the tumour tissue14,15,16.

12-13 based- chemotherapy (NAT/CT) . The gene expression profile in some of these studies was Conclusion predictive of clinical outcomes. The basal subtype, Although in recent years much has been written and which is supposed to be close to squamous cell UC, discovered around metastatic UC, urologists should was associated with better survival, and more benefit not forget that the most frequent UC are NMIBC1. of NAT and the p53-like subtype, which belongs to the NMIBC represent more than 80% of UC. This luminal sub-group, was associated with bone heterogeneous group should probably be diagnosed metastases and chemo-resistant disease8,12,13. and stratified differently. pTNM is a good prognosticator; additional pathological findings like Another important treatment arm exists since 2014, grade, Cis, LVI and VH add a complementary value. which are the immune checkpoint inhibitors (ICI).

Molecular tools will probably be an improvement in Since Powles demonstrated a clear benefit in the NMIBC understanding and treatment. Ideally advanced metastatic disease, other studies could pathologists should be able to predict treatment confirm this finding14,15. Nevertheless, it is still not options, such as which patient should be given BCG 100% clear, based on which who should be given this therapy and who should have an early cystectomy. expensive medication, and whether pathology could play a role in this decision-making16.

With regards to MIBC and metastatic UC, pTNM still has an important role to play; probably the pN is underestimated and should be paid more attention, NMIBC Several important molecular findings are known in especially the reporting of extranodal spread of the tumour6. The long-term aim is to integrate molecular this group of UC. Alterations associated with lowgrade pTa tumors, such as HRAS mutations, FGFR-3 data, giving in the pathology report on the initial mutations and PIK3CA have been described; some are tumour tissue, either with the help of tissue markers or based on gene signatures—valuable information on known to be most of the time associated with good how to treat each patient in an optimal way. prognosis. On the other hand, we find completely different mutations in the high-grade tumors, such as TP53 mutations. FGRF3 mutations for example are There is increasing evidence that morphology and more or less absent in high-grade lesions18. Therefore, classical pathology (pTNM) alone will not be able to molecular stratifications are most welcome for better allow patients’ management in an optimal manner. understanding and management. Like in the MIBC, Molecular classifications can give an additional value basal- and luminal-like characteristics and different to the TNM staging and help refine the diagnosis. Both clinical outcomes exist19. A recent paper could show systems are complementary and have to be seen as a that mutations in well-known cancer driver genes powerful chance to improve patients’ management.

(TP53, ERBB2) were primarily found in high-risk tumours, together with APOBEC-related mutational References signatures. The authors suggest with an identification 1. Moch, H., Humphrey, P.A., Ulbright, T.M., Reuter, V.E. of subclasses to get a better prognosis and treatment WHO Classification of Tumours of the Urinary System and selection in this tumour group, which has a tendency Male Genital Organs. 4th Edition. World Health Organization: International Agency for Research on to recur1,19.

Cancer, Lyon, France, 2016.

MIBC As soon as the UC invades the detrusor muscle, the treatment strategy changes; NAT and surgery (cystectomy and lymphadenectomy) are recommended3. Pathology plays an important role, giving information about the depth of invasion, the lymph node status, VH if present, an association with Cis and describing LVI, but also the margin status after surgery must be taken into account. Final staging can only be done on radical cystectomy specimen. A clearly different outcome exists between the different categories (pT2a-4b)1. In case of NAT, down staging after surgery is common, but it is extremely important to tell the clinicians, whether UC components still remain in the cystectomy specimen4.

Metastatic disease Around 50% of patients who are treated surgically will develop metastatic disease5. The metastasis can be confirmed histologically by the pathologist.

Treatment strategies change once again in this group1,3; surgery is not indicated as a first approach.

The role of the pathologist is limited in this setting; it relies on giving information about lymph node Monday, 19 March 2018

MIBC 2. Babjuk M, Böhle A, Burger M, Capoun O, Cohen D, More molecular data are available for this group of Compérat EM, Hernández V, Kaasinen E, Palou J, Rouprêt UC7-11. Major impact papers could show that different M, van Rhijn BW, Shariat SF, Soukup V, Sylvester RJ, molecular groups should probably be treated Zigeuner R. EAU Guidelines on Non-Muscle-invasive differently12,13. With the help of genomic subtyping Urothelial Carcinoma of the Bladder: Update 2016. Eur Urol. 2017 Mar;71(3):447-461. classifier, different molecular consensus subgroups of MIBC can be predicted, showing that luminal tumours 3. Alfred Witjes J, Lebret T, Compérat EM, Cowan NC, De Santis M, Bruins HM, Hernández V, Espinós EL, Dunn J, had the best overall survival independently whether Rouanne M, Neuzillet Y, Veskimäe E, van der Heijden AG, NAT was given or not. On the other hand, basal UC Gakis G, Ribal MJ. Updated 2016 EAU Guidelines on had the most benefit in overall survival when given Muscle-invasive and Metastatic Bladder Cancer. Eur Urol.

NAT12,13.

Metastatic disease Several new findings, especially linked to the immune system and the mutational charge have enabled treatment of these patients in a different way, although there are still major open questions14,15,17.

Especially in the treatment with immune checkpoint inhibitors, the role of pathology is not 100% clear. It has been shown that UC expressing PD-L1 markers on a high level have a higher mutational charge, are of high-grade, display more relapses and have a shorter overall survival14. Some studies based their treatment on patients expressing PD-L1 on initial tumour

2017 Mar;71(3):462-475 4. Pokuri VK, Syed JR, Yang Z, Field EP, Cyriac S, Pili R, Levine EG, Azabdaftari G, Trump DL, Guru K, George S. Predictors of Complete Pathologic Response (pT0) to Neoadjuvant Chemotherapy in Muscle-invasive Bladder Carcinoma. Clin Genitourin Cancer. 2016 Feb;14(1):e59-65.

5. Goossens-Laan CA, Leliveld AM, Verhoeven RH, Kil PJ, de Bock GH, Hulshof MC, de Jong IJ, Coebergh JW. Effects of age and comorbidity on treatment and survival of patients with muscle-invasive bladder cancer. Int J Cancer. 2014 Aug 15;135(4):905-12 6. Fajkovic H, Cha EK, Jeldres C, Robinson BD, Rink M, Xylinas E, Chromecki TF, Breinl E, Svatek RS, Donner G,

Tagawa ST, Tilki D, Bastian PJ, Karakiewicz PI, Volkmer BG, Novara G, Joual A, Faison T, Sonpavde G, Daneshmand S, Lotan Y, Scherr DS, Shariat SF. Extranodal extension is a powerful prognostic factor in bladder cancer patients with lymph nodemetastasis. Eur Urol.

2013 Nov;64(5):837-45 7. Sjödahl G1, Lövgren K, Lauss M, Patschan O, Gudjonsson S, Chebil G, Aine M, Eriksson P, Månsson W, Lindgren D, Fernö M, Liedberg F, Höglund M. Toward a molecular pathologic classification of urothelial carcinoma. Am J Pathol. 2013 Sep;183(3):681-91.

8. Cancer Genome Atlas Research Network. Comprehensive molecular characterization of urothelial bladder carcinoma. Nature. 2014 Mar 20;507(7492):315-22.

9. Choi W, Porten S, Kim S, Willis D, Plimack ER, HoffmanCensits J, Roth B, Cheng T, Tran M, Lee IL, Melquist J, Bondaruk J, Majewski T, Zhang S, Pretzsch S, Baggerly K, Siefker-Radtke A, Czerniak B, Dinney CP, McConkey DJ. Identification of distinct basal and luminal subtypes of muscle-invasive bladder cancer with different sensitivities to frontline chemotherapy. Cancer Cell. 2014 Feb 10;25(2):152-65.

10. Damrauer JS1, Hoadley KA, Chism DD, Fan C, Tiganelli CJ, Wobker SE, Yeh JJ, Milowsky MI, Iyer G, Parker JS, Kim WY. Intrinsic subtypes of high-grade bladder cancer reflect the hallmarks of breast cancer biology. Proc Natl Acad Sci U S A. 2014 Feb 25;111(8):3110-5 11. Sjödahl G, Eriksson P, Liedberg F, Höglund M. Molecular classification of urothelial carcinoma: global mRNA classification versus tumour-cell phenotype classification.J Pathol. 2017 May;242(1):113-125.

12. McConkey DJ, Choi W, Shen Y, Lee IL, Porten S, Matin SF, Kamat AM, Corn P, Millikan RE, Dinney C, Czerniak B, Siefker-Radtke AO A Prognostic Gene Expression Signature in the Molecular Classification of Chemotherapy-naïve Urothelial Cancer is Predictive of Clinical Outcomes from Neoadjuvant Chemotherapy: A Phase 2 Trial of Dose-dense Methotrexate, Vinblastine, Doxorubicin, and Cisplatin with Bevacizumab in Urothelial Cancer. Eur Urol. 2016 May;69(5):855-62.

13. Seiler R, Ashab HAD, Erho N, van Rhijn BWG, Winters B, Douglas J, Van Kessel KE, Fransen van de Putte EE, Sommerlad M, Wang NQ, Choeurng V, Gibb EA, Palmer-Aronsten B, Lam LL, Buerki C, Davicioni E, Sjödahl G, Kardos J, Hoadley KA, Lerner SP, McConkey DJ, Choi W, Kim WY, Kiss B, Thalmann GN, Todenhöfer T, Crabb SJ, North S, Zwarthoff EC, Boormans JL, Wright J, Dall’Era M, van der Heijden MS, Black PC. Impact of Molecular Subtypes in Muscle-invasive Bladder Cancer on Predicting Response and Survival after Neoadjuvant Chemotherapy. Eur Urol. 2017 Oct;72(4):544-554.

14. Powles T, Eder JP, Fine GD, Braiteh FS, Loriot Y, Cruz C, Bellmunt J, Burris HA, Petrylak DP, Teng SL, Shen X, Boyd Z, Hegde PS, Chen DS, Vogelzang NJ. MPDL3280A (anti-PD-L1) treatment leads to clinical activity in metastatic bladder cancer. Nature. 2014 Nov 27;515(7528):558-62.

15. Bellmunt J, de Wit R, Vaughn DJ, Fradet Y, Lee JL, Fong L, Vogelzang NJ, Climent MA, Petrylak DP, Choueiri TK, Necchi A, Gerritsen W, Gurney H, Quinn DI, Culine S, Sternberg CN, Mai Y, Poehlein CH, Perini RF, Bajorin DF; KEYNOTE-045 InvestigatorsN Pembrolizumab as Second-Line Therapy for Advanced Urothelial Carcinoma.

N Engl J Med. 2017 Mar 16;376(11):1015-1026.

16. Sharma P, Retz M, Siefker-Radtke A, Baron A, Necchi A, Bedke J, Plimack ER, Vaena D, Grimm MO, Bracarda S, Arranz JÁ, Pal S, Ohyama C, Saci A, Qu X, Lambert A, Krishnan S, Azrilevich A, Galsky MD. Nivolumab in metastatic urothelial carcinoma after platinum therapy (CheckMate 275): a multicentre, single-arm, phase 2 trial.

Lancet Oncol. 2017 Mar;18(3):312-322.

17. Bellmunt J, Powles T, Vogelzang NJ; A review on the evolution of PD-1/PD-L1 immunotherapy for bladder cancer: The future is now. Cancer Treat Rev. 2017 Mar;54:58-67 18. Solomon JP, Lowenthal BM, Kader AK, Parsons JK, Flaig TW, Siefker-Radtke AO, Dyrskjøt L, Hansel DE Challenges in the Diagnosis of Urothelial Carcinoma Variants: Can Emerging Molecular Data Complement Pathology Review? Urology. 2017 Apr;102:7-16.

19. Hedegaard J, Lamy P, Nordentoft I, Algaba F, Høyer S, Ulhøi BP, Vang S, Reinert T, Hermann GG, Mogensen K, Thomsen MBH, Nielsen MM, Marquez M, Segersten U, Aine M, Höglund M, Birkenkamp-Demtröder K, Fristrup N, Borre M, Hartmann A, Stöhr R, Wach S, Keck B, Seitz AK, Nawroth R, Maurer T, Tulic C, Simic T, Junker K, Horstmann M, Harving N, Petersen AC, Calle ML, Steyerberg EW, Beukers W, van Kessel KEM, Jensen JB, Pedersen JS, Malmström PU, Malats N, Real FX, Zwarthoff EC, Ørntoft TF, Dyrskjøt L. Comprehensive Transcriptional Analysis of Early-Stage Urothelial Carcinoma. Cancer Cell. 2016 Jul 11;30(1):27-42.

Monday 19 March 08.00-10.30: Plenary Session 5, Precision Medicine

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Monday, 19 March 2018

Prevention of resistant bacterial infection Dr. Tommaso Cai Department of Urology Santa Chiara Regional Hospital Trento (IT)

• To reduce health care costs without adversely affecting the quality of care. In other words, limit inappropriate and excessive antibiotic use and improve and optimize therapy and clinical outcomes for the individual infected patient.

antimicrobial stewardship should be taken into account. A correct prescription of antibiotic is one of the most important components of antimicrobial stewardship and nine factors should be taken into account for selecting an antibiotic:

Antibiotic stewardship principles should be used in all health-related settings: prophylaxis, outpatients treatment, long-term care settings and hospitalized patients1.

tract infections (rUTIs)3. In everyday clinical practice, young women affected by rUTI show after antibiotic treatment asymptomatic periods associated sometimes with or without bacteriuria. Although it is not recommended, the majority of women with ABU is treated with poor results and occasionally a selection of multidrug-resistant bacteria can be observed.

1. Spectrum of coverage (use only drugs active against uropathogens) 2. Patterns of resistance (take into account your local pathogen resistance profiles) Recent studies demonstrated that ABU should not be treated in young women affected by rUTI, 3. Evidence or track record for the specified infection In everyday clinical practice, several aspects should be (perform regular audits with your staff) because it may play even a protective role in taken into account. In particular, the most important preventing symptomatic episodes, particularly 4. Achievable serum, tissue, or body fluid Co-Authors: F. M. Wagenlehner (DE), T. E. Bjerklund components of antimicrobial stewardship programs when Enterococcus faecalis has been isolated. concentration (e.g. urine) (obtain a useful biological Johansen (NO) are: Moreover, ABU treatment is associated with a sample to perform an accurate diagnosis) higher occurrence of antibiotic-resistant bacteria, 5. Allergy Antibiotics are among the most commonly prescribed • Regular training of staff in best use of antimicrobial agents; indicating that ABU treatment in women with rUTIs 6. Toxicity drugs used in human medicine. The prescription of • Adherence to local, national or international is even potentially dangerous3-4.

7. Formulation (Intravenous vs. per os); if per os, antibiotics is a very common practice in urological guidelines; assess bioavailability setting too. But it has been estimated that 50% are • Regular ward visits and consultation with Take home messages 8. Adherence/convenience (e.g. 2x/day vs. 6x/day) not needed or not optimally prescribed. infectious diseases physicians, with audit; • The therapeutic benefit of antibiotics should be (evaluate the patient’s compliance) • Treatment outcome evaluation; and balanced with their unintended adverse 9. Cost The continued misuse and overuse of antibiotics are • Monitoring and regular feedback to prescribers of consequences. paralleled by the growing frequency of multidrugtheir antimicrobial prescribing performance and Moreover, during antibiotic prescription, several other • Inappropriate antibiotic use is associated with resistant pathogenic strains. The evolution of resistant local pathogen resistance profiles. increased antibiotic resistance, adverse drug aspects should be taken into account and several pathogens has developed into a worldwide health effects and Clostridium difficile infection. “behaviours” should be avoided. Many patients crisis, with elevated health costs and greater risk of • Antibiotic stewardship is important for become colonized with potentially pathogenic poor patient outcomes. In hospital setting about 70% Adherence to guidelines The adherence to international guidelines, in preserving existing antibiotics and improving bacteria but are not infected, such as patients affected of bacterial infections are resistant to at least one particular for the use of antimicrobial prophylaxis, is patient outcomes. by asymptomatic bacteriuria or Foley catheter drug. On the other hand, the antibiotic drug pipeline another important component of antimicrobial • The adherence to international guidelines (EAU) colonization, or presence of WBCs not always is drying up. Very few new molecules are recently stewardship. Even if the use of antibiotic prophylaxis is able to reduce the costs of treatment and indicative of infection or the presence of fever due to introduced in urological armamentarium. Resistant before urologic surgical procedures is a recognised improve patients outcome. another reason, not the positive culture. Bacterial strains spread rapidly and one death every six strategy to prevent postoperative infections, its use • Antibiotic prescribing should be prudent, colonization is not an infection! A specific urological minutes in the world has been due to resistant should be risk-adjusted according to the procedure to setting in which we should improve antibiotic thoughtful and rational. bacterial infection. ensure that harms in terms of bacterial resistance in stewardship is the treatment of asymptomatic Easy and intuitive PDD in Precision an Modularity Flexibility S-Technologies Ergonomic Easy and intuitive PDD in Precision Modularity Flexibility individual and society do not outweigh the In other words, please stick to the European bacteriuria (ABU).

The clock is ticking… and this is the time to re-think S-Technologies Ergonomic Easy and intuitive PDD in Precision Modularity Flexibility S-Technologies Ergonomic Easy and intuitive PDD in Precisio benefits. In our recent paper we demonstrated that Association of Urology Guidelines on Urological our everyday clinical practice.

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TP 61 2.0 02/2018/A-E

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Monday, 19 March 2018

EUT Congress News

9

Complications of urethroplasty History-taking and adequate investigations are crucial in successful urethroplasties Dr. Sanjay Kulkarni Center for Reconstructive Urology And Kulkarni School of Urethral Surgery Pune (IN)

The management of urethral strictures is fairly standard in a high-volume center. But there are many controversies like transection versus non-transection of bulbar urethra, flaps vs grafts, dorsal vs ventral BMG, one stage vs two stage urethroplasty, etc.

Rectal injury The posterior urethra is usually displaced upwards and backwards towards the rectum.

Many patients have rectal injury and colostomy. In my experience, the safest way to protect the rectum is to place left index finger (non-dominant hand) in the rectum. It also gives me direction for further dissection. This complication has happened three times amongst more than 1000 cases operated in our unit. Two patients had a history of rectal injury with colostomy in the past, the small rent in the rectum was closed in layers (Figure 2). After bulbo membranous anastomosis I sutured the inferior wall of corpora spongiosa around the closed rectal rent as an additional layer. In the third patient I had to perform defunctioning colostomy with omental wrap between the rectum and urethra.

Pelvic fracture urethral defects are treated by anastomotic urethroplasty. Long anterior urethral strictures require augmentation with oral mucosa graft. The aim of this article is to highlight common complications and ways to avoid it.

Shortening of bulbar urethra I perform anastomotic urethroplasty mostly for traumatic bulbar strictures. The recurrence is uncommon but when it happens the stricture is obliterative, and requires redo anastomotic or augmented anastomotic urethroplasty. Repeated transections can lead to shortening of bulbar urethra.

Postoperative complications Bleeding Bleeding may occur from the perineum or from the site of oral graft harvesting. In the perineum usually it is the superficial perineal vessels, which cause bleeding, and hematoma. Figure of 8 stitches control bleeding from perineal vessels better than diathermy.

Twice in the last two decades I had to re-explore the patient for bleeding from the perineum. Very rarely, bleeding can take place from urethra. From the oral cavity, bleeding usually occurs from the raw area, a small artery from the buccinator muscle or from the edge of the wound.

Ours is a tertiary referral center for reconstructive urology. We get referrals from all over India and around the world. Since 1995, we have performed more than 4,061 urethroplasties including 1,157 anastomotic urethroplasties for pelvic fracture urethral defects. I was invited to demonstrate urethroplasties in more than 30 countries. This manuscript is based on the experience gained over the last three decades.

Preoperative In our center, we the urology team member perform RGU and MCU X rays under C arm control in the OR. During the study there may be intravasation (Figure 1) of the contrast in the veins or extravasation in the corpora spongiosa. Occasionally excess pressure during injection of the dye, bleeding may occur from the urethra, which usually is self-limiting.

Intraoperative complications Bleeding In cases of pelvic fracture urethral distraction defects urethroplasty bleeding can occur during various steps. Bleeding may occur form bulbourethral arteries after urethral transection. I control it by applying manual compression using gauze. The arteries go into spasm. Residual bleeding if any is controlled with figure of 8 sutures or diathermy, preferably bipolar.

During corporal separation, I may inadvertently incise the corpora cavernosa especially in redo urethroplasty. In this situation, I suture the corporotomy immediately with absorbable sutures.

The best way to avoid the complication is to consider that the two corpora are convex cylinders attached to each other in midline. I use sharp dissection with knife. I apply Allis tissue holding forceps and mastoid retractor (upside down) to give lateral traction on the corpora. I demonstrate the deep dorsal vein of the penis during corporal separation. I take the vein on one side of the midline. There may be tributaries which may bleed.

In case the vein comes in the way of pubectomy, I ligate it.

Figure 4: Perineal and scrotal hematoma seen in immediate post-operative period requiring exploration Figure 2: Finger inserted in rectum is seen in perineum (rectal injury) in a case of complex re do pelvic fracture urethral distraction defect

False passage Posterior urethra can be identified over a dilator, passed through the SPC tract. But this is a blind technique and rarely the dilator can come through a false passage through the bladder bypassing the posterior urethra. This can happen in case of HeyGroves bougie which has a fixed curvature.

Occasionally false passage exists due to previous endoscopic realignment and bulbar urethra (Figure 3) may be anastomosed to the false passage.

I use pediatric urethral dilators to insert through suprapubic tract in the posterior urethra. This pediatric dilators have a gentle curve and only at the tip. In long gaps I insert the left index finger to feel the tip of dilator at the apex of prostatic urethra. Alternatively, a rigid Mini Nephroscope can be passed in posterior urethra in case of high bladder. Using flexible cystoscope through the suprapubic cystostomy is the best method to identify the posterior urethra.

Risk of bulbar urethral necrosis In posterior urethroplasty, after transection of bulbar urethra, the blood flow is dependent on the retrograde flow from dorsal penile arteries and corporal arteries. In a butterfly fracture of pubic Lateral to the vein on either side are dorsal penile arteries. Injury to the dorsal penile arteries may cause rami, the corporal blood supply may be inadequate bleeding. More importantly, this would also affect the leading to vasculogenic ED. As discussed earlier, retrograde blood flow to the urethra. I bend the tip of improper corporal separation and inferior pubectomy can cause damage to dorsal penile diathermy and perform periosteal elevation using coagulation current. This lateralizes the dorsal penile arteries, leading to ischemia to bulbar urethra and bulbar urethral necrosis (Figure 4). arteries avoiding injury.

Foleys fallout The Foleys catheter may slip out after urethroplasty.

We have seen this with all Foley catheter brands. In such a situation I use two options. Best way is to perform urethroscopy with ureteroscope, insert guide wire through the urethra and then catheter over the guide wire. I have also used C Arm imaging for inserting guide wire and catheter (Figure 5).

EUT Congress News

Erectile and ejaculatory dysfunction in bulbar urethroplasty As per literature review, erectile dysfunction is seen in about 12% of patients of excision and primary anastomosis in bulbar urethroplasty. Few complain of cold glans. Due to the inherent risk of ED, I prefer augmentation urethroplasty in anterior urethra. I perform excision and anastomosis only in cases of obliterative bulbar trauma.

Patients may suffer from ejaculatory dysfunction and post-micturition dribbling. The bulbo spongiosus muscle dysfunction and urine accumulation in the nondependent bulbar urethra causes post micturition dribble. I prefer to perform one side dissection technique and muscle sparing as described by Kulkarni and Barbagli in 2009.This is known to have less ejaculatory dysfunction. Recent multicenter study

by Dimitry et al have evaluated PROMS showing advantage of one side dissection over conventional urethroplasty.

Chordee Temporary chordee is occasionally seen after penile and pan-urethral stricture repair. Rarely, it can be permanent. This is usually due to use of small grafts as compared to the length of stricture. I always keep the penis on stretch during pan-urethroplasty and I do not stretch the buccal grafts.

Abdominal complications Transpubic urethroplasty involves wrapping the anastomosis with Omental flap. Inadequate mobilization of omentum may act as a band and can cause nausea, vomiting and abdominal pain.

Wound infection The wound infection is rare after urethroplasty.

Surgical site infections manifest itself as redness, discharge of pus and fever. The abscess requires drainage under anesthesia. It recovers with antibiotics. Rarely I have seen leak of urine from the site of urethroplasty leading to infection and abscess formation.

I have seen osteitis of pubic bone after pubectomy leading to prolonged perineal and suprapubic pain.

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Complications of transpubic urethroplasty Total transpubic urethroplasty with Gigli saw is rarely used now. It leads to waddling gait and bladder hernia (Figure 6) is a known complication. I perform posterior pubectomy instead of total pubectomy.

Figure 5: Catheter inserted over a guidewire

Pain and numbness can occur in the perineum due to stretching of the perineal nerves during application of retractor. This neuropraxia pain may last longer.

Figure 1: Intravasation of contrast seen during retrograde urethrogram

In case the donor site was sutured, I open the sutures.

This helps in decreasing edema. In my series of more than 2,568 buccal graft urethroplasties, two patients had parotid duct injury. One patient had self-limiting partial injury which recovered over two weeks. A second patient required surgery to open a blocked duct.

Complications of flaps Fasciocutaneous flaps are occasionally used in urethral reconstruction; I use flaps only for ischemic strictures. I use pedicled preputial tube for bulbar urethral necrosis. I also see patients referred to me after failed hypospadias with use of pedicled flaps.

Complications after flap include hematoma, necrosis of the distal penile skin, torsion of penis and diverticulum formation. Today, grafts are most commonly used than flaps.

Pain Pain at the oral site of graft harvesting is usually temporary and recovers once the epithelium covers the raw area. Occasionally patients do get oral numbness and pain. I keep the donor site of buccal graft open.

Figure 3: Bulbar urethral stenosis due to ischemia to bulbar urethra in an operated case of pelvic fracture urethral distraction defect

near the second upper molar tooth. The duct can get injured during suturing of the donor site. Patient usually presents with pain and swelling in the region of affected parotid gland during mastication.

Parotid duct injury Parotid duct may get injured during harvesting of oral grafts. I always identify the duct opening which is

Figure 6: Distal penile skin necrosis after pedicled preputial tube urethroplasty

Rare complications Deep venous thrombosis, compartment syndrome and peroneal nerve injury are rarely published complications related to patient positioning in exaggerated lithotomy position. We use Lloyd Davies lithotomy position with sequential compression device for lower extremities. I have not seen this complication.

Monday 19 March 10.30-12.00: Thematic Session 18: Complications in external genitalia surgery

Monday, 19 March 2018

Stone treatment: What do we need for the future?

Future advances in instruments will allow faster stone clearance Prof. Olivier Traxer Sorbonne University - Medical School Tenon Hospital Paris (FR)

Dr. Etienne Xavier Keller Fellow in Endourology Tenon Hospital Paris (FR)

Dr. Vincent De Coninck Fellow in Endourology Tenon Hospital Paris (FR)

Surgical procedures for kidney stones are performed very frequently because of its high prevalence.

Due to technological advances of the surgical armamentarium, the use of flexible ureteroscopy (f-URS) has become widely adopted over the past years, when compared to percutaneous surgery and shock wave lithotripsy (Figure 1).

Since 2013, ureteroscopy is even considered as a first treatment option for all stones less than 20 mm following the guidelines of the European Association of Urology.

Extracorporeal shockwave lithotripsy Historically, the introduction of extracorporeal shockwave lithotripsy (ESWL) led to a revolution in stone management. While this treatment method stood the test of time, stone management gradually shifted towards an endoscopic approach.

Factors accounting for this trend in favor of f-URS are not well established, but certainly include the visual endoscopic control of stone fragmentation, the absence of stone density limitation, the possibility to treat patients irrespective of their body geometry, the ability to perform visual stone analysis and the combination of the intervention with a post-procedural double-J catheter insertion in order to prevent an eventual “Steinstrasse” phenomenon.

Newer generation lithotripters offer a facilitated stereotactic freehand ultrasound control and certainly can offer high degree of treatment success.

Combination of ureteroscopy and ESWL have been reported and may represent a future stone fragmentation approach1.

Miniaturization of endoscopes regarding anatomy Owing to technological advancements, there is an evolution towards miniaturization of ureteroscopes.

Since working channel diameter has not changed over the last years (3.6 Fr for all f-URS), scope miniaturization led to an overall outflow improvement

at a constant inflow. This has resulted in decreasing intrarenal pressure by still providing good irrigation flow. Further miniaturization of the urological armamentarium (e.g. ureteroscopes and accessory instruments) may further improve these parameters. As well, the rate of ureteroscopic insertion failure in the ureter will further decrease which will lead to higher single-session success rates.

The configuration of the working channel at the tip of the scope currently remains an unresolved problem. For treatment in a right-sided kidney, gravity will typically displace stones or stone fragments in a 3-o’clock position. This location is ideally accessible for accessory instruments inserted in f-URS with a working channel at about 3-o’clock (digital Karl Storz f-URS, fibre-optic Wolf Viper and Cobra, Boston Scientific LithoVue, Pusen). The opposite is valid for a left-sided kidney, where scopes with a working channel at about 9-o’clock offer a better access (fibre-optic Karl Storz f-URS, all Olympus f-URSs, digital Wolf Cobra vision and Boa vision). Implementation of the ability to rotate the working channel at the tip of the scope without vision nor deflection change would be a major future improvement.

adapted since it increases when increasing speed settings6. Further improvements are necessary to improve ureteroscopic handling.

Single-use ureteroscopes The introduction of single-use flexible ureteroscopes (suf-URS) certainly represents an important game changer of the current decade. Rather than a Miniaturization of ureteral access sheaths technological advancement, suf-URS have led to a With miniaturization of ureteroscopes, diameters of complete rethinking of the operative room logistics. ureteral access sheaths are decreasing as well. We generally use a ureteral access sheath with the smallest Indeed, suf-URS offer the advantages to be readily external diameter if the ureteroscope fits into the inner available, always sterile and without traces of lumen to decrease the risk of ureteral wall damage. The instrument wear such as deflection impairments. Also, downside of this miniaturization is that only small stone suf-URS do not require a dedicated sterilization process. Further, their implementation for treating fragments can be extracted. This may be overcome by locations that involve instrument forcing may cap the creating smaller stone fragments during lithotripsy by risks entailed by eventual instrument damages and using techniques like dusting or popcorning. repair costs of reusable scopes. In terms of quality, Alternatively, larger stone fragments can be entrapped at the tip of the ureteral access sheath and removed en some of the currently available suf-URS have visibility and maneuvering proprieties almost as good as bloc under endoscopic vision. contemporary digital reusable f-URS. Measure temperature Laser lithotripsy increases temperature of the irrigation The downside of this new instrument facility is the risk fluid and surrounding tissue in vicinity of the laser fibre of the appearance of low-cost suf-URS with low built quality on the market. Unexpected instrument tip, especially when working at high frequency and energy. This may happen in case of decreased irrigation deficiencies such as spontaneous loss of vision or deflection mechanism failure may become frequent when instruments are occupying the working channel and dangerous. Because of low instrument of the ureteroscope. This results in alternations of normal cellular functions and cell death2.To learn about replacement costs, surgeons may be tempted to force maneuvering and risk instrument breakage when temperature rising during lithotripsy, it would be facing a difficult access to a urinary cavity. Instrument interesting to measure intrapelvic temperature during failures may lead to disastrous complications, laser lithotripsy. eventually leading to open surgical extraction of a retained instrument. Therefore, it is of utmost Measure pressure The physiological intrapelvic pressure and the threshold importance to handle suf-URS with the same great for pyelovenous backflow are approximately 10 and 40 care for as reusable f-URS. Forcing suf-URS should only be done in expert hands. mmHg, respectively3.The pressure is the lowest during ureteroscopy in the distal ureter and the highest when operating in the renal pelvis4.Intrapelvic pressure rises 3D visualisation and image integration when irrigation pressure or hydrostatic column is The use of an iPad for kidney visualization was first raised. On the short-term, this may result in fornix presented for percutaneous access to the pyelocaliceal rupture and renal extravasation that may cause system in 20137.Further developments towards complications like bleeding and sepsis. It may also augmented reality, 3D endorenal vision and live cause focal parenchymal scarring due to degeneration stereoscopic extracorporeal imaging of intrarenal stone of renal tubules on the long-term5.To prevent these burden are to be expected and may facilitate navigation complications, it would be interesting for future and further improve stone clearance in the near future. developments to integrate a pressure control system to the ureteral access sheath or ureteroscope.

Laser generators and settings Currently available Ho:YAG generators combine up to Robotics four laser cavities, allowing for pulsed firing In the year 2012, a robotic system has been introduced frequencies up to 80 Hz, with or without Mosesfor retrograde intrarenal surgery. By sitting at a capacity. Although such improvements may enhance console, the surgeon is able to deflect, rotate, advance stone fragmentation, a more trivial limitation remains and retract the ureteroscope by using two joysticks or a unsolved: endoscopic visibility impairment due to small central wheel. With touch screen buttons and foot floating fragments (“dust”). The latter limitation can pedals, the operator can also change the speed of only be overcome by improving irrigation outflow, movements and can advance, retract and activate the which will probably parallel further future laser fibre. Initial results are acceptable in terms of miniaturization of scopes. stone-free rate, ergonomics and decreased radiation exposure. However, irrigation flow regulation is less We currently recommend to use low energy settings (e.g. 0.2 J up to 0.8 J) to limit the risk of eventual firing on tissue, with a stepwise frequency increase (typically up to 10-15 Hz) to reach an acceptable visibility for secure stone fragmentation. Consequently, we currently do not see any advantage of high power laser generator capabilities for lithotripsy and rather question whether other energy sources can be used for stone fragmentation.

Figure 1: Evolution of urolithiasis treatment over 30 years in Tenon hospital, Paris, France

Monday, 19 March 2018

Figure 2: Faster stone clearance at low intrarenal pressure

Rethinking definitions: Stone free rate, fragments and dust Whatever laser settings are used, Ho:YAG lithotripsy will produce a mixture of small fragments with floating capacity (commonly called “dust”) and of more sizable fragments. The latter may eventually be accessible to basket retrieval and allow stone analysis, while the so-called dust seems to evacuate spontaneously within less than a week. Most authors agree that fragments

<2-3 mm are considered to pass spontaneously an undamaged ureter.

Nevertheless, the natural history of such fragments is unclear and it is conceivable that de novo crystallisation may appear on the basis of small stone fragments retained in the kidney. This is typically found after ESWL with a risk of stone recurrence8.Therefore, the definition of a stone-free status may be challenged in future studies and tiny fragment residuals shall be documented whenever present in follow-up imaging.

Evacuation of stone fragments To achieve endoscopic stone-free status, it would be interesting for future developments to integrate active suction facility for ureteroscopy, leading to low intrarenal pressures and sustained efflux of stone fragmentation products.

Double-J catheter tolerance Many efforts have been put to reduce double-J catheter morbidity, but neither geometry, length, material proprieties, nor catheter coating variations have been successful. Novelties such as the suture-like ending J-Fil catheter may overcome this long-lasting burden9.

Stone disease: Symptom of another disease Awareness among urologists and primary health care givers is high about erectile dysfunction as symptom of an increased risk of coronary heart disease10.This is not valid for stone disease, even though the relationship has been established11.In fact, stone disease is the symptom of a myriad of public health threats. In a majority of patients, pathophysiology of stone disease is linked to the same nutritional habits that may lead to metabolic syndrome.

Moreover, hypercalciuria may be linked to wider metabolic imbalances resulting in osteoporosis, if not readily recognized. It is therefore of utmost importance to perform a metabolic evaluation of every stone former, irrespective of their age or number of stone episodes. The awareness about this threat among urologists and primary health care givers is low and has to increase in the years to come.

Patient experience during their hospital journey Lately, patient experience and health outcome has become a high priority in health care12.In the near future, reimbursement of treatments may become linked to care giver’s performance as measured by patient’s experience metrics. “Sufficient information given about treatment” and “sufficient explanation of risks and benefits of surgery” were significantly associated with a high patient’s satisfaction score in a recent study on emergency abdominal surgery13.

Informative procedural brochures and videos are the basis for a well-informed consent.

Faster stone clearance In the years to come, development of instruments and accessory devices for endoscopic stone treatment would allow faster stone clearance, while ensuring low intrarenal pressure (Figure 2). Multimodal integration of enhanced endoscopic vision, live extracorporeal imaging of the pyelocaliceal system, pressure and temperature control and tensile force feedback may improve navigation, possibly allowing for more rapid and safer endoscopic procedures.

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 Tuesday 20 March 08.00-13.30: Plenary Session 7, Stones

EUT Congress News

11

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 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.

12

padeliporfin4 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

EUT Congress News

www.stebabiotech.com | Info@stebabiotech.com

Monday, 19 March 2018

URO 84 2.0 02/2018/A-E

As Every Detail Counts â&#x20AC;&#x201C; Visibly higher resolution with the new flexible uretero-renoscopes FLEX-XC and FLEX-X2S

KARL STORZ SE & Co. KG, Dr.-Karl-Storz-StraĂ&#x;e 34, 78532 Tuttlingen/Germany, www.karlstorz.com

28 - 31 August

UROLOGY CLEARLY DEFINED

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

Chairman

Scientific Co-Chair

Co-Chairman

Scientific Co-Chair

*

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Get your bottle opener key chain at our booth D58 and discover our Clearly Defined Urology Solutions.

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

Monday, 19 March 2018

EUT Congress News

13

Advanced BCa: Role of immune checkpoint inhibitors ESU Course 52 shows immunotherapy’s impact on MDT management of urothelial bladder cancer Dr. Andrea Necchi Department of Medical Oncology Fondazione IRCCS Istituto Nazionale dei Tumori Milan (IT)

Bladder cancer (BC) is the most frequent among urothelial carcinomas (UC) that also include the less common UC arising from renal pelvis, ureters and urethra. It is the ninth most common cancer in the world, the sixth most common cancer in the United States and the second most common genitourinary tumor. It is a major cause of morbidity and mortality worldwide, causing approximately 429,000 new cases resulting in 165,000 deaths annually.

An estimated 79,030 new cases of urinary bladder cancer (60,490 men and 18,540 women) were diagnosed in the United States in 2017 with approximately 16,870 deaths (12,240 men and 4,630 women) during this same period. Approximately, three times more men than women are diagnosed with bladder cancer; the majority of patients are > 65 years old. Approximately 4% of the patients have metastatic disease at the time of diagnosis.

Additionally, about half of all patients relapse after cystectomy depending on the pathologic stage of the tumor and nodal status. Local recurrences account for about 10% to 30% of relapse, whereas distant metastases are more common.

Despite improvements in clinical, surgical and medical management of locally advanced or metastatic UC, little progress was made over the past decades and outcomes unfortunately remained almost unchanged. Yet UC is considered a chemosensitive disease and systemic platinum-based combination chemotherapy is the standard of care in the neoadjuvant, adjuvant and first-line therapy settings. Responses to cisplatin-based first-line chemotherapy are reasonable, however a majority of patients ultimately progress and the optimal subsequent systemic treatment remains unsettled.

Second-line agents demonstrated only limited activity and yield objective response rates (ORR) of 5-20%. In the most updated trial-level meta-analysis, the median “median” overall survival (OS) was 6.9 months. Of note, standard chemotherapy for UC often causes hematologic and non-hematologic side effects with severe toxicities even with the use of noncisplatin based chemotherapy in first-line.

a first-line treatment for patients with locally advanced or metastatic urothelial carcinoma who are not eligible for cisplatin-based chemotherapy.

More recently, based on tumor response rate and duration of response, FDA also granted accelerated approval to two newer PD-L1 inhibitors, avelumab and durvalumab for patients with locally advanced or metastatic urothelial carcinoma whose disease progressed during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant platinum-containing chemotherapy.

Renewed options for maintenance therapy after first-line Given that most patients respond to first-line chemotherapy but the duration of response is usually poor, an attractive approach is to introduce maintenance therapy after first-line treatment for preventing or delaying the progression of disease, preventing deterioration of tumor-related symptoms and prolonging survival. With regard to maintenance therapy, a few agents have been investigated in UC. Double-blind phase 2 trials had randomized patients to receive sunitinb or placebo and lapatinib or placebo, respectively; both these trials failed to demonstrate any statistically significant improvement in OS in the experimental arm.

Additionally, two phase 2 trials with vinflunine were conducted in this setting. The Spanish “Maja” trial was a phase 2 randomized trial that evaluated maintenance vinflunine compared to best supportive care (BSC). In this study, 88 patients were assigned to receive vinflunine (n=45) or BSC (n=43). For the first time in UC, vinflunine improved PFS with an hazard ratio (HR) of 0.59 (95%CI: 0.37-0.96, p=0.031).

However OS data were still immature at the time of the analysis and are warranted prior to set a role for vinflunine in this context. Results from the second vinflunine study, i.e., the “Jasima” trial, have been presented only in a very preliminary stage and no conclusion could be drawn.

Recent studies have investigated the role of ICI as maintenance in patients who experience at least a stable disease (SD) to first-line chemotherapy. An ongoing, randomized, phase 3 trial (Javelin Bladder-100, NCT02603432), is evaluating avelumab, an anti-PD-L1 antibody, plus BSC versus BSC alone, being OS the primary endpoint in a study that is expected to enroll 668 patients. The results of this trial will be the first presented with an immunotherapy approach in this context.

Future prospects: Emerging challenges with the use of ICI in UC and biomarker data In the salvage therapy of metastatic UC, combination immunotherapy may result in augmented ORR and In the first-line setting, the selection of the enhanced survival benefit compared to single-agent chemotherapy regimen partially depends on the ICI. The early results with double regimen use (i.e., presence or absence of medical comorbidities, such us anti-PD-1/PD-L1 plus anti-CTLA4) or even the triple cardiac disease and renal dysfunction, along with the regimen (by adding cabazitaxel) seem to follow this risk classification of the patient based on disease path, although toxicity and sustainability of such extent. In general, long-term survival with combination combinations will be hard. Additionally, several chemotherapy alone has been reported only in uncertainties still lie regarding the optimal use of ICI. good-risk patients, defined as those with good As an example, the optimal duration of treatment for performance status, no visceral (i.e. liver, lung) or bone responders, as well as the optimal interruption of disease, and normal alkaline phosphatase or lactic treatment for progressors, are currently debated. In a dehydrogenase levels. Poor-risk patients, defined as post-hoc analysis of IMvigor210 study, approximately those with poor performance status or visceral disease, 5% delayed responses were observed after the first have consistently shown very poor tolerance to evidence of PD, denoting a disease-modifying activity multi-agent combination programs and few complete induced by immunotherapy that is still largely remissions, which are prerequisite for cure. unaccounted for.

Similar trends were seen regarding OS, as median OS was 12.3 months (95%CI: 6.0-not estimable [NE]) for IC2/3+ patients and 19.1 months (95%CI: 9.8-NE) for IC0/1+ patients.

Keynote-052 study evaluated pembrolizumab in 370 patients in the same setting. In this study, like in all pembrolizumab studies in UC, PD-L1 expression was assessed using Dako antibody clone 22C3, and the combined positivity score (CPS) was developed. This score evaluated the number of PD-L1 staining cells (tumor cells and IC) out of the total number of viable tumor cells. Using Receiver Operating Characteristic (ROC) curve analysis along with the ORR and biomarker prevalence profile, the CPS cut-off of 10% was determined to be the optimal enrichment cut-off for predicting response.

At the time of the last update, the ORR in all comers was 29% (95%CI: 25-34%), in CPS>10% population was 37% in the training set, and 51% in the validation set, showing some enrichment. Data on OS was not yet given. Interestingly, appreciable number of additional responses were captured using an 18 T-cell inflamed gene expression Treatment of solid cancers has been revolutionized by the revival of various panel as compared to the PD-L1 immunotherapeutic strategies, particularly recognizing the importance of T-cell immunohistochemical biomarker inhibitory pathways and immune checkpoints inhibitors (ICI) (Photo: MediPaper) alone.

In summary, there is currently no evidence supporting the PD-L1 use as a biomarker for selecting patients for ICI therapy in chemotherapynaive patients, and definitive conclusions will be likely drawn with the results of the ongoing, randomized, phase 3 studies that are currently open in the first-line setting (NCT02853305, NCT02807636, NCT02516241, NCT03036098).

Regarding cohort 2 of IMvigor210 study, in contrast with the results obtained in the cohort 1 of the same trial, patients with higher expression of PD-L1 (i.e., IC 2/3+) had better ORR (26%) than the ones with no or weak expression (IC 0/1+). Similar trend was observed for OS, as median OS in IC2/3+ population was 11.4 months (95%CI: 9.0-NE) versus 6.5 months (95%CI: 4.4-8.3) for IC0 patients. Most noteworthy, several additional data were obtained that may be used for patient enrichment pending validation. These results included the association between the T-effector (Teff) gene signature (i.e., expression of CD8, granzymes, perforin, cytokines and other factors) and PD-L1 IC status, as well as between the expression of multiple immune inhibitory regulators (e.g., LAG3, HAVCR2, CTLA4, IDO1, FOXP3, CD244) and PD-L1 status.

Furthermore, two key factors were associated with atezolizumab response: Teff gene signature, and Cancer Genome Atlas (TCGA) luminal II subtype (p=0.0072). Luminal-I tumors displayed low Teff expression, and may be regarded to as being characterized by an “immune desert” in their microenvironment, according to Rosenberg et al.

Interestingly, this subtype is also enriched of alterations of the fibroblast growth-factor receptors (FGFR) genes, and therefore combination of ICI and The treatment of various solid cancers has been pan-FGFR inhibitors might be particularily beneficial Response to chemotherapy after ICI will represent revolutionized by the revival of various for their patients. Finally, tumor mutation burden another future challenge, and the optimal immunotherapeutic strategies, particularly (TMB), evaluated by means of quartile split and using chemoimmunotherapy sequence will require the recognizing the importance of T-cell inhibitory the FoundationOne test, was significantly associated conclusion of the ongoing phase 3 trials in the pathways, heralded by the immune checkpoints first-line. Finally, the search for the optimal biomarker with response and survival to atezolizumab in these inhibitors (ICI). patients. Confirmatory results may come from the approach will necessarily require harmonisation and translational body of evidences from concluded phase new research, and it is possible that renewed PD-1 and PD-L1 checkpoint inhibitors have garnered 3 IMvigor211 trial, which compared atezolizumab with perspectives may come from academia and attention based on clinical trial data. standard of care in the same clinical setting. Based on pharmaceutical company intersect. the results available to date, PD-L1 expression was The PD-L1 inhibitor atezolizumab and the PD-1 associated with improved OS in both arms: in the In the first-line metastatic setting, biomarker results inhibitor nivolumab received accelerated approval for have been disclosed for atezolizumab and atezolizumab arm, median OS was 8.6 months in ITT the treatment of patients with locally advanced or population versus 11.1 months in IC2/3+ patients. pembrolizumab in patients who are ineligible to metastatic UC who have disease progression during receive cisplatin-based chemotherapy. or following platinum-containing chemotherapy or Keynote-045 study was a phase 3 study which In IMvigor210 cohort 1 study, PD-L1 expression was within 12 months of neoadjuvant or adjuvant compared pembrolizumab with standard evaluated in immune cells (IC) using the Ventana treatment with platinum-containing chemotherapy, chemotherapy. In this study, 542 patients were antibody clone SP142. Cut-off definitions were the regardless of PD-L1 expression level. Recently, also the following: PD-L1 IC2+/3+ if ≥5% positive IC, or 1+ if randomized to receive pembrolizumab 200 mg IV PD-1 inhibitor pembrolizumab reported positive OS every three weeks for maximum two years versus 1-5% positive IC. Disappointingly, in this cohort 1 data versus standard of care chemotherapy in this there was no enrichment in response according to the three-weekly docetaxel, paclitaxel, or vinflunine. In indication. In addition, atezolizumab and this study, in contrast with IMvigor211 findings, PD-L1 expression of PD-L1, as the ORR was 28% (95%CI: pembrolizumab also received accelerated approval as 14-47%) in IC2/3+ and 21% in IC-negative patients. expression was a negative prognostic factor in both 14

EUT Congress News

pembrolizumab and chemotherapy arm: the median OS for pembrolizumab was 10.3 months in ITT population versus 8.0 months in CPS≥10%.

For both durvalumab and avelumab, despite signals of improved responses were reported in PD-L1 positive patients (using Ventana SP263 antibody and Dako 73-10 antibody, respectively, and both evaluating tumor cells and immune cells), conditional approval was granted for all comers regardless of PD-L1 expression.

Finally, translational findings from the nivolumab phase 2 CheckMate275 study have been reported. In this study, the ORR was 19.6% in all comers, and a trend toward enriched responses in PD-L1-positive patients was found (5% cutoff on tumor cells only; Dako antibody, clone 28-8). Of note, TMB showed a statistically significant positive association with ORR and PFS, and a strong association with OS, even when adjusted for baseline factors and tumor PD-L1 expression.

Latest data on resistance biomarkers of immunotherapy in UC Fibroblast growth-factor receptor (FGFR) expression is associated with a non-T-cell-inflamed tumor microenvironment. Emerging data point to the potential of poorer response to anti-PD-(L)1 therapy in FGFR aberration-positive patients.

A recent update of the “The Cancer Genome Atlas” (TCGA) bladder cancer consortium reported that 44% of luminal-papillary (luminal 1) tumors have evidence of FGFR3 alterations, and remain immunologically “cold” as compared to the other subtypes. Therefore, there appears to be unique biology in UC which may affect response to immunotherapy, with an FGFR3 altered luminal 1 tumor predicted to have a lower likelihood of benefit from immune modulating therapies. These data link FGFR alterations with the urothelial carcinoma population least likely to respond to checkpoint inhibitors. This also represents the framework for testing the combination of agents targeting FGFR-altered tumors, either alone or combined with ICI. The aim of these studies is to explore if compounds inhibiting FGFR are able to induce a T-cell-inflamed phenotype, restoring sensitivity to PD-L1 inhibitors and improving their efficacy in urothelial carcinoma.

Monday 19 March 15.30-17.30: ESU Course 52, How will immunotherapy change the multidisciplinary management of urothelial bladder cancer?

Monday, 19 March 2018

Sexual trauma of the male genital organs Thematic Session 18: Complications in external genitalia surgery Dr. Marcel Fiedler Consultant Urologist Department of Urology SLK-Kliniken Heilbronn Heilbronn (DE)

wooden objects are hard to catch endoscopically because they drift in the dome of the bladder. In all cases, the bladder has to be inspected carefully for bladder wall injuries. Small extraperitoneal injuries can be treated conservatively with a catheter for a minimum of one week and cystography before catheter removal. Intraperitoneal or big extraperitoneal bladder wall injuries have to be treated with open surgery immediately.

If an object cannot be removed from the bladder endoscopically, a sectio alta is the treatment of choice.

Traumatic bladder ruptures due to sexual intercourse are very rare and might only occur in patients performing hardcore sexual acts with a very full bladder, mostly after intake of a larger quantity of alcohol. The treatment required is open surgery.

In some, rare cases, sexual activity can lead to dangerous results. Sexual trauma is more frequent in men (54 %) than in women. It can happen during heterosexual, homosexual or auto-erotic sexual practices. In many cases, sexual trauma causes intense sense of shame which delays the presentation to a physician. This delay may aggravate the negative Penile trauma effects of the trauma itself. a) Rupture of the frenulum and paraphimosis Rupture of the penile frenulum during sexual Reviewed from statistical side, infectious complications intercourse represents the most frequent sexual of sexual activity (such as urinary tract infections or trauma in daily urological practice. A short sexual transmitted diseases) are much more frequent frenulum combined with the mechanical stress of than sexual trauma. However, the psychological strain intercourse to the tip of the penis and to the for the person concerned is high after sexual trauma foreskin leads to a rupture and bleeding which is and the variety of mechanisms that can lead to sexual of course not life-threatening, but causes a lot of trauma and the variance of complications caused by it psychological strain for many patients and their are demanding for the urologist. partners.

The purpose of this review is to present and categorize sexual trauma and propose ways to solve the problems caused by them.

Trauma of urethra and bladder Most traumas of the urethra are caused by auto-erotic practices. Different foreign bodies are inserted into the meatus of the urethra to archieve sexual stimulation. This can lead to direct perforation of the urethra, mostly in the navicular fossa or the bulbar part. In most cases, this problem can be solved by removal of the foreign body. Endoscopic removal might be challenging: Parts of a chemical test glass broken within the urethra are for example difficult to grab using endosopic graspers.

Urethrocystoscopy has to be performed in every case to be sure that all foreign bodies have been removed and to document the extent of the injury. Afterwards, in most cases placement of a transurethral catheter is mandatory. This may be done over a guide wire placed during cystoscopy to prevent an aggravation of the trauma during insertion of the catheter. Catheter time depends on the severity of the trauma. During catheter removal, a urethrogram can be performed to document complete healing of the urethral injury.

Only in rare cases with severe injury, an open surgical revision of the urethra is needed, for example in cases with urethral fistulas. If the foreign body cannot be removed endoscopically, for example, because a knot in an electrical cable is stuck in the urethra, open surgery is also necessary.

Direct rupture of the male urethra during sexual intercourse is rare – and may also be worked up with urethrography and urethrocystoscopy. Treatment is done conservatively with an catheter placed over a guide wire or surgically depending on the extent of the trauma. Direct trauma to the female urethra during sexual intercourse is very infrequent. However, dilatation of the female urethra due to an insertion of the erected penis has been documented in cases of vaginal atrophy or agenesis. This can lead to pain and even stress incontinence.

Most patients are young with a history of untreated frenulum breve or phimosis before their first sexual intercourse. In many cases, compression can solve the bleeding problem.

Most of the patients will nevertheless need a surgical intervention (frenuloplasty with or without circumcision) within a short time to achieve a good cosmetic result and prevent further bleeding episodes in the future. Some patients need immediate surgical intervention with local or general anesthesia due to severe bleeding.

Paraphimosis can also occur in patients with untreated phimosis during sexual intercourse. The main problem is relative phimosis with a foreskin that can be moved back in a flaccid penis but is too tight when the penis is fully erected. Patients are often not circumcised because the clinical examination is with flaccid penis and urologists often do not ask about problems during erections.

The therapy of paraphimosis is compression and manual reposition of the foreskin – only in rare cases, a surgical intervention like dorsal incision or immediate circumcision is needed. To prevent the problem of paraphimosis, we recommend or offer circumcision generously to patients with relative phimosis.

b) Priapism Prolonged erections and priapism can have different reasons such as leukaemia or hypercoagulation. Priapsm is classified as sexual trauma when caused by wrong dosage of erectile aids. This problem is caused by penile injection therapy much more frequently compared to PDE-5-inhibitors or transurethral application of erectile aids. In early and less severe cases, cooling of the penis can be a sufficient therapy. In severe cases, puncture of the cavernous bodies and injection of diluted noradrenalin is mandatory.

Cock rings causing severe incarceration of the scrotum

c) Penile fracture The rupture of the tunica albuginea of the erigated penis is caused by sexual action in most cases.

Patients feel sudden pain and a fast loss of erection. They present at the Department of Urology with a large hematoma of the penis.

Therapy is an early operative revision with suture of the corpus. Only in extreme situations, the corpus spongiosum and urethra is also injured. In patients with hematuria during penile fracture, the urethra should be checked. d) Penile strangulation A rare type of penile trauma is strangulation with constricting devices placed around the penis (cock rings) for auto-erotic purposes or to maintain longer erections. In some cases, the device cannot be removed by the patient at the end of the sexual “procedure” because of a swelling of the penis.

Patients develop a kind of priapism, leading to incarceration, thrombosis of the corpora cavernosa and ischemia. Additionally, the patient might suffer from urinary retention.

e) Direct open trauma of the penis Open trauma of the penis might happen due to dislocation of an intrauterine contraceptive device (loop) into the vagina or due to piercings worn by the female or male partner during intercourse.

Injuries caused by a deep bite during fellatio have also been reported – this could lead to an infection with necrotising fasciitis in worst case.

Unfortunately, they sometimes present in the clinic many hours or even days after the start of the incarceration when severe damage to the penile tissue has already happened. The first task for the surgeon is to remove the ring. This might be time-consuming, therefore the physician should not forget to place a suprapubic urinary catheter first before starting with the ring. When patients present early (<10 hours) with grade one to three injury, puncture of the corpora and aspiration of the blood may lead to detumescence and allows removal of the ring without destroying it. In most cases, however, the surgeon has to cut the ring.

The main problem are metal rings. Thin ones can be detached with tongs or a device for cutting finger rings which may be in supply at the Department of Traumatology. Another possibility are diamond cutters to be borrowed from oral surgery. However, dealing with a stainless steel ring of more than one centimetre in size placed around the basis of the penis and the scrotum, only a hand-held power tool (power cut) provided by fire fighters could help.

After all cases, the patient should have an urological follow-up including uroflowmetry because urethral strictures may occur as a late complication which can be treated either with endoscopic incision (laser or cold knife) or with urethroplasty according to length and severity of the stricture.

Foreign bodies in the bladder are more frequent in women than in men due to the length of the urethra.

Various objects like cables, pencils or needles have been found in bladders in our clinical experience.

Even when the end of the object is still out of the body, it is reasonable to do a fluoroscopy before trying to pull it out, to see which size and shape the part of the object inside the bladder has.

We have seen electric cables forming a knot inside the bladder which had to be milled using the stone punch before removing it. A pencil in the bladder a) Fluoroscopic view of an electric cable inserted through the urethra into the bladder could be broken with the holmium laser, the pieces were removed with an endoscopic grasper. Candles or b) Cable after removal in parts Monday, 19 March 2018

Under general anesthesia, we first placed a thin part of iron sheet between the metal ring and the skin to prevent skin injury by the power tool.

We used saline and an irrigation system of TUR-P for cooling and had to place a fire-proof drapery on the patient. The anesthesiologist was adviced to use normal air instead of pure oxygen due to flying firebrands. After removal of the ring, the penis was disinfected and draped (sterile) to remove necrosis and repair the damaged skin. In other more severe cases, the necessity of penile (semi-)amputation has been reported when there was already an ischemic necrosis of the distal part.

Some years ago, a special injury was called “Morbus Kobold” in Germany, named after a type of vacuum cleaner manufactured by the Vorwerk Company. Several men held their penis into the machine for auto-erotic purposes, and got severely injured by the rotating parts. The company was informed about this risk during the latter part of the 1970s and changed the construction of the vacuum cleaner to prevent these injuries.

Trauma of scrotum and testes A minority of testicular torsions occur during sexual intercourse. Therefore, patients with persistent testicular pain during or after intercourse should see a physician immediately because the operative therapy has to be carried out within five to six hours to prevent damage of the testicular tissue due to ischemia.

There are reports of incarceration of the testicle between the pelvic bones of the partners during rough sexual practices leading to a rupture of the tunica albuginea – these are also rare cases and have to be reconstructed during open surgery.

Some patients using cock rings or other constricting devices like cords not only pull the penis through the ring but also the scrotum with the testicles. This may lead to severe swelling, incarceration and ischemia. In these cases, the scrotum has to be opened too during the operative revision after removal of the constricting device (see figure) and the testicles have to be inspected. Necrotic tissue has to be removed.

Conclusion Sexual trauma of the urethra, bladder or male genital organs can be demanding due to the wide variety of mechanisms of injury and the diversity of foreign bodies used for auto-erotic stimulation or during sexual intercourse. Removal of foreign bodies requires care, manual skills and often interdisciplinary cooperation.

Monday 19 March 10.30-12.00: Thematic Session 18, Complications in external genitalia surgery

EUT Congress News

15

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.

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

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

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

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

T115 STEPS Advert 270 x 194.3.indd 1

16/02/2018 09:27

EAU 2018, COPENHAGEN, 16–20 MARCH 2018, IPSEN SATELLITE SYMPOSIUM

Optimising patient management in urogenital cancers Chaired by Dr Maria Ribal (Spain), on Saturday 17 March Dr Peter Busch Østergren (Denmark) The significance of testosterone and gonadotropin suppression in advanced prostate cancer treatment Achieving the lowest levels of testosterone possible, combined with androgen suppression, has been shown to delay disease progression and increase overall survival in men with advanced prostate cancer. Dr Østergren presented key data from a recent study, which demonstrated that androgen deprivation therapy (24-week triptorelin depot) resulted in significantly lower testosterone levels compared with subcapsular orchiectomy in advanced prostate cancer.

Professor Morgan Rouprêt (France) Predicting the future of PDD - blue skies or dark clouds Prof. Rouprêt provided an overview of the future of imaging modalities in non-muscle invasive bladder cancer (NMIBC). Enhanced imaging techniques, such as photodynamic diagnosis (PDD), can help to identify suspect lesions, which may result in increased tumour 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.

REGISTER NOW Join us in the spectacular city of Paris, France, for the 36th World Congress of Endourology, the world’s foremost meeting dedicated to minimally invasive urologic surgery. Assembling today’s global leaders in endourology, WCE 2018 will provide unparalleled opportunities to expand your education, enhance your skills and exchange ideas.

Abstracts Now Open!

Professor Petri Bono (Finland) Current strategies and future challenges in 2nd line therapy in advanced RCC Led by Prof. Bono, this interactive presentation focussed on two patients with advanced RCC who had progressed following 1st line vascular endothelial growth factor (VEGF)-targeted therapy. An overview of current treatment guidelines in this setting, alongside data from recent clinical trials of targeted therapies and immuno-oncology agents, were presented and discussed.

Learn more and submit your abstract at

www.WCE2018.com

Please visit the Ipsen booth E15 CBZ-ALL-000561 13 February 2018

16

EUT Congress News

Monday, 19 March 2018

Getting ready for penile transplants: A novel option?

Research advances may hopefully improve the success of penile transplants Dr. Nikolai Sopko Chief Resident, Urologic Surgery Department of Urology The Johns Hopkins School of Medicine Baltimore, Maryland (US)

associated risks including infection and malignancy.

Psychological counseling and support is continued following the procedure. Informing society and organ donors of the benefit of this procedure to facilitate the donation of this very intimate organ is also important.

To this end, the South African team created a neophallus for the donor, which was critical for the consent of the donor’s family4.

To date, penile transplantation has been performed for complete loss of penile tissues either due to trauma or iatrogenesis. Likely, this will be the largest population Penile transplantation is a novel treatment strategy for of patients who will benefit from penile severe penile disfigurement. In reconstructive surgery, transplantation. Complications of ritual circumcision replacing like tissues with like tissues is the goal. result in varying degrees of penile tissue loss in 250 Given the penis’ complex architecture required for its young men per year4. The protracted military conflicts functions of fluid transportation and penetrative in the Middle East with the extensive use of buried intercourse, no other tissues in the body are similar. improvised explosive devices and improved survival in battlefield trauma has resulted in large number of Phalloplasty using soft tissues from the arm, leg, or young soldiers with disfiguring genital trauma. Other other areas achieve satisfactory cosmetic results. indications include congenital penile disfigurement in However, neophalluses have no erectile capability the setting of bladder exstrophy and disorders of without implanting a penile prosthesis, which is sexual development. There is no rigorous data, as of delayed from the time of transplantation by yet, to determine whether penile transplantation will approximately one year to allow the development of be desired for gender reassignment in the transgender protective sensation and is fraught with complication population.

High magnification view shows no rejection on transversal section of transplanted penile shaft. (Hematoxylin-eosin staining; rates approaching 40%1. The South African experience original magnification: ×200.) Photo: European Urology Archives suggests that even when a neophallus is successfully Thus, one of the most important factors for the implanted, it cannot withstand the physical demands indication of penile transplantation will be the patient’s of frequent sexual intercourse. Neophallus fluid Allotransplantation for Complex Genitourinary psychological stress. However, it may provide natural wishes and desires for their genital reconstruction. If Reconstruction. J Urol 2017. DOI:10.1016/j.juro.2016.10.134. transport capabilities are also less than ideal with erectile function and more robust fluid transport only cosmesis is desired, then a reconstructive complications including fistulas and strictures at rates neophallus may be sufficient. If the patient desires 3 Hu W, Lu J, Zhang L, et al. A Preliminary Report of Penile function than current phalloplasty procedures can of 42% to 65%2. With the increasing experience and Transplantation. Eur Urol 2006; 50: 851–3. offer. Advances in research of immunosuppression and include frequent sexual intercourse and/or robust success in vascularized composite allotransplantation 4 van der Merwe A, Graewe F, Zühlke A, et al. Penile penile transplantation will hopefully improve the urinary transport then replacing tissue with like tissue (VCA) such as face and arm transplantation, penile allotransplantation for penis amputation following ritual success of this operation, minimize its side effects, and using penile transplantation may be the best option. transplantation has become a reality. circumcision: a case report with 24 months of follow-up. offer an effective management for the very difficult to One of the biggest impediments to widely adopting Lancet (London, England) 2017; 390: 1038–47. treat condition of severe penile disfigurement.

To date, there have been four attempts at human this treatment modality is the significant risk 5 Cetrulo CL, Li K, Salinas HM, et al. Penis Transplantation: penile transplantation, three of which were successful. associated with life-long immunosuppression. These First US Experience. Ann Surg 2017; XX: 1–6.

References The first documented case was performed in 2006 in include hypertension, renal failure, neuropathy, 1 Sopko NA, Tuffaha SH, Lough D, et al. Penile China on a 44-year-old man who lost his entire Allotransplantation for Complex Genitourinary Monday 19 March infection, and increased risk for developing a pendulous penis in a traumatic accident eight months malignancy. Exciting immunosuppression research 10.30-12.00: Thematic Session 19, Transgender Reconstruction. J Urol 2017; published online March 10. prior. Although there were no signs of rejection and seeking to achieve immune tolerance of the recipient’s DOI:10.1016/j.juro.2016.10.134. healthcare: A primer for the urologist the patient was able to spontaneously void on immune system to the transplanted organ by using 2 Sopko NA, Tuffaha SH, Lough D, et al. Penile post-operative Day 10, the transplanted penis was novel small molecules and stem cell infusions may removed on post-operative Day 14 due to “a severe lead to therapies that minimize the current risks of psychological problem of the recipient and his wife”3. immunosuppression. This would greatly alter the The second attempt and first successful human penile risk-benefit ratio of penile transplantation and likely transplantation was performed in December 2014 at greatly increase its acceptance. the Tygerberg Academic Hospital in South Africa4. The using Hemera Pulsed Thulium laser 21-year-old man lost his pendulous penis due to Another obstacle to broad implementation, as with with updated settings infectious complications of a ritual circumcision most other forms of VCA, are the highly skilled performed three years earlier. This case has the multidisciplinary teams including specialists such as longest documented follow-up of 24 months with psychiatrists, counselors, organ procurement encouraging results. coordinators, urologists, and plastic surgeons. They are required for patient identification, assessment, counseling, transplantation coordination, and By 24 months, the patient did not experience an episode of rejection, was having unaided erections performing the technically challenging procedures of Groupe Urologie Saint- Augustin - Bordeaux (Fr) penile harvest and implantation. Unlike kidneys with normal orgasm and ejaculation that was sufficient enough to impregnate his girlfriend. Most transplantations, which on average require three importantly, the patient has fully accepted his anastomoses – one artery, one vein, and a urinary transplanted penis and his quality of life is anastomosis, the penis may require up to 10 small to In this video, we will present a laser prostate enucleation using micro-anastomoses depending on the anatomy and significantly improved. His immunosuppresion updated settings, along with a modified en bloc dissection. At last surgical approach – two dorsal arteries, two regimen consists of prednisone, tacrolimus, and year’s ESUT session, we showed an original approach to enucleation azathioprine and complications thereof include acne cavernosal arteries, two external pudendal arteries, and hypertension, which resolved with dose deep dorsal vein, two dorsal nerves, and the urethra, using a pulsed Thulium laser. adjustment, and a successfully treated episode of a not including joining the tunica albuginea and skin. supra-patellar bursa fungal infection. The same group None of the successful cases have employed all of For better performance, we changed settings to achieve a better has recently performed their second penile these anastomoses but variations thereof due to transplantation (4th penile transplant overall) April recipient anatomy and technical feasibility. bubble effect, thus achieving a clearer enucleation plane.

2017, of which the results and follow-up have not been published4.

More research needed We will show how the thulium laser used in a pulsed mode can be As with all novel clinical endeavors, research is The second successful penile transplant was required to better understand the challenges that lie combined with a minimally invasive endoscopic technique to treat performed at the Massachusetts General Hospital May ahead. Given the uniqueness of penile architecture, large prostatic adenomas.

2016 after the 64-year-old recipient had a penectomy function, and certain tissues, it is unclear based on 5 for penile cancer four years prior . After seven months prior VCA or solid organ transplantation how penile of follow-up the patient has had two acute rejection tissues may undergo rejection and how this will affect episodes, has partial penile sensation and erectile its function. Skin is commonly considered one of the function, and is voiding spontaneously. In both most immunogenic tissues in VCA and often reported successful penile transplantations, recipients monitored for early signs of rejection. Our preliminary required several additional procedures for research (not yet published) suggests that the urethra complications including hematoma evacuation, eschar may also elicit a rejection response. Given the debridement, and urethralcutaneous fistula closures. sensitivity of penile microvasculature, early rejection may be detected by new onset loss in erectile function.

Thorough patient counselling Penile transplantation basic science and translational Given that penile transplantation is life-enhancing and science is complicated by the poor recapitulation of not life-saving, thorough discussions with the patient penile transplantation in rodent models and the regarding the risks and benefits of the procedure are ethical challenges in using larger species such as paramount. In both documented cases, patients canines and monkeys. There are many exciting underwent extensive psychological evaluation with opportunities and discoveries to be made to better assessment of motivation and treatment adherence. understand and optimize penile transplantation.

Treatment teams emphasized discussions regarding Procedure performed with 200 W possible psychological rejection of the graft, unmet Penile transplantation is an ethically and technically Hemera ® Thulium Rocamed Laser expectations of treatment outcomes, graft failure, and challenging treatment for the devastating loss of social stigmatization. Patients were also counseled on penile tissue and function. It includes the significant the need of life-long immunosuppression and the risks of life-long immunosuppression, surgery, and

ENUCLEATION OF THE PROSTATE

Dr J.B Roche

Pre-recorded video

March, 17th 16:54

eUro Auditorium (Level 0)

Monday, 19 March 2018

EUT Congress News

17

Bone metabolism and stones No specific treatment is available for efficiently counteracting impaired bone metabolism Prof. Jean-Philippe Haymann Sorbonne Université Hôpital Tenon Paris (FR)

demineralization whereas the latter only accounts for increased intestinal calcium absorption. Daily calcium excretion depends upon several factors including calcium diet, intestinal absorption and bone resorption: in PHPT patients, an increased calcium intake would decrease PTH level and thus presumably bone resorption but at the expense of an increased calciuria (i.e. would increase stone risk factors). PHPT is encountered in 3 to 7% of hypercalciuric renal stone patients.

High serum PTH is associated with 63% of osteoporosis and 35% of fracture15, as increased intracortical bone turnover results into trabecularisation of the inner cortical bone and increased cortical porosity responsible for impaired bone strength. In fact, cortical bone strength is probably more dependent upon Moreover, bone resorption maybe due to a shorter cortical porosity than changes in mineralization or remodeling period with a formation period too short to mechanical properties of the bone matrix. However, in allow a complete mineralization of osteoid bone (i.e.

PHPT, high serum calcitriol is also deleterious on bone new unmineralized bone matrix), and/or an increased metabolism through activation of the vitamin receptor remodeling rate activation frequency (activation of a (VDR) localized both on osteoblasts and osteoclasts, new remodeling site at any random locus on the leading to synthesis of unmineralized osteoid bone trabecular surface) leading also to cortical thickness which is ultimately degraded. Of notice, the hallmark decrease and cortical porosity and/or a decreased features of bone demineralization and hypercalciuria mineral apposition rate. Bone demineralization is most encountered in PHPT require the combine action of of the time related to multifactorial factors including PTH and VDR activation (altogether with an activation age, smoking status, low body mass index, a familial of the Calcium receptor (CaSR) in the ascending limb of bone demineralization history, long course steroid Henle loop). intakes, early age at menopause.

Bone demineralization and VDR signaling Several lines of evidence demonstrate a VDR Renal stone disease is also considered as an independent risk factor for bone demineralization and activation independently of serum PTH in idiopathic hypercalciuric renal stone accounting for the fracture (especially for the spine site and to a lesser extent for cortical rich sites) both in male and female phenotype: increased intestinal calcium absorption, stone formers1,2,3. Despite some controversial reports, bone resorption and hypercalciuria. Indeed, a high the general view is that in idiopathic hypercalciuria, serum calcitriol activating VDR signaling, noteworthy low BMD is due principally to decreased bone in guts and bones, is encountered in 30-70% of cases7 formation in the face of normal bone resorption, i.e. in idiopathic hypercalciuric renal stone formers (50% an increased osteoid volume and surface and reduced in our experience). So far, no etiology such as osteoblast numbers4. sarcoidosis could be found in our series, thus leading to a final diagnosis of ‘idiopathic hypercalcitriolemia’.

In other reports, histomorphometric data showed decreased bone formation rates and increased Several hypothesis are currently under investigation, not mutually exclusive, to explain this biological mineralization lag times altogether with increased resorption surfaces5,6. The discrepancy between the feature: a polymorphism of CYP 24A1 (24 hydroxylase), different reports is probably explained by the fact that a FGF 23 counter-regulation defect and/or a decreased idiopathic hypercalciuria is a heterogenous entity with soluble functional klotho. Indeed, a decreased CYP bone metabolism differences between gender and may 24A1 is expected to increase calcitriol, through an impaired degradation, and alternatively, relative low in some cases also include fasting hypercalciuria and secondary hyperparathyroidism where bone resorption FGF 23 or soluble Klotho plasma concentrations would and formation are reported to be increased7. impair a negative feed-back on CYP 27B1 (un alpha hydroxylase), i.e. favor calcitriol synthesis.

Among the different issues accounting for bone demineralization, an inadequate calcium restriction Nevertheless, activation of VDR may also occur in diet was pointed out as a key factor. Nevertheless, hypercalciuric stone formers with normal serum idiopathic hypercalciuria was demonstrated as a calcitriol as speculated by some authors16. Indeed, a relevant determinant per se8,9,10, thus raising the issue VDR polymorphism is an attractive hypothesis to of the underlying pathophysiological process: is it a explain their phenotype either through upregulation primary hyperparathyroidism, a primary bone of VDR density (on enterocytes and osteoblasts/ disease, a primary renal calcium leak, a calcium osteoclasts) or through a (constitutive) activation of dysregulation due to unravel hormonal disorders VDR signaling pathway (which may among other affecting a gut-kidney-bone axis? hypothesis, involve the interplay of sirtuin-1 on posttranslational VDR acetylation leading to Pathophysiology: A defect in calcium homeostasis 1,25D-VDR signaling amplification)17.

Several studies suggest that bone demineralization is due to a negative calcium balance despite an However, these potential mechanisms remain at increased calcium absorption by the guts11,12. Indeed, present mostly unravel despite significant pieces of 24 hours urine calcium excretion is higher than gut evidence in animal models. Indeed, a high VDR net absorption. This negative balance means that expression was reported in renal stone formers16 and body calcium content, i.e. bone calcium stores, will genetic hypercalciuric stone-forming (GHS) rats which slightly decrease everyday13. We know from human also experience bone resorption. A VDR transgenic physiology that net calcium bone influx is zero during mice model, shed in light the relevance of VDR adulthood but positive during growth and negative expression when expressed selectively in guts and noteworthy during menopause. bones: bone demineralization mechanism is related to an increased bone remodeling and mineralization In stone formers, the order of magnitude of calcium lag time. imbalance is however presumably small within 1 mmole range/day (i .e. 40 mg/day)14 and thus cannot Indeed, in osteoblasts, calcium phosphate inhibitors account by itself for hypercalciuria: increased calcium such as pyrophosphates (PPs) are secreted and inhibit intestinal absorption is indeed a key counterpart of osteoid bone mineralization18. As a matter of fact, scarce the picture. Therefore, if we assume that calcium body bone histomorphometry and CT scan performed in content is around 1000g, we can theoretically human hypercalciuric renal stone formers, looks similar calculate that a loss of 1 mmole of calcium everyday to bone structure reported in genetic hypercalciuric will be responsible for a 10% decrease of calcium stone-forming rats models19. Alternatively, though not bone mass in seven years (which means a significant mutually exclusive, other factors such as increased low bone mineral density). This daily negative balance Calcium sensing receptors may be at play in humans as can be even greater if the patient is under a calcium shown in animal models and account at least for some restricted diet: indeed, net calcium intestinal excretion features of the phenotype. may then also occur in this case.

Bone demineralization and renal tubular disorders Bone demineralization and Primary Hyperparathyroidism The association of nephrocalcinosis in patients with (PHPT) lithiasis and bone demineralization drives the Parathyroid hormone (PTH), was pointed out early in diagnosis towards renal tubular disorders, the ‘70s as a relevant determinant of bone status in noteworthy renal distal tubular acidosis and renal renal stone patients. Indeed a high PTH increases phosphate leak (NaPi 2a or 2c mutations or dent serum calcitriol, which both exert bone disease). Though nephrocalcinosis is a rare entity, the Bone demineralization is a heterogenous entity including either a primary bone matrix disorder, a net bone resorption or the involvement of both processes to various extent.

18

EUT Congress News

Bone demineralization prevention requires in most cases a normal calcium diet (i.e. 800 mg/day) (Photo: EUT Archives)

study of the underlying biological features provide interesting insight into the pathophysiological processes linking kidney and bone and gut. Indeed, in renal distal tubular acidosis, calciuria is most of the time within normal range whereas very low urinary citrate (due to metabolic acidosis leading to an increased tubular reabsorption of luminal citrate in the proximal tubule segment) account for renal stones and nephrocalcinosis.

Diagnosis is performed upon the presence of a metabolic acidosis with a normal plasma anion gap and low urinary ammonium excretion (hypokalemia is also a usual feature)20. Bone demineralization is obviously not mediated by PTH or calcitriol / VDR signaling and would be characterized both by a low bone formation rate and a low resorption (increased osteoid bone and impaired bone microarchitecture characterized by a decrease in trabecular number)20.

Metabolic acidosis-induced calcium efflux from bone is currently considered to be related to phosphate buffer mobilization. In animal models, a RANK ligand mediated increased activity of osteoclasts is reported altogether with an inhibition of osteoblastic immediate early response genes controlling matrix formation21.

Homozygous and compound heterozygous mutations of the sodium dependent co-transporter NaPi-IIc, cause hereditary hypophosphatemic rickets with hypercalciuria (HHRH), a disorder characterized by renal phosphate-wasting resulting in hypophosphatemia, elevated 1,25(OH)2 vitamin D levels, hypercalciuria, rickets/osteomalacia, kidney stones and nephrocalcinosis22. Hypophosphatemia, nephrocalcinosis and bone demineralization have been also reported in patients with mutations in NaPi-IIa23. Of notice, as mentioned above, stimulation of VDR seems at play in this tubular disorder as a high calcitriol level is reported, which may further impair bone density in addition to hypophosphatemia.

Bone demineralization and intestinal disorders Gut malabsorption especially after large gut resection of jejunum or ileum segment is often responsible for bone demineralization and renal stones. However in this case, calciuria is low as intestinal calcium absorption is occurring in the proximal gut segments, thus accounting for a secondary hyperparathyroidism where bone resorption and formation are presumably increased.

Conversely, hyperoxaluria is the main stone risk factor as increased content of free oxalates in the gut lumen (due to malabsorption preventing oxalate binding to calcium or magnesium) leads to enhanced absorption in the colon segment. This process accounts for active calcium oxalate monohydrate stones, which are oxalate and not calcium dependent: in this setting there is a direct link between gut-bones and gut-stones but no link between bones and stones.

Here, bone metabolism is dependent upon low calcium and a high PTH whereas VDR activation is probably not occurring as 25OH vitamin D is most of the time low due to gut malabsorption.

Idiopathic hypercalciuria In some cases, renal stone patients with hypercalciuria experience a positive calcium balance due to various conditions such as massive calcium intakes, and/or high plasma concentrations of estrogen, progesterone or prolactin which favor bone formation. However, patients having an idiopathic hypercalciuria often excrete more calcium than they absorb, reflecting a net loss of total body Ca, thus pointing out a complex interplay between guts, bones and kidneys.

From experimental and human data, VDR activation (related to either a high serum calcitriol or increased VDR number / sensitization) appears as a key actor potentially accounting for the clinical and biological features with a demineralization resulting from an imbalance between a low bone formation and a normal resorption. Other mechanisms at play remain to be elucidated. To date, no specific treatment is available for counteracting efficiently impaired bone metabolism.

However, bone demineralization prevention requires in most cases a normal calcium diet (i.e. (800 mg/day) and in the setting of osteoporosis a specific management which may include chlorothiazides, citrates and/or biphosphonate.

Assessing bone metabolism while performing histomorphometric analysis in idiopathic hypercalciuric stone formers with severe osteoporosis should be considered for an optimal management as bone biochemical markers are of limited clinical use.

References 1. Melton LJ , Crowson CS, Khosla S, et al. Fracture risk among patients with urolithiasis: a population-based cohort study. Kidney Int 1998;53:459–464.

2. Denburg MR, Leonard MB, Haynes K, et al. Risk of fracture in urolithiasis: a population-based cohort study using the Health Improvement Network. Clin J Am Soc Nephrol. 2014; 9:2133.

3. Lauderdale DS, Thisted RA, Wen M, Favus M. Bone mineral density and fracture among prevalent kidney stone cases in the Third National Health and Nutrition Examination Survey. J Bone Miner. 2001; 16:1893–1898.

4. Malluche HH, Tschoepe W, Ritz E, et al. Abnormal bone histology in idiopathic hypercalciuria. J Clin Endocrinol Metab 1980;50:654–658.

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.

Tuesday 20 March 08.00-13.30: Plenary Session 7, Stones

Monday, 19 March 2018

Multi-tract PNL approach PNL will keep its place in cases of large stones and complex anatomy Otas Durutovic Member, Endourology Group- ESUT Associate Professor of Urology Clinic of Urology University of Belgrade Belgrade (RS) Percutaneous nephrolithotomy (PNL) is still considered as a first-line treatment in large stones, despite many modern retrograde “per vias naturales” techniques that are becoming more popular in bigger and bigger stones. There is no doubt that for staghorn stones PNL is a gold standard.

From its beginning PNL underwent many changes and developments. Tract formation with Alken telescopic dilators was changed firstly with balloon dilators, but as the instrument size was decreasing, also other single-step dilation techniques were developed. The next field of interest was tract size, as it was considered as an important step toward decreasing bleeding, hemoglobin drop, that were also associated with septic complication. As one of the most common and severe complications, infection and risk of urosepsis were the reason for recognition that intra pelvic pressure (IPP) is a key of this condition. Closed irrigation systems and a consequent high pressure, low flow and visualization, led PNL to long duration and high risk of developing sepsis. That is why recent developments were focused on flow, decrease of pressure (IPP) by low inflow, high outflow and vacuum cleaner effect.

Virtual forceps, “forceps” made by direction of flow, is a main goal in creating modern, miniaturized PNL instruments. The main advantage of standard, large PNL instruments which is removal of big fragments, and offering speed and efficacy, can now be substituted by high laser energy delivered on the stone, and high outflow with clearance of the dust or fragments created.

Obtaining the precise, planned and desired access to a specific part of the pyelocaliceal system is the first and crucial step for a successful and safe PNL. Efficacy and safety are two ultimate goals, that are present also when large or complex renal stones are treated.

Sometimes it is not easy to fulfil both criteria, especially in cases of the most complex stones and/or pyelocaliceal anatomy.

we should use during tract creation. And these are some of the reasons why urologists in high-volume centers and stone experts, are trying to perform PNL through one puncture; or if more punctures are needed, to use the least number possible. Thus, the “perfect puncture” becomes our goal!

Introduction of flexible instruments, flexible nephroscope, baskets and laser fibers, but also development of ECIRS, have led to a situation that cases that were considered as candidates for multiple punctures were finished through one access.

Despite all previously mentioned considerations, creativity and dedication, the most complex cases demand complex, multiple approaches/punctures.

Complex cases are not associated only with the question of how many punctures and where to create, but also with duration of the procedure.

Duration of the procedure, along with pressure achieved inside the renal collecting system are two factors influencing the risks of septic complication.

Multiple tracts formation leads to opening of more vessels, which are potential causes of infection. In cases where infection occurred deep inside the stone, and released during lithotripsy, this mechanism and possible risk of intraoperative sepsis must be taken into account. That is why creation of multiple tracts should be done precisely, with the aim to avoid unnecessary torqueing and movement, which can lead to parenchymal laceration and increased bleeding.

If we investigate published studies about multiple tracts and PNL outcome, we can find studies concluding that there is no difference in terms of efficacy and complication rates; but on the other hand, we can find data about increased transfusion rate when more tracts were created.

(Figure 2)

Figure 2: Number of tracts and the need for transfusion

Use of smaller instruments Modern PNL era offers the possibility to use smaller instruments, as it is well documented that the smaller the instruments are, the smaller the need for transfusion. (Figure 3)

Still a challenge The most complex stone cases remain a challenge for urologists even today despite all the improvements made in endourology and stone treatment. Despite the fact that we can combine techniques, use them separately, one following another (“sandwich therapy”), or at the same time (ECIRS), complex stones and complex anatomy clearly requires the necessity of multiple punctures.

Figure 3: Association of instrument size and need for

Puncture is the crucial step of PNL, as already said, not transfusion just in term of efficacy, but also safety. Puncture should be considered and created much earlier before coming to the operating theatre, during investigation and imaging, sometimes making additional imaging necessary prior to a decision - which technique to use and how to approach to the stone. Tract formation brings additional risks, emphasizing the possible steps

Figure 1: Tight infundibulum and parallel calyces to the Amplatz making stones unapproachable even with flexible instruments (Courtesy of Dr. Cesare Scoffone, ECIRS Book)

Monday, 19 March 2018

Figures 4, 5, 6 & 7: Multiple tracts bilateral multi stage PNL. (Hegarty NJ, Desai MM, J Endourol. 2006)

Figures 8, 9, 10, 11, 12 & 13: Author’s collection – combination of two tracts and flexible nephroscope for extraction of stone from rigid nephroscope unapproachable calyx

At this time, we can say that treatment of complex stones today becomes an interesting and creative issue. What are the alternatives we have today? Are we going to use standard instruments, bigger than 22 Fr? Or are we going to do MiniPNL, or are we going to combine standard PNL with flexible nephroscope, of RIRS (ECIRS), or maybe to create multi-MiniPNL? Selecting the approach should be case-dependent.

Sometimes, even when multiple tracts are created, lithotripsy cannot be completed within one session. Multiple sessions with multiple tracts are reserved for the very large and complex cases.

Here are few images when four tracts were created on the right side, in a case of complete bilateral staghorn stones, which were completely removed with two and three sessions of PNL procedures.

In cases where complex anatomy is a bigger issue than stone size, or where stone distribution is associated with complex anatomy, we can try to combine multiple tracts with flexible instruments, and try to approach and extract the stones from calyces that can be entered. Here are the images that present this kind of technique.

safely low level, but the level that can maintain space for work and control of the procedure. Vacuum cleaner effect, “virtual forceps”, can also decrease risk of fragments loss to the calyces, which at the end make them residual.

Retrograde intrarenal surgery (RIRS) will continue to develop, and in experienced hands treating bigger stones, but PNL will keep its place in cases of large stones, and in cases with complex anatomy, and also in cases with failed previous less invasive treatments.

Informing the patient about results of the procedure based on the case complexity is possible when we talk about PNL. Concerning RIRS/ECIRS, there are no available nomograms that can determine the complexity of the case. All results are based on the size, or location of the stone – lower pole, pelvic, etc.

This could help us in selecting the most effective procedure, when considering PNL if the complexity of the case can be overwhelmed by multiple tracts. In experienced hand, more tracts do not necessarily bring more risks to the patient.

References: It is difficult to advise a urologist on how to direct 1. Hegarty NJ, Desai MM Percutaneous nephrolithotomy their intentions concerning treatment selection of requiring multiple tracts: comparison of morbidity complex cases. Sometimes treatment options depend with single-tract procedures. J Endourol. 2006 on available instruments and tools, while at times it is Oct;20(10):753-60. a matter of the operator’s personal preference, his/ 2. Ruhayel Y et al. Tract Sizes in Miniaturized Percutaneous her skills, experience and results. With so many Nephrolithotomy: A Systematic Review from the options offered by guidelines, personal and critical European Association of Urology Urolithiasis Guidelines Panel. Eur Urol. 2017 Aug;72(2):220-235. presentation of the possible techniques and results, consulting the patient should also become a standard. 3. Cho HJ et al. Percutaneous nephrolithotomy for complex Further improvements The future of PNL lies in further improvement of its two most important steps.

First step, puncture and tract creation must be precise and gentle, with single-step dilations becoming a gold standard. It could lead to less bleeding, less risks of septic complications, but also better vision during the procedure. The use of pre-operative imaging and selection of the optimal calyx or calyces, with assessment of the angles between calyces, distribution of stones, makes preparation for the PNL a very creative job!

Better vision takes us to the “second pair of gloves” called safety! In the literature we can find proofs that more tracts are one of the reasons for possible septic complications. With smaller size instruments, this risk can be decreased. Already mentioned, pressure and flow that nowadays becomes the crucial point of interest in further development of instruments, can take pressure during the PNL procedure to a

renal calculi: is multi-tract approach ok? Can J Urol. 2012 Aug;19(4):6360-5.

4. Maghsoudi R et al. Number of tracts or stone size: which influences outcome of percutaneous nephrolithotomy for staghorn renal stones? Urol Int. 2012;89(1):103-6.

5. Singla M.et al. Aggressive approach to staghorn calculi-safety and efficacy of multiple tracts percutaneous nephrolithotomy. Urology. 2008;71(6):1039–42.

6. Atalay HA et al. Impact of personalized threedimensional -3D- printed pelvicalyceal system models on patient information in percutaneous nephrolithotripsy surgery: a pilot study. Int Braz J Urol. 2017 MayJun;43(3):470-475.

7. Chen J., et al. Multiple tracts percutaneous nephrolithotomy assisted by LithoClast master in one session for staghorn calculi: report of 117 cases.

Urolithiasis. 2014;42(2):165–9.

8. Rashid AO and Fakhulddin SS. Asian Risk factors for fever and sepsis after percutaneous nephrolithotomy. J Urol.

2016 Apr;3(2):82-87.

9. Liang T. et al. Multi-tract percutaneous nephrolithotomy combined with EMS lithotripsy for bilateral complex renal stones: our experience. BMC Urol. 2017 Feb 28;17(1):15 10. Verma A. et al. Complex multiple renal calculi: stone distribution, pelvicalyceal anatomy and site of puncture as predictors of PCNL outcome. Springerplus. 2016 Aug 17;5(1):1356.

Monday, 19 March 10.30-12.00: Thematic Session 10, Management of complicated urinary stone disease

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Reading and interpreting MRI ESU activities on MRI underlines crucial role of emerging technologies Dr. Jochen Walz Dept. of Urology Institut PaoliCalmettes Marseille (FR)

As urologists we have the foresight to keep up with emerging technologies and cutting-edge research, and rightfully so as this benefits our patients and daily practice. Additionally, we also see the growing necessity of being able to read and interpret Magnetic Resonance Imaging (MRI).

Several ESU Courses and HOT sessions on MRI are in the programme of the 33rd Annual EAU Congress (EAU18) here in Copenhagen. The HOT sessions include the ESU/ESUT/ESUI Hands-on Training Course in MRI Fusion Biopsy organised by the ESU with the EAU Section of Uro-Technology (ESUT), and the EAU Section of Urological Imaging (ESUI).

This session provides an overview on MRI reading, the basics on techniques and different prostate biopsy approaches. Technical considerations, transrectal and transperineal approaches are examined in the session as well. Participants will have the opportunity to apply learned concepts on different fusion biopsy machines and, at the end of the session, they will further understand advantages, handling of and the limits of MRI ultrasound fusion biopsies.

MRI plays an increasingly important role in the diagnosis of prostate cancer (PCa). It is already the recommended standard for repeat biopsy and will potentially be the recommended standard for first biopsy as well. Thus, the time has come to include reading and interpreting MRI as a urological activity.

Adding to our skills set A few decades ago, urologists did not know how to read and interpret a CT scan. Today, reading a CT scan is a regular task. We have to be as familiar with MRI as we are with CT scan.

HOT in prostate MRI reading for urologists at ESOU18

Another must-attend HOT session is the ESU/ESUI Hands-on Training Course in Prostate MRI reading for urologists. This session offers an exclusive hands-on experience in prostate MRI interpretation designed to give participants a chance to interpret MRIs and receive individual real-time feedback.

Participants are given warm-up exercises prior to the test cases to familiarise them with the sequences and scoring systems. They are provided with their own laptops during the course for the test cases and will then go through their answers together with esteemed faculty members.

Aside from comprehending and making sense of MRI images, it is also crucial that we distinguish good from bad MRI images. Moreover, if we are unaware that there are quality issues with these images at times, the progress of MRI and our own improvement will be stunted. On the other hand, if we are educated about MRI quality, we can discuss, deliberate and work together with radiologists. As a consequence, this will boost the quality standards of MRI, eventually making the adaption of this technology more widespread.

ESU activities on MRI We need to be more familiar and knowledgeable with this imaging and diagnostic tool and the only way to do that is to learn how to read MRI and draw relevant clinical conclusions. The ideal platform is through the courses and Hands-on Training (HOT) sessions of the European School of Urology (ESU).

and update on recent imaging techniques such as multiparametric magnetic resonance imaging (mpMRI), Transrectal Ultrasound (TRUS), Histoscanning and nuclear techniques for PCa diagnosis.

The ESU is on the forefront of making readily available the reading and interpreting MRI to urologists through its courses and HOT sessions.

These highly-informative ESU activities also complement the other sessions at the Annual EAU Congress and meetings, ensuring a well-rounded learning experience for participants.

Monday, 19 March 09.30-13.00: HOT 47- ESU/ESUI Hands-on Training Course in Prostate MRI Reading for Urologists 12.00-14.00: ESU Course 45 Prostate biopsyTips and Tricks

Some ESU courses at EAU18 cover MRI and other imaging modalities such as ESU Course 26 Prostate cancer imaging: When and how to use it, which gives an overview on the currently available imaging tools for PCa, practical information on their use, and a critical assessment of their clinical performance and their limitations. The course includes lectures on prostate MRI, prostate-specific membrane antigen (PSMA) and Choline-PET imaging, staging with computerised tomography (CT) scan, MRI and bone scintigraphy, detection of locally recurrent PCa, and more.

HOT session in MRI Fusion Biopsy

The use of MRI will also be discussed in ESU Course 10 Prostate cancer screening and active surveillance

Dr. V. Kasivisvanathan (right) guides a participant during HOT MRI reading

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EAUN Bladder Cancer Special Interest Group Specialised urology nurses offer compact, insightful session on bladder cancer care Kathryn Chatterton Member, Bladder Cancer SIG Bladder Cancer Clinical Nurse Specialist Dept. of Urology Guy’s and St Thomas’ NHS Foundation Trust London (UK)

the best for our patients. The BC SIG will allow us as a community to come together, share ideas and learn from each other. We as a nursing community can, through the BC SIG, arrange clinical visits to centres of excellence and where participants can observe best practices.

The BC SIG is in the process of collaborating with other urological nursing associations, not just in Europe but worldwide. We intend to exchange practical ideas, discuss differences, share current practices and potential areas of research. We aim to engage organisations including the Society of For the Bladder Cancer Special Interest Group (BC SIG), this year’s International EAUN meeting is an Urologic Nurses and Associates (SUNA) and Australia and New Zealand Urological Nursing Society, ideal way to introduce its goals to the association’s general membership. With its expertise, knowledge (ANZUNS). One of our goals is for the EAUN website and enthusiasm, the BC SIG aims not only to improve to become a robust source of bladder cancer and set standards in bladder cancer (BCa) nursing but knowledge, including dynamic content, chat forums, also provide a dynamic community to all nurses real cases discussion, online webinars, and a listing of masterclasses and courses available in various involved in BCa care.

European centres.

Currently, the BC SIG consists of five members with In-depth BCa session expertise in research, professional development and clinical work (operating theatres, ward and As expected, we offer at this year’s annual meeting a programme that is relevant for all members. Don’t outpatient), and all with a special interest in bladder miss the “Evolution and Management of BCG”, which cancer. The members include; Bente Thoft Jensen (DK), Kathryn Chatterton (UK), Heike Pueschel (CH), provides a refreshing update and overview on how Line Lydom (DK), and Linda Söderkvist (SE) as EAUN Board representatives. We are at present negotiating group expectations and looking forward to sharing these with our members over the next year. We are extremely excited about our forthcoming plans!

Following an over-subscribed 3rd ESUN course in Amsterdam in October 2017 (participants from 18 different countries), we are already planning future courses specifically designed for bladder cancer care.

It was a fantastic forum to learn and share ideas from experts and to network with nurses from all over Europe and as far as Japan and Australia.

As we are all aware, practices differ among countries due to the available range of products, licenses, logistics and costs. At the end of the day we all want

BCG was discovered, its mechanism of action, effects on the bladder and impact on bladder cancer. Specialised nurses often work autonomously in nurse-led intravesical clinics and this session provides updates on evidence-based practice that not only impacts our practice, but also enable us to provide optimal learning to students and better healthcare for patients.

Secondly, a key aspect in Dr. Kees Hendricksen (NL) speaking on substaging of bladder cancer administering BCG is managing the “side effects”.

How do we manage side effects? The session The BC SIG looks forward to welcoming you to this will discuss why side effects occur, how to manage bladder cancer session. Feel free to approach us, these side effects and how to recognise differences share your ideas on how we can take this initiative between minor and major side effects associated forward in future EAUN events. with intravesical BCG administration. We are all aware how troublesome these can be for We are keen to hear your suggestions regarding our patients but with knowledge on how, learning goals and needs, ideas for future courses, why and what, we hope participants will gain or your need for guidelines that may be lacking. further confidence in managing these side effects in their clinics.

Finally, the BC SIG will endeavour to support members engaged in bladder cancer care by providing updated information, courses, interesting To conclude the session, we will examine a case topics for discussion and collaboration within the study regarding key lessons EAUN website. in BCG that will consolidate the sessions’ learning goals We look forward to seeing you at the Green Area, Room 12 (Level 1) at 08.30 Monday 19 March. and insights. Moreover, participants should pick up Join us, ask the experts and be a part of this a clear and practical stimulating BCG session! message with regards to the Monday 19 March careful administration of 08.30 – 09.30: 19th International EAUN Meeting, BCG that underlines its role Thematic Session 10 as a powerful drug with potential complications, SIG Bladder Cancer: Evolution and management including systemic of BCG Group discussion to create a plan implementing the knowledge gained in their own work place absorption, BCGosis.

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