Global Congress on Prostate Cancer 2022: abstract book by mirrorsofmedicine

Abstract book ONSITE (ATHENS, GREECE) & VIRTUAL MEETING 18 & 19 October 2022

ORGANISING COMMITTEE OF THE CONGRESS

Amit Bahl, Bristol Haematology & Oncology Centre, Bristol, UK

Aristotelis Bamias, Medical Oncology, National and Kapodistrian University, Attikon University Hospital, Athens, Greece

Petros Grivas, Medical Oncology, University of Washington and Fred Hutchinson Cancer Research Center, Seattle, USA

Vasileios Kouloulias, Radiation Oncology, National and Kapodistrian University, Attikon University Hospital, Athens, Greece

Dionysios Mitropoulos, Urology, National and Kapodistrian University, Laiko General Hospital, Athens, Greece

Piet Ost, GZA Sint Augustinus, Antwerp & Ghent University, Ghent, Belgium

Athanasios Papatsoris, Urology, National and Kapodistrian University, Sismanoglio General Hospital, Athens, Greece

Ash Tewari, Icahn School of Medicine at Mount Sinai, New York, USA

Bertrand Tombal, University Hospital Saint-Luc, Brussels, Belgium

Anna Zygogianni, Radiation Oncology, National and Kapodistrian University, Aretaieion University Hospital, Athens, Greece +32 3 491

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Palliative radiation in mCRPC –biochemical response and toxicity assessment

Suryakanta Acharya* *Assam Cancer Care Foundation, Lakhimpur, India

Introduction & Objectives: Prostate cancer is the second most common cancer in males worldwide. Many patients develop metastatic castration resistant prostate cancer (mCRPC) during course of the disease despite initial hormone treatment. Palliative radiation to prostate and affected bones brings symptomatic relief along with good biochemical response.

Present study was made to find out biochemical response and toxicity of hemi-body palliative radiation therapy in mCRPC.

Materials & Methods: In 2021, fourteen mCRPC patients were given palliative hemi-body radiation therapy. Hemi-body radiation consists of 6 and 8 Gy dose, delivered to upper hemibody and lower hemi-body respectively, as single fractions, 1 week apart. Biochemical response (PSA) and pain relief (NRS-11) were recorded at 6 weeks post radiation. Baseline evaluations were done for all patients at presentation. Complete blood count was ordered before and after radiation to access hematological toxicity.

Results: At the end of 6 weeks all patients had variable pain relief. The average decline was 4 points on Numeric Rating Scale-11. Average NRS score was 8 before radiation treatment which declined to 4 after radiation. Mean PSA decline was 37%. 11 patients had grade I, and 3 patients had grade II hematological toxicity. All patients recovered without any complication.

Conclusions: Palliative hemi-body radiation offers good pain relief with reasonable biochemical control and acceptable toxicity.

2 The Prostate Cancer – Patient Empowerment Program reduces mental distress in men undergoing curative treatment: PC-PEP randomized trial

Gabriela Ilie*; Robert Rutledge *Dalhousie University, Halifax, Canada

Introduction & Objectives: While men with curative prostate cancer (PC) typically live disease-free for many years after treatment, they often experience treatment-related side-effects and poor mental health. Health-promotion strategies including aerobic training, strength and pelvic floor muscle exercises, meditation, dietary advice, intimacy and relationship education, and social support individually appear to improve mental health in PC survivors. However, to date no program combining all these mental health-promoting elements has been tested in a randomized trial. The aim of this study was to examine the effects of a six-month on-line home-based physical, mental, and social support intervention Prostate Cancer-Patient Empowerment Program (PC-PEP) on reducing non-specific psychological distress among menbeing treated with radical prostatectomy or curative radiotherapy (±hormone therapy).

Materials & Methods: This 12-month randomized clinical trial of 128 men (mean age=66.22 years) with biopsy-proven prostate adenocarcinoma (enrolled: December 2019-January 2022) was conducted at a tertiary care center in Halifax, Canada (clinician/ clinic referrals). Observers were blinded to patient randomization. Of 171 patients assessed for eligibility, 140 were randomized, and 128 remained eligible (were treated within 6 months). Patients scheduled to receive potential curative treatment for prostate cancer were randomized to either the on-line home-based PCPEP intervention (n=66) or a waitlist control group which received standard of care (n=62). Men in the PCPEP intervention received daily emails with video instructions for six months providing education and promoting physical, mental, and social activities. Activities included physical and pelvic floor exercises, relaxation, diet, intimacy, and social support education. Men had the option of calling two co-participants weekly and joining a monthly videoconference of all participants. The primary outcome was nonspecific psychological distress measured at baseline, 6 and 12 months using the Kessler Psychological Distress Scale (K10). The measure was assessed using total scores, as well as its binary cutoff (scores ≥20).

Results: The trial was completed by 128 patients (91.4%). Scores for psychological distress in the PC-PEP group and control group were statistically equivalent at baseline (M=15.18 and 15.58, respectively). At six months psychological distress in the PC-PEP group was significantly better than the control group (14.27 vs 17.70 respectively, p=.02) with participants in the control group having 3.35 (95%CI: 1.06-10.52) times higher odds of screening positive for clinical nonspecific psychological distress and need for treatment than men who received PC-PEP [3.59 (95%CI: 1.1611.07) at 12 months]. At one year the mental distress in PCPEP group continued to improve versus control group (M=12.25 and 17.43, respectively, p<0.001). Similar results emerged for the depression and anxiety subscales. Exit patient assessments highly endorsed PC-PEP (9.4/10).

Conclusions: PC-PEP significantly reduced the burden of psychological distress among men undergoing curative prostate cancer treatment. Multi-dimensional programming is needed to address the high levels of poor mental health in this population.

6 1

Figure 1. Effect of PC-PEP intervention on non-specific psychological distress, depression and anxiety subscales, and factors showing the specific makeup of a patient’s psychological distress (nervous, agitated, fatigue, and negative affect) from baseline to 6 months among 128 curative prostate cancer patients treated in Nova Scotia, Canada.

3

Figure 1. Effect of PC PEP intervention on non specific psychological distress, depression and anxiety subscales, and factors showing the specific makeup of a patient’s psychological distress (nervous, agitated, fatigue, and negative affect) from baseline to 6 months among 128 curative prostate cancer patients treated in Nova Scotia, Canada.

The dawn of the transperineal prostate biopsy

Mohammed El-Bahnasawi*; Ravisankar Gopakumara Pillai; Panagotis Christopoulos; Kayee Chow; Vijay Rammani; Vijay Sanger *Wythenshawe Hospital, Manchester, UK

psychological distress, depression and anxiety subscales, and factors showing the specific makeup of a patient’s negative affect) from baseline to 6 months among 128 curative prostate cancer patients treated in Nova Scotia, Canada.

Introduction & Objectives: The transperineal prostate biopsy is an accepted alternative to transrectal prostate biopsy in detection of prostate cancer. It is a safer alternative with lower complication rates. This was a retrospective audit to collect data on pre biopsy MRI characteristics, cancer detection rates, pain score and complication rates from patients who have undergone transperineal prostate biopsy under local anesthesia.

Materials & Methods: We set the standard as NICE guidelines for pre biopsy MRI, PROMIS trial for cancer detection rate, a national population-based study for complication rates, and another multi-centre study for comparing the pain score.

psychological distress, depression and anxiety subscales, and factors showing the specific makeup of a patient’s from baseline to 6 months among 128 curative prostate cancer patients treated in Nova Scotia, Canada.

Note: *p < 0.05. Standard error bars are shown. Covariates appearing in the model are evaluated at the following values: Covariates appearing in the model are evaluated at the following values: currently on prescribed medication for depression, anxiety or both at baseline = .1484, Charlson Comorbidities Index age adjusted at baseline = 2.5469, time between randomization and treatment (days) = 67.2734, treatment modality = 1.5156, relationship status at baseline = .9

Covariates appearing in the model are evaluated at the following values: Covariates appearing in the model are evaluated at for depression, anxiety or both at baseline = .1484, Charlson Comorb 67.2734, treatment modality = 1.5156, relationship status at baseline = .9

We collected retrospective data of all patients who had transperineal prostate biopsies from April 2020 to April 2021. In total, 211 patients had transperineal prostate biopsies during this period out of which 200 for diagnostic purposes and 11 were for active surveillance. All patients had pre biopsy MRI scans. All MRI scans were done using 3 Tesla scanners and dedicated specialist uro-radiologists reported all the scans. Radiologist evaluated the suspicious lesion using T2–weighted imaging, diffusion-weighted imaging and dynamic contrast enhanced MRI. The MRI prostate scans were reported as PIRADS 2,3,4 or 5. In the group of patients we assessed, 55 patients had a score of 2, 49 patients were scored as 3, another 49 patients with a score of 4 and 41 patients with a score of 5. The mean PSA was 10.4 (1 -163 ng/ml) and the mean prostate volume was 56 cc (15-210cc).

Results: Cancer detection rates were comparable with our transperineal biopsy throughout all PIRADS 2-5 groups to the PROMIS trial. Complication rates were lower than national rates at 0.5% admitted with sepsis, 0.5% with retention, 1% with haematuria. The average pain score was 2.9 which is lower than the accepted multi-center study pain score.

appearing in the model are evaluated at the following values: Covariates appearing in the model are evaluated at depression, anxiety or both at baseline = .1484, Charlson Comorbidities Index age adjusted at baseline = 2.5469, treatment modality = 1.5156, relationship status at baseline = .94

Conclusions: The transperineal prostate biopsy under local anaesthesia is a safe and effective alternative to transrectal prostate biopsy. Completely shifting to a transperineal route has given us a good cancer detection rate because it provides excellent sampling of the anterior region of the prostate as well as the apex, which is often under-sampled via transrectal approach. This route is also associated with low morbidity, particularly with low infectious complications.

4 Causes of death after prostate cancer diagnosis: a population-based study

Guo Yadong; Yao Xudong* *Shanghai Tenth People’s Hospital, School of Medicine, Tongji University, Shanghai, China

Introduction & Objectives: Mortality from noncancer causes in patients with prostate cancer (PCa) is unclear. This study assesses the causes and risks of noncancer death with each follow-up time period after PCa diagnosis.

Materials & Methods: Data from the Surveillance, Epidemiology, and End Results (SEER) program were analyzed for noncancer causes of death in PCa patients from 2000 to 2016. The standard mortality ratio (SMR) was calculated for noncancer mortality.

Results: Altogether, 752,352 patients with PCa were identified, and 180,862 (24.0%) died during follow-up. The largest proportion of deaths from noncancer causes (36%) occurred within 5 to 10 years after diagnosis. The most common causes of noncancer death are cardiovascular and cerebrovascular diseases and chronic obstructive pulmonary disease (COPD). Compared with the general age-matched male population, patients with PCa had a higher risk of death from any noncancer cause within 5 years, in particular other infectious diseases and suicide and self-inflicted injury. However, the risk of death from noncancer causes of PCa for more than 5 years is lower, except for Alzheimer’s disease and hypertension from 5 to 10 years after diagnosis. In addition, the risk of death from noncancer causes was influenced by treatment, ethnicity, and staging differences. In particular, compared with the general population, many noncancer causes of death have higher risk of death in patients with or without treatment within 1 to 5 years after diagnosis, whereas patients undergoing radical prostatectomy (RP) with or without radiotherapy (RT) or chemotherapy (CTx) are not at high risk of death from COPD, pneumonia and influenza, nephritis, nephrotic syndrome and nephrosis, septicemia, and atherosclerosis.

Conclusions: The risk of death from noncancer causes gradually decreased in all patients with PCa during each follow-up period after diagnosis In addition, the risk of dying from noncancer causes are influenced by differences in stage, ethnicity, and treatment. In particular, patients undergoing RP±RT/CTx and RT/CTx have a lower risk of death compared to the general population. These findings provide important implications for the healthcare management of patients with PCa.

Delphi study to identify consensus on patient selection for hydrogel rectal spacer use during radiation therapy for prostate cancer in the UK

Heather Ann Payne; Suneil Jain; Clive Peedell; Albert Edwards; James Andrew Thomas*; Prantik Das; Amanda Hansson Hedblom; Emily Woodward; Rhodri Saunders; Amit Bahl *Princess of Wales Hospital, Bridgend, UK

Introduction & Objectives: To identify consensus on patient prioritisation for rectal hydrogel spacer use during radiation therapy for the treatment of prostate cancer in the UK.

Materials & Methods: Delphi study consisting of two rounds of online questionnaires, two virtual advisory board meetings and a final online questionnaire. Setting: Radical radiation therapy for localised and locally advanced prostate cancer in the UK. Participants: Six leading clinical oncologists and one urologist from across the UK. Interventions: Rectal hydrogel spacer. Primary & Secondary outcome measures: None reported.

Results: The panel reached consensus on the importance of minimising toxicity for treatments with curative intent and that even low-grade toxicity-related adverse events can significantly impact quality of life. There was agreement that despite meeting rectal dose constraints, too many patients experience rectal toxicity and that rectal hydrogel spacers in eligible patients significantly reduces toxicity-related adverse events. However, as a consequence of funding limitations, patients need to be prioritised for spacer use. A higher benefit of spacers can be expected in patients on anticoagulation and in patients with diabetes or inflammatory bowel disease, but consensus could not be reached regarding patient groups expected to benefit less. While radiation therapy regimen is not a main factor determining prioritisation, higher benefit is expected in ultrahypofractionated regimens.

Conclusions: There is a strong and general agreement that all patients with prostate cancer undergoing radical radiation therapy have the potential to benefit from hydrogel spacers. Currently, not all patients who could potentially benefit can access hydrogel spacers, and access is unequal. Implementation of the consensus recommendations would likely help prioritise and equalise access to rectal spacers for patients in the UK.

6 25-years of incidence and survival of prostate cancer: results of SouthEuropean population-based cancer registry

Rafael Fuentes-Raspall*; Xavier Farré; Bernat Serdà-Ferrer; Arantza Sanvisens-Bergé; Montse Puigdemont-Guinart; Alicia Baltasar-Bagué; Carme Auñón-Sanz; Àlvar Roselló-Serrano; Arantxa Eraso-Urien; Rafael Marcos-Gragera *Catalan Institute of Oncology, The Girona Biomedical Research Institute , Girona, Spain

Introduction & Objectives: Despite a subjective perception among the scientific community that incidence of prostate cancer (PC) has been increasing along the last decades, data from population-based registries are moving in the opposite direction. We present the data of a Population-based Cancer Registry.

Materials & Methods: Population-based study of PC collected in the Girona Cancer Registry (GCR) between 1994-2018. Ageadjusted incidence and mortality rates calculated according to the 2013 European standard population (ASRE) per 100.000 menyear. Joint-point regression models were used for trend analysis, calculating the annual percentage changes (APC). Kaplan-Meier and Pohar-Perme estimates were used to analyze observed and net survival, respectively.

Results: A total of 9.846 cases of PC were registered between 1994-2018. The ASRE was 154.7 (95%CI:151.7;157.8) and the ageadjusted mortality rate was 38.9 (95%CI:37.3;40.6). The jointpoint analyses for trends, show an increasing incidence from 1994 to 2003 of 6.2% (95%CI: 4.4;8.1, p<0.001) but a decrease of -2.7 (95%CI: -1.9; -3.5, p<0.001) from 2003 until 2018. The APC related to mortality rates was -2.65 (95%CI: -3.3; -2, p<0.001).

Ten-years observed and net survival were 51.7% (95%CI: 50.6;52.9) and 76.7% (95%CI: 74.3;78.9), respectively. Net survival according to time of diagnosis has increased overtime showing 59.8% (1994-1998), 74.2% (1999-2003), 79.9% (2004-2008), and 85.1% (2009-2013).

Conclusions: Our analyses show a clear reduction in the prostate cancer incidence rates from 2003 onwards along with an increasing overall survival comparing the previous period to the more recent years.

Expected level of late (after 3 months) rectal toxicity in patients with and without hydrogel spacer

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Targeting BRD9 and PIM in prostate cancer

Thiara Rupasinghe*; Susan Heavey; Uzoamaka Okoli *University College London, London, UK

Introduction & Objectives: After local therapy for prostate cancer (PCa), 20-30% of patients will suffer from relapse and require systemic therapies such as targeted therapeutics. However, resistance to existing therapeutics requires development of new therapies. BRD9 has been identified as a potential therapeutic target in PCa meanwhile PIM inhibitors have been studied in pre-clinical and clinical stages in PCa. Limited success in trials due to toxicity issues warrants a new approach. PIM and BRD9 mRNA expression have been found to be significantly positively correlated (p<0.05). So, the aim of this study is to investigate the individual effects of I-BRD9, a BRD9 inhibitor, and PIM447, a PIM 1, 2 and 3 inhibitor, in PCa and assess them in combination. The use of patient-derived explants (PDEs) to investigate targeted therapeutics in the future, with potential to make pre-clinical cancer models more representatve, will also be assessed.

Figures

Materials & Methods: Publicly available data was analysed to investigate correlation between inhibitor gene targets. LNCaP cells, representative of aggressive prostate cancer, were treated with I-BRD9 and PIM447 and an endpoint assay was achieved using LIVE/DEAD and Proliferation staining. Spatial transcriptomics data from SCREEN study was used to investigate 3D patient explants, as a representative cancer model.

Results: Inhibitor gene targets PIM1, PIM2, PIM3 and BRD9 are positively correlated in PCa (p<0.05). PIM447 (IC50=1054nM) and I-BRD9 (IC50=147nM) significantly reduce LNCaP confluence relative to control (p<0.05), supported through live/dead and proliferation assays (Figure 1). Their combination effect is antagonistic (CI=1.06) (Figure 2). There is no significant difference in gene target expression between uncultured and cultured PDEs (p>0.05).

Conclusions: PIM447 and I-BRD9 show promise as targeted therapies in PCa. There is insufficient evidence in this study to support further investigation of these inhibitors in combination. 3D models of PDEs may be a viable option for future investigations of the individual inhibitors.

Figure 1. Figure 1a. Proliferation Assay Figure 1b. Live Dead Assay

Fluorescence Intensity (a.u.)

0 5 10 15

Drug treatment [nM] (a.u.)

Figures

Figure 1. Figure 1a. Proliferation Assay

Fluorescence Intensity (a.u.)

Control I-BRD9 PIM447

Fluorescence Intensity (a.u.)

Drug treatment [nM]

Control I-BRD9 PIM447 5

Proliferation assay of I BRD9, PIM447, their combination and control. P values were calculated through MMRM analysis with significance stated as P<0.05. There is significantly lower proliferation for each of the drug treated samples compared to control (p<0.05). Through Bonferroni, p<0.05 for every comparison except for I BRD9 vs Control and I BRD9+PIM447 vs PIM447 Created using GraphPad PRISM.

Proliferation assay of I BRD9, PIM447, their combination and control P values were calculated through MMRM analysis with significance stated as P<0.05. There is significantly lower proliferation for each of the drug treated samples compared to control (p<0.05). Through Bonferroni, p<0.05 for every comparison except for I BRD9 vs Control and I BRD9+PIM447 vs PIM447 Created using GraphPad PRISM.

Fluorescence Intensity (a.u.) *p<0.05

0 50 100 150

* Figures

Figure 1b. Live Dead Assay

IC50 Live Dead *p<0.05

Fluorescence Intensity (a.u.) Dead

Drug treatment [nM]

ControlI-BRD9PIM447I-BRD9+PIM447

Drug treatment [nM]

Proliferation assay of I-BRD9, PIM447, their combination and control. P-values were calculated through MMRM analysis with significance stated as P<0.05. There is significantly lower proliferation for each of the drug treated samples compared to control (p<0.05). Through Bonferroni, p<0.05 for every comparison except for I-BRD9 vs Control and IBRD9+ PIM447 vs PIM447. Created using GraphPad PRISM.

Normalised column graph of live dead assay of control, I BRD9, PIM447, combination treatment. P values were calculated using unpaired two tailed t tests with each drug compared to control. At the IC50, there is significantly more dead cell fluorescence with all three drug treatments compared to control (p<0.05). Created using GraphPad PRISM.

Drug treatment [nM]

Normalised column graph of live dead assay of control, I BRD9, PIM447, combination treatment P values were calculated using unpaired two tailed t tests with each drug compared to control. At the IC50, there is significantly more dead cell fluorescence with all three drug treatments compared to control (p<0.05). Created using GraphPad PRISM.

Normalised column graph of live-dead assay of control, I-BRD9, PIM447, combination treatment. P-values were calculated using unpaired two-tailed t-tests with each drug compared to control. At the IC50, there is significantly more dead cell fluorescence with all three drug treatments compared to control (p<0.05). Created using GraphPad PRISM.

Figure 2. Chou Talalay Combination Effect

Chou-talalay drug combination analysis. Fa is defined as percentage cell confluence with 1 indicating 100% confluence. A summary table showing CI values for each confluence interval with CI switching from synergistic to antagonistic above 25% confluence. Created using Microsoft PowerPoint.

Chou talalay drug combination analysis Fa is defined as percentage cell confluence with 1 indicating 100% confluence A summary table showing CI values for each confluence interval with CI switching from synergistic to antagonistic above 25% confluence. Created using Microsoft PowerPoint

Chou talalay drug combination analysis. Fa is defined as percentage cell confluence with 1 indicating 100% confluence A summary table showing CI values for each confluence interval with CI switching from synergistic to antagonistic above 25% confluence. Created using Microsoft PowerPoint

Figure 1. Figure 1a. Proliferation Assay Figure 1b. Live Dead Assay

10 7

Control I-BRD9 PIM447 I-BRD9+PIM447 0 5 10 15 IC50

Fluorescence Intensity

*p<0.05 * * * ControlI-BRD9PIM447I-BRD9+PIM447 0 50 100 150

* *

I-BRD9+PIM447 0

10 15 IC50

*p<0.05 * * *

50 100 150

IC50 Live

*p<0.05 * * *

I-BRD9+PIM447

IC50

*p<0.05 * * * ControlI-BRD9PIM447I-BRD9+PIM447

IC50 Live Dead

* * *

Lorenzo Bianchi* *IRCCS Azienda Ospedaliero-universitaria di Bologna, University of Bologna, Bologna, Italy

Introduction & Objectives: Accurate staging of biochemical recurrence (BCR) after radical prostatectomy (RP) for prostate cancer (Pca) is crucial to guide salvage therapies, including the promising metastases direct treatments (MDT); thus, PSMA PET/CT has been included in the EAU guidelines for its high diagnostic accuracy. The objective of this study is to evaluate the effect of MDT based on PSMA PET/CT on oncologic outcomes in oligorecurrent PCa patients.

Materials & Methods: We retrospectively evaluated 324 recurrent PCa patients after RP performed at three high-volume European centers between January 1998 and January 2021. Patients underwent PSMA PET/CT for restaging proposal after biochemical recurrence (BCR). We selected 176 (54.3%) Pca patients with positive PSMA PET/CT for oligorecurrent disease (≤3 lesions), which were stratified in two groups: group 1 (n=126), patients underwent MDT (including salvage lymphadenectomy [sLND], stereotactic body radiotherapy [SBRT] targeted to nodal or skeletal lesions, or a combination of sLND and SBRT); group 2 (n=50), patients underwent observation or androgen deprivation therapy (ADT) or salvage radiotherapy or combined treatment. Kaplan-Meier (KM) curves were plotted to evaluate differences between the two groups in terms of progression-free survival (PFS), radiologic PFS (rPFS), metastases free survival (MFS) and castration resistant prostate cancer free survival (CRPC-FS).

Results: Based on PSMA PET/CT results in oligorecurrent Pca patients (n=176), site of recurrence were following: local (12.5%), pelvic lymph-nodes (37.5%), extra-pelvic lymph-nodes (18.8%), axial bones (14.2%), extra axial bones (14.2%) and visceral (14.2%). In group 1 (n=126) including patients referred to MDT, 39,7%, 19,8%, 39,1% and 2,4% of patients underwent sLND, SBRT to lymph nodes, SBRT to skeletal and sLND+SBRT to skeletal lesion, respectively. At median follow-up of 24 months, survival analyses at KM curves depicted comparable PFS (43 vs 46%) and rPFS (63 vs 50%; all p≥0.5) and significantly higher MFS (82 vs 61%) and CRPC-FS (96 vs 84%) for patients treated with MDT compared to patients underwent observation, ADT or salvage radiotherapy (all p≤0.02).

Conclusions: PSMA-targeted treatments in oligorecurrent PCa after RP is an attractive approach to guide salvage treatments aimed to improve local control of disease. MDT guided by PSMA PET/CT seems to improve metastases progression and reduce the evolution to CRPC.

Does metastases-direct therapy guided by PSMA PET/CT really improve oncologic outcomes in oligorecurrent prostate cancer patients?

11 8

Lorenzo Bianchi* *IRCCS Azienda Ospedaliero-universitaria di Bologna, University of Bologna, Bologna, Italy

Introduction & Objectives: PSMA PET/CT is currently the best tool for staging prostate cancer (PCa) patients after radical treatments due to higher diagnostic accuracy compared to conventional imaging, turning it into a promising guide for PSMAtargeted treatments. The objective of this study is to evaluate the oncological outcomes of recurrent PCa patients according to PSMA PET/CT results.

Materials & Methods: We retrospectively evaluated 324 recurrent PCa patients after radical prostatectomy performed at three high-volume European centers between January 1998 and January 2021. Patients underwent PSMA PET/CT for restaging proposal after biochemical recurrence (BCR) and were stratified in two groups according to PSMA PET/CT results (positive vs negative). Patients with positive PSMA PET/CT for oligometastatic (≤ 3 lesions) underwent PSMA-targeted salvage treatment. Patients with positive PSMA PET/CT for polimetastatic (>3 lesions) underwent systemic therapy. Patients with negative PSMA PET/ CT were treated with non-imaging guided salvage therapy. Kaplan-Meier (KM) curves were plotted to evaluate differences in progression-free survival (PFS), radiologic PFS (rPFS), metastases free survival (MFS) and castration resistant prostate cancer free survival (CRPC-FS). Multivariate Cox regressions were performed to identify independent predictors of PFS and rPFS.

Results: Overall, 193 patients (group 1) and 131 patients (group 2) had positive and negative PSMA PET/CT, respectively. Patients in group 1 had higher pT≥3, pN1, ISUP≥4 and PSA at PSMA PET/ CT (0.7 vs 0.4) compared to patients in group 2 (all p≤0.03). After salvage treatments, no significant differences were recorded in terms of further clinic recurrence sites, PSA at BCR, time to BCR, overall mortality and cancer specific mortality. At median follow-up of 23 months, survival analyses at KM curves depicted significantly lower PFS (53 vs 80%), rPFS (62 vs 89%), MFS (77 vs 94%) and CRPCFS (91 vs 97%) for patients in group 1 compared to patients in group 2 (all p≤0.006). At multivariate Cox regression, positive PSMA PET/CT (HR=2), patients’ age (HR=0.97) and pT≥3b (HR=1.84) were independent predictors of PFS (all p≤0.02); positive PSMA PET/CT (HR 2.64) and patients’ age (HR=0.95) were independent predictors of rPFS (all p≤0.002).

Conclusions: Patients with positive PSMA PET/CT had worse oncologic outcomes in terms of PFS, rPFS, MFS and onset of CRPC status compared to men with negative PSMA PET/CT. Thus, PSMA PET/CT for restaging PCa still have an important role for patients’ prognosis counseling and salvage treatment plan.

The impact of PSMA PET/CT on oncologic outcomes of patients with recurrent prostate cancer: the experience of 3 high-volume European centers

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Immunohistochemical PSMA expression and histology predictors

Alessandro Pissavini*; Lorenzo Bianchi; Luigia Vetrone; Riccardo Mei; Andrea Farolfi; Francesca Giunchi; Alessio de Giovanni; Letizia Calderoni; Francesca Serani; Francesco Costa; Matteo Droghetti; Riccardo Schiavina; Eugenio Brunocilla; Paolo Castellucci; Stefano Fanti *IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy

Introduction & Objectives: PSMA-PET/CT is used in clinical practice for staging and restaging prostate cancer (PCa). Still, there are cases in which there is no significative PSMA uptake despite high PSA levels, highlighting the need to identify histology and immunohistochemistry (IHC) features that might influence PSMA uptake and to improve the patients eligible for a PSMA-PET study. The aim of this study was to assess the correlation among histology, IHC and PSMA-PET parameters in a cohort of high-risk prostate cancer (PCa) patients at presentation.

Materials & Methods: This is a single-center, prospective observational cohort study in high-risk PCa patients enrolled in the PSMA-PROSTATA registry study. Patients candidate to surgery received PSMA-PET/CT for primary staging. Age, iPSAlevel, Gleason score, ISUP grade, histologic pattern, presence of lymph-vascular invasion (LVI), PSMA-IHC visual quantification (VS) with four-tiered system (0=negative, 1+=weak, 2+=moderate, 3+=strong), PSMA-IHC growth pattern (infiltrative vs expansive) were collected both for biopsy and primary prostatic lesion (T) histology and compared with results from PSMA-PET/CT (positive/negative according to PROMISE criteria, SUVmax, PSMA tumour volume [PSMA-TV] and total lesion [PSMA-TL]).

Results: Overall, 14 patients were analysed, mean age was 66; median iPSA was 6.4 ng/dL (range 3.3-44.5). PSMA-IHC at biopsy showed strong PSMA expression (VS 3+) in 8 patients, and PSMA-ICH at radical prostatectomy (RP) specimen showed strong PSMA expression (VS3+) in 10 patients, of which 7 with fused cell type and 3 with cribriform type. After RP, we found a correlation between biopsy and T histology pattern and PSMAIHC: 80% of patients with high PSMA expression (VS 3+) in RP specimens has high PSMA expression (VS3+) at bioptic cores (p=0.2 at McNaemar test). ISUP grade of 5, 4, 3 and 2 was found in 5, 5, 3 and 1 patients, respectively. PSMA-PET/CT detection rate for T was 100%. We found also correlation between high PSMATV/TL-PSMA and cribriform T histology pattern at Kruskal-Wallis analysis (p<0.05). PSMA infiltrative growth pattern vs expansive was also correlated with higher PCa SUVmax (p=0.034). Moreover, high PSMA-TV and TL-PSMA were shown to be correlated with LVI (p<0.05). Histology found N metastasis in 6 patients, with PSMA expression at IHC of 3+ and 1+ in 5 and 1 patients, respectively; however, only 1 patient has a positive PSMA-PET for N metastasis and another 1 turned false positive.

Conclusions: This preliminary study demonstrated a possible correlation among PSMA-IHC, histology pattern and PSMA-PET/ CT for T evaluation. An intense PSMA-PET uptake could be able to predict tumour aggressiveness. We observed an intra-patient heterogeneity between IHC and PSMA expression on primary tumour and on N metastasis, and a correlation of IHC findings between prostate biopsy and pathologic specimens.

Rick Hermsen; Esmée Wedick; Maarten Vinken; Ludwike van Kalmthout; Heidi KüstersVandevelde; Charlotte Wijers; Diederik M. Somford; Jean-Paul van Basten* *Canisius Wilhelmina Hospital, Nijmegen, The Netherlands

Introduction & Objectives: Treatment options and prognosis of patients with PCa strongly depend on presence of metastases, which are predominantly located in skeleton and lymph nodes. Extended pelvic lymph node dissection (ePLND) is recommended by the European Association of Urology (EAU) guidelines as most accurate method for lymph node staging when the risk of LNI exceeds five per cent on the prevailing nomograms. But ePLND is invasive and bears risk of complications. Considering the risk and expenses of surgery for diagnostic purpose, research is focusing on noninvasive diagnostic imaging techniques for lymph node staging.

Fluorine-18 (18F) prostate specific membrane antigen (PSMA) 1007 (18F-PSMA-1007) is a radiotracer used in prostate cancer (PCa) staging.

Objective was to determine diagnostic accuracy of 18F-PSMA-1007 PET/CT compared to histopathological results of extended pelvic lymph node dissection (ePLND) in men with intermediate or high-risk PCa. Results were compared with two recent Dutch prospective studies with 68Ga-PSMA PET/CT (PEPPER-trial) and 18F-DCFPyl PET/CT (SALT-trial).

Materials & Methods: Men with newly biopsy confirmed intermediate or high-risk PCa were prospectively enrolled in the Molecular Imaging 18F-PSMA-1007 PET/CT for lymph Node sTaging in primary PCa (MINT) trial from February 8th, 2019 until June 9th, 2021.18F-PSMA-1007 PET/CT images were separately reviewed by two experienced nuclear medicine physicians. Lymph nodes were visually assessed and based on a 5-point Likert scale score (benign, probably benign, indecisive, probably malign, malign) within their anatomical template. A score of ≥4 was considered ‘positive’. In case of discrepancies, a consensus read was done with the two nuclear medicine physicians. Diagnostic accuracy was evaluated by histopathology of template resections. Sensitivity, specificity, positive and negative predictive values (PPV, NPV) for LNI detection of 18F-PSMA-1007 PET/CT were calculated.

Results: Ninety-nine men were evaluated, 30.3% showed histologically confirmed LNI. Median number of resected nodes was 22 (IQR 17-28). Patient based sensitivity, specificity, PPV and NPV were 53.3% (95% CI 34.3-71.7%), 89.9% (95% CI 80.295.8%), 69.6% (95% CI 51.2-83.3%) and 81.6% (95% CI 75.0-86.8%), respectively. Template based sensitivity was 12.9% (95% CI 5.723.9%), specificity 97.7% (95% CI 96.6-98.5%), PPV 23.5% (95% CI 12.7-39.5%) and NPV 95.3% (95% CI 94.9-95.7%).

in primary staging high-risk prostate cancer patients studied with PSMA PET/CT: a PSMA expression investigation

11

Lymph node staging with fluorine-18 prostate specific membrane antigen 1007-positron emission tomography/computed tomography in newly diagnosed intermediate to high risk prostate cancer using histopathological evaluation of extended pelvic node dissection as reference

13 10

Conclusions: 18F-PSMA-1007 PET/CT showed high specificity but moderate to low sensitivity for LNI detection in intermediate and high risk PCa. Template-based analysis showed lower results compared to PEPPER- and SALT trials probably due to templates in our study being more precise and therefore prone to error. However, a side-based analysis showed results more in line with comparable trials. The 18F-PSMA-1007 PET/CTunderestimates the burden of pelvic metastasis and therefore cannot replace ePLND as primary staging procedure in men with intermediate to high risk prostate cancer.

12 The role of viral factors in prostate cancer onset and progression

Anita Ognqnova Kavrakova*; Elena Ivanova Todorova; Bilyana Georgieva; Kremena Mesechkova; Krassimir Yanev; Georgi Ivanov; Goran Derimachkovski; Vanyo Mitev; Albena Todorova

*Medical University of Sofia, Genica, Sofia, Bulgaria

Introduction & Objectives: Тhe aim of the study was to investigate the potential association of viruses from the Herpesviridae family (HHVs) and Human Papilloma viruses (HPVs) with the onset and progression of prostate cancer (PCa).

We present new evidences supporting our hypothesis by findings of persistent active infection and tumorogenic biological activity in Bulgarian patients with PCa, benign prostatic hyperplasia (BPH) and PCa/BPH.

Materials & Methods: “Tru-cut” biopsies from 78 patients- 58 with PCa and 20 with BPH were analyzed. DNA extractions, PCR, Real-Time PCR, PCR-based hybridization method were applied.

Results: HPVs were detected in 9% of PCa “tru-cut” biopsies: lowrisk HPVs 42, 54/55; high-risk HPVs 18, 51. Histological examination showed a presence of acinar adenocarcinoma in combination with benign prostatic hyperplasia (BPH), PIN and inflammation.

Active viral infection with the following four members of the HHV family CMV, EBV, HHV-6 and HHV-7 were detected in 11,5% of the patients.

Most of the cases with active infection with HHVs fall in the clinical group of patients with BPH (25%) and only 6,9% of the patients with PCa.

We discovered mass morpho-histological findings for an inflammatory process: atypical, atrophic and precancerous changes, chronic inflammatory infiltration, amyloid bodies and cytopathic effect, typical for most of the detected viruses, mainly EBV, CMV, HHV-6, concentrated in the BPH patients group. Similar morpho-histological picture and positive molecular results for HHVs in over 25% of the BPH and BPH/PCa patients, with PSA values in the gray area, characterizes a critical phase of PCa development and a high risk of causing malignancy by virusassociated tumorigenic process.

Conclusions: Our observations support the theory of "hit and run" model of PCa- HHVs and HPVs are much more active in the initial and critical stages, by triggering the disease and are less commonly detected in the advanced phase of the disease. Our results suggest that long-term active HHVs/HPV infection contributes to intraprostatic inflammation, precancerous lesions and BPH, and later to malignancy of the prostatic epithelium. The prevention and treatment of prostate viral infections could be with a positive effect even on the control of PCa frequency.

Grants: D-84/04.06.2021, Medical University-Sofia, Bulgaria.

Table. Time to CRPC by ARASENS stratification subgroups

Stratification subgroup* Study arm (patients)

Extent of disease

Time to CRPC, median (95% CI), months HR (95% CI)†

M1b DARO (n=517) NE (NE, NE) 0.35 (0.29, 0.43) PBO (n=520) 19.1 (16.4, 21.8)

M1c DARO (n=111) 35.9 (30.4, NE) 0.48 (0.33, 0.69)

PBO (n=118) 16.6 (12.6, 24.7)

Bertrand Tombal*; Maha Hussain; Fred Saad; Karim Fizazi; Cora N. Sternberg; E. David Crawford; Evgeny Kopyltsov; Arash Rezazadeh Kalebasty; Boris Alekseev; Álvaro Montesa Pino; Dingwei Ye; Francis Parnis; Felipe Melo Cruz; Teuvo L.J. Tammela; Hiroyoshi Suzuki; Heikki Tuomas Joensuu; Silke Thiele; Rui Li; Iris Kuss *Cliniques Universitaires Saint Luc, Brussels, Belgium

Introduction & Objectives: In ARASENS (NCT02799602), darolutamide added to a current standard of care, androgendeprivation therapy (ADT) + docetaxel, significantly reduced the risk of death by 32.5% (hazard ratio [HR] 0.68; 95% confidence interval [CI] 0.57, 0.80; P<0.0001) vs placebo + ADT + docetaxel in patients with metastatic hormone-sensitive prostate cancer (mHSPC). Extent of metastatic spread and alkaline phosphatase (ALP) are known prognostic factors in mHSPC. We investigated whether darolutamide in combination with ADT + docetaxel would increase overall survival (OS) in prespecified ARASENS stratification subgroups based on extent of disease and ALP.

Materials & Methods: Patients were randomized 1:1 to receive darolutamide 600 mg or matching placebo twice daily in combination with standard ADT + docetaxel. Randomization was stratified by metastatic spread according to TNM classification (nonregional lymph node metastases only [M1a]; bone ± lymph node metastases [M1b]; visceral ± lymph node/bone metastases [M1c]) and ALP value (< or ≥ upper limit of normal [ULN] at study entry). OS was the primary endpoint. Time to castration-resistant prostate cancer (CRPC) and safety were key secondary endpoints.

Results: Between November 2016 and June 2018, 1306 patients were randomized to receive darolutamide (n=651) or placebo (n=655), of whom 1305 patients (darolutamide n=651, placebo n=654) were included in the full analysis set. By extent of disease, 3.0% of patients had M1a (not analyzed further), 79.5% had bone metastases (M1b), and 17.5% had visceral metastases (M1c). In the ALP subgroups, 44.5% and 55.5% had ALP < and ≥ ULN, respectively. Baseline characteristics were generally balanced between arms in all stratification subgroups. The primary data cut-off date was October 25, 2021. All subgroups showed consistently favorable OS benefits of darolutamide vs placebo, with stratified HRs (95% CIs) of 0.66 (0.54, 0.80) for M1b and 0.76 (0.53, 1.10) for M1c, and 0.65 (0.47, 0.89) for ALP < ULN and 0.69 (0.56, 0.85) for ALP ≥ ULN. The significant benefit of darolutamide vs placebo in delaying time to CRPC in the overall population (HR 0.36; 95% CI 0.30, 0.42; P<0.001) was also consistently seen across stratification subgroups (Table). In the overall population, rates of any-grade, grade 3–5, and serious adverse events (AEs) were similar in the two study arms. The incidences of the most common treatment-emergent AEs (≥10%), the majority of which are known docetaxel-related AEs, were highest during the overlapping docetaxel treatment period in both arms.

Conclusions: In patients with mHSPC, addition of darolutamide to ADT + docetaxel significantly increased OS and delayed time to CRPC vs ADT + docetaxel alone. Consistent OS benefits were observed in prespecified stratification subgroup analyses based on extent of disease (bone or visceral metastases) and ALP (< or ≥ ULN). AE rates were similar in both arms.

ALP

< ULN DARO (n=290) NE (NE, NE) 0.28 (0.21, 0.37)

PBO (n=291) 24.8 (22.1, 27.8)

≥ ULN DARO (n=361) 41.5 (27.8, NE) 0.42 (0.35, 0.52) PBO (n=363) 14.0 (13.6, 16.5)

*M1a subgroup not shown, because of small patient numbers. †HRs and 95% CIs are based on Cox regression model stratified by ALP (< vs ≥ ULN) for extent of disease stratification subgroups and by extent of disease (M1a vs M1b vs M1c) for ALP stratification subgroups. ADT, androgen-deprivation therapy; ALP, alkaline phosphatase; CI, confidence interval; CRPC, castration-resistant prostate cancer; DARO, darolutamide + ADT + docetaxel; HR, hazard ratio; M1a, nonregional lymph node metastases only; M1b, bone ± lymph node metastases; M1c, visceral ± lymph node/bone metastases; NE, not estimable; PBO, placebo + ADT + docetaxel; ULN, upper limit of normal.

Stratification subgroup analysis of overall survival with darolutamide versus placebo in combination with androgen-deprivation therapy and docetaxel in the phase 3 ARASENS trial

15 13

Almudena Monllor Méndez*; Marta Jiménez Navarro; Alicia Díaz Silvan; Sara González Nieto; Lara Torres León; Raquel Clemente Graffigna; Angelo Jesus Sotillo; Lorena García; Jesús Monllor Gisbert

*Hospital Universitario Nuestra Señora de Candelaria, Tenerife, Spain

Introduction & Objectives: Prostate cancer (PC) is the second most frequent type of cancer in men and the fifth most common cause of cancer-related death in men. MRI and different PET radiotracers have been used to improve the accuracy of conventional imaging techniques currently used in PC diagnosis proccedure. One of those is PSMA PET/CT. PSMA is overexpressed in most PC cells and is associated with higher PSA values at diagnosis, as well as with a worse overall survival.

The main objective in this study is to analyze the positive PSMA PET TC result - related conditions in patients diagnosed with biochemical recurrence (BR) of PC at our Institution.

Materials & Methods: This retrospective, single-center study was conducted in our Urology Department of H.U.N.S.C , Tenerife, Spain.

We analyzed the medical records of 32 patients diagnosed with BR of PC who consecutively underwent PSMA PET TC at our institution between March 2022 to June 2022. All patients underwent PSMA PET TC using 18F - labeled PSMA radiotracers.

Based on abnormal uptake, lesions were divided into 3 groups: prostate gland or prostate bed, lymph nodes and bone lessions.

Statistical analysis was performed with SPSS, version 25 (IBM).

Results: Patients age median was 67,41. 90,6% of patients underwent surgery, while only 9,4% of them received radiotherapy as first treatment.

PSA level median before the realization of PSMA PET-TC was 1,88 ng/mL [0,2-15,5].

Cross sectional imaging techniques were also performed: CT (71,9%)(n=23), bone scintigraphy 65,6% (n=21), MRI 59,4% (n=19) and Choline PET TC 37,5% (n=12).

Of the 32 patients, 19 (59,4%) showed one or more areas suggestive of recurrent PC.

The detection efficacy of 18F - PSMA PET/CT correlated positively with PSA level and was 80% (7/13) for a PSA value of >2 ng/ mL, 60% (3/5) for a PSA value of 1 to 2 ng/mL, 83% (5/6) for a PSA value of 0.5 to 1 ng/mL, 53% (7/13) for a PSA value of 0.2 to 0.5 ng/mL.

Mean PSA level was significantly lower among patients with negative results on 18F PSMA PET/CT than among those with positive results.

Attending to abnormal uptake 21.1 % of them were found at prostate gland or prostate bed, 78,9% at lymph nodes and 26,3% correspond to bone lessions. Up to 38,7% of the patients should be considered oligometastatic , while 16,1% would be polimetastatic attending to Lecouvet criteria.

Conclusions: In conclusion, our study shows that PET-PSMA proved to be useful for the evaluation of BR in PC. It also appears to have higher sensitivity than other imaging modalities for detecting sites of recurrence, even at very low PSA values. This could eventually lead to change the treatment in these patients.

Figure 1 N (%)

18 F PSMA

No data 1 (3,1)

Negative 12 (37,5) Positive 19 (59,4)

Figure

18 F

Negative, n (%) Positive, n (%)

Low risk 2 (22,2) 3 (16,7)

Intermediate risk 0 2 (11,1)

High risk (localized) 3 (33,3) 2 (11,1)

High risk (locally advanced) 4 (44,4) 11 (61,1)

Conditions associated with the positivity of PSMA PET CT in the detection of tumour recurrence in patients with biochemical recurrence of prostate cancer

16 14

18 F PSMA PET TC results

PET TC, n(%)

2 18F PSMA PET TC results attending to PSA levels PSA 18 F PSMA PET TC Negative 18 F PSMA PET TC Positive <0 2 2 0 0 2 0 5 6 7 0 5 1 1 5 1 2 2 3 2 5 0 1 5 10 0 2 >10 1 1 Sum 12 19

3 18F PSMA PET TC results attending to D Amico s risk scale

PSMA PET TC

Adoption of active surveillance protocols for prostate cancer remains very low among urologists in Greece despite Covid-19 pandemic

Filippos Kapogiannis*; Konstantinos Fasoulakis; Panagiotis Papikinos; Vasileios Spapis; Aggelis Aggelopoulos *Hippokrateion General Hospital, Athens, Greece

Introduction & Objectives: Active surveillance (AS) is currently considered the preferred treatment strategy with a strong recommendation for patients with low-risk prostate cancer and an option for selected cases with intermediate-risk cancer. The proportion of men with low-risk cancer who are on AS varies substantially, both nationally and internationally. The aim of our study was to report the adoption of AS and possible factors affecting it, in a period of time that someone would expect an expansion of AS such as the recent Covid-19 pandemic.

Materials & Methods: Between June 2020 and June 2022 we conducted a cross-sectional study. It comprised of structured questionnaires and interviews with urologists using email addresses obtained from the Hellenic Urological Society membership directory and through social media. The questionnaire was constructed according to physicians' characteristics, acceptance and inclusion criteria, and attitudes on AS, and included dichotomous, multiple choice, and multiple answer questions. Incomplete questionnaires were discarded. To enhance recruitment and add to the existing knowledge we sent a leaflet to all participants which incorporated the EAU 2022 recommendations for AS and the recent DETECTIVE consensus statements regarding AS.

Results: A total of 110 questionnaires were completed and included in the analysis. 71 participants practiced urology in a national health system hospital, 5 in a university hospital, and 34 in the private sector. All urologists agreed that a potential candidate for AS should meet the D'Amico classification criteria for low-risk prostate cancer. However, only 2 actually proposed AS to their patients as the preferred treatment strategy. To investigate the reluctance to perform AS, urologists were asked about their reasons not to offer AS as a valid option. In the bivariate analysis, patient anxiety (p=0.021 and fear of urologists losing their patients (p=0.04) were significant predictors that prevented endorsement of AS. Moreover, there was a trend toward a lack of robust evidence in the literature (p=0.067) and the absence of a multidisciplinary service (p=0.056) that could attribute to existing distrust of AS. The discrepancy between urologists is intensified by the fact that 85% reported that they did not use a predefined surveillance protocol but would adapt their practice according to their own convenience and the patient's compliance.

Conclusions: This study demonstrated that AS rates in Greece remain proportionally very low -if not absent- even during the period of the Covid-19 pandemic, despite anticipation of a contrary effect. A further implementation of AS is hindered by various doctor-, patient-, or health care system-related limitations. Focus on efforts to expand knowledge among the urological community, continuous patient education and quality improvement of health services will eventually boost national awareness and compliance towards AS.

Hoda Abdel-Aty*; Nabil Hujairi; Iain Murray; Nicholas van As; Nicholas D. James *The Institute of Cancer Research, London, UK

Introduction & Objectives: PET/CT has improved accuracy over conventional imaging for staging prostate cancer. Limited data exists on the influence of PET/CT on management and clinical outcomes. The aims of the study are to determine the concordance between PET/CT and conventional imaging in PET/ CT-detected newly diagnosed metastatic prostate cancer and explore the patterns of PET/CT-directed treatment.

Materials & Methods: Men with PET/CT-detected newly diagnosed metastatic prostate cancer with baseline bone scintigraphy were reviewed retrospectively. Concordance between PET/CT and conventional imaging (low-dose CT of the PET/CT and bone scintigraphy) was defined by the same number of lesions detected per-patient for nodal, bone and visceral metastases. Patients were sub-grouped on PET/CT and conventional imaging into oligometastatic and polymetastatic disease. Oligometastases was defined as ≤5 metastases in the bone and/or non-regional lymph nodes. Sub-group concordance was the same sub-group assigned for each imaging modality. Patient and treatment characteristics at baseline were recorded.

Results: Between 2015 and 2021, 245/2152 (11%) patients had newly diagnosed metastatic prostate cancer on PET/CT. 74/245 (30%) patients with baseline bone scintigraphy were analysed. 54/74 (73%), 9/74 (12%) and 11/74 (15%) patients had baseline 68Ga-PSMA-11, 18F-PSMA-1007 and 18F-Choline PET/CT respectively. The median age was 69 (range 48-86) years. Tumour characteristics are summarised in Table 1. Concordance for nodal, bone and visceral metastases is summarised in figure 1. There was a 3-fold increase for bone metastases detection with PET/CT.

38/74 (51%) patients were PET-oligometastatic and 35/74 (47%) were PET-polymetastatic, with a median PSA of 33 (range 3.2-400) ng/mL, and 61 (range 4.8-5400) ng/mL respectively.

39/74 (53%) were oligometastatic on conventional imaging. Concordance was present in 20/39 (51%) patients. Of the remaining 19/39 (49%) patients, 10/19 (53%) were PETpolymetastatic with up to 10 lesions, and 6/19 (32%) were PETpolymetastatic with >10 lesions.

In the PET-polymetastatic subgroup, 16/35 (46%) had up to 10 lesions and 12/35 (34%) had >10 lesions. In patients with up to 10 lesions, 10/16 (62.5%) were oligometastatic, and 5/16 (31%) were non-metastatic on conventional imaging. In patients with > 10 lesions, 2/12 (17%) were polymetastatic, 6/12 (50%) were oligometastatic, and 4/12 (33%) were non-metastatic on conventional imaging. Figure 2 CONSORT diagram summarises the stage shift.

27/38 (71%) PET-oligometastatic patients received prostate radiotherapy (± pelvic lymph nodes, ± bone metastases). 18/35 (51%) PET-polymetastatic patients received prostate radiotherapy (± pelvic lymph nodes, ± bone metastases), all of which were “low-burden” disease on conventional imaging as defined by the CHAARTED criteria.

16

Concordance of positron emission tomography/computed tomography (PET/CT) with conventional imaging in PET/CT detected newly diagnosed metastatic prostate cancer

17 15

Conclusions: PET/CT detects more metastatic lesions than conventional imaging. The magnitude of effect with a “right stage shift” poses implications on treatment decisions and future trial recruitment. Work is on-going to expand the patient dataset to determine the patterns of response and relapse following PET/ CT-directed treatment.

Tumour characteristics N (%)

ISUP Grade Group

Non-histological diagnosis 4 (5)

Group 2 5 (7)

Group 3 11 (15)

Group 4 4 (5)

Group 5 50 (68)

MRI prostate N (%) PET/CT N (%)

T1N1 1 (1) T2N1 1 (1)

T2N0 3 (4) T2N0 2 (3)

T3N0 1 (1)

T3N0 26 (35) TxN0 1 (1)

T2N1 1 (1)

T3N0 16 (22)

T3N1 8 (11)

T3N1 27 (37) TxN0 1 (1)

T2N1 1 (1)

T3N1 23 (31)

T4N0 1 (1)

T4N1 1 (1)

T4N0 3 (4) T3N0 2 (3)

T4N1 1 (1)

T4N1 14 (19) T2N1 1 (1)

T3N1 7 (10) T4N1 6 (8)

Conventional imaging N (%) PET/CT N (%)

N0M0 13 (18) N0M1 5 (7)

N1M1 8 (11)

N0M1 28 (38) N0M1 17 (23)

N1M1 10 (14)

N1M0 1 (1)

N1M0 9 (12) N1M1 9 (12)

N1M1 24 (32) N0M1 2 (3)

N1M1 22 (29)

Figure 2. CONSORT diagram for subgroups on PET/CT with a right stage shift on conventional imaging.

Table 1. Tumour characteristics.

Figure 1. Venn diagram representing the number of patients with concordance between PET/CT versus CI for bone, lymph node and visceral metastases. a) Patients with bone metastases on PET/CT and CI. b) Patients with lymph node metastases on PET/CT and CI. c) Patients with visceral metastases on PET/CT and CI.

17 Bridging gap between pre and postoperative prostate biopsies: PI RADS correlation with final histopathological data

Tsitsi Abakelia*; Ketevan lashkhi; Sophio Kakhadze *Research Institute of Clinical Medicine, Tbilisi, Georgia

Introduction & Objectives: Prostate cancer (Pc) is the second most commonly diagnosed cancer in men population. In clinical practice treatment strategy and therefore survival outcome of Pc depends on histopathological grade of the tumor evaluated by Gleason scoring system. In the recent past transrectal ultrasound (TRUS) guided biopsy was most popular tool to derive Gleason score (Gs). However TRUS biopsy showed differences in Gs with prostatectomy specimens; moreover sextant biopsies undersample most prostates and may miss small index lesion, leading to the false negative results, which causes to late cancer detection and overly intensive treatment. Multiparametric magnetic resonance imaging (mpMRI) and MRI-targeted biopsy demonstrated potential to solve this problem, with high accuracy in prostate cancer diagnosis. At the time of primary diagnosis high diagnostic accuracy is crucial for an optimal Pc management. Preoperative prediction of Pc grade with high accuracy may modulate treatment strategy and therefore impact on cancer prognosis, especially in patients with indolent tumor, for whom potential risks of surgery outweights the survival benefit.

We aim to define strength of correlation between risk stratification scheme for mpMRI-Prostate Imaging Reporting and Data System (PI RADS) and final histopathological data-postoperative Gleason scores (Gs); apparent diffusion coefficient (ADC) and Gs; to define mean ADC values for each Gleason grade as well. To determine compliance of MRI data in preoperative prostate cancer grading with gold standard-morphological data.

Materials & Methods: 203 consecutive patients suspected for prostate cancer (Pc) on mpMRI examination who underwent subsequent preoperative TRUS or MRI/Ultrasound fusion guided biopsies were included to this study prospectively. 50 patients were excluded due to preoperative negative prostate biopsies, leaving 153 treatment-naive patients, with positive preoperative biopsies. Multiparametric MRI (mpMRI)s were interpreted utilizing PI RADS V.2.1; this data was correlated with histopathological findings. Concordance of preoperative and postoperative Gleason scores was evaluated as well.

Results: Relationship of PI RADS and Gleason scores was defined by Pearson’s correlation. It revealed high positive correlation of PI RADS sum scores and Gleason scores (r=0.646 and p=0.000.) high negative correlation was seen between apparent diffusion coefficient (ADC) and Gleason scores (r=-0.849 and p=0.000). Mean ADC values were calculated for each Gleason group. 18 patients out of 153 showed Gs upgrade from TRUS biopsies to prostatectomy specimens.

Conclusions: PI RADS sum score and Gleason grade demonstrated significantly high correlation for our patients. With apparent diffusion coefficient calculation PI RADS preoperatively can predict Gs noninvasively and this makes mpMRI valuable tool in preoperative prostate cancer grading, as it gives reliable data among pre and postoperative pathological reports providing an optimal treatment strategy.

203 consecutive patients suspicious for Prostate cancer on mpMRI were included in prospective study

Preoperative biopsies were derived by TRUS guided biopsy in 137 patients and MRI/Ultrasound fusion guided biopsy in 16 patients

50 patients were excluded due to the negative preoperative biopsies for Prostate cancer

153 patients with positive preoperative biopsies were included in the final analysis

Postoperative Gleason scores were derived from radical prostatectomy specimens

Gleason scores of preoperative biopsies were compared with prostatectomy specimens

Strength of correlation was defined between PI RADS scores and final histopathological data-postoperative Gleason scores

Figure 1. Flow chart of materials and methods. Figure 2. Box plot analysis of mean ADC values with regard to Gleason scores. Figure 3. Gleason score upgrade from TRUS biopsy to radical prostatectomy. Figure 4. Suspicious lesions (arrows) on mpMRI: 4 points on T2W for homogeneous hypointensity (a); 5 points on DWI for focal very low ADC (b,c); and 5 points on DCE-MRI for washout curve in a focal lesion (d); type 3 enhancement curve (e); sum-score of 14 points. Microgram-Gleason score 8(3+5) carcinoma (f).

Should we or should we not biopsy all PI-RADS 3 lesions?

A retrospective analysis

João Pina*; Thiago Andrade Guimarães; Hugo Pinheiro; Miguel Gil; Luís Campos Pinheiro *Centro Hospitalar Universitário de Lisboa Central, Lisbon, Portugal

Introduction & Objectives: Magnetic resonance imaging/ ultrasound fusion guided biopsy (MRI/US-FB) have changed the paradigm of PCa diagnosis by selecting the target-lesion. Suspicious lesions assessed by mpMRI are classified according to the likelihood of being a csPCa based on PI-RADS v2.1. Each lesion is assigned a score from 1 to 5. Equivocal lesion is assigned as PIRADS 3. Here, we aim to provide parameters that can be useful in deciding whether or not to biopsy PI-RADS 3 lesions.

Materials & Methods: We retrospectively analyzed a confidential database of patients with PI-RADS 3 lesions subjected to MRI/US-FB between October 2020 and April 2022.Baseline characteristics of patients and pathological outcomes were compares using Student-t-test (age, PSA, PSAD, prostatic volume (PV) and lesion size, total of cylinders collected and percentage of positive cylinders). Chi-square test was used for categorical data (peripheric lesion; multifocality; biopsy-naïve; presence of PCa; neural invasion; lymph vascular invasion; cribriform pattern; intraductal pattern and EPE. A _P_- value < 0,05 was considered statistically significant. Those statistical analysis was performed using SPSS v.25 (IBM SPSS Statistics for macOS, Version 25.0. Armonk, NY: IBM Corp.) We also calculated PSA area under the curve (AUC) and predictive positive value (PPV) to predict PCa.

Results: 41 (77,4%) of the biopsied PI-RADS 3 lesions were benign conditions and 12 (22,6%) proved to be a PCa. On univariate analysis, there were no statistically significant differences in patients who have PIRADS 3 lesion on mpMRI and malignant disease (PCa) or not in age, pre-operative PSA, PV, PSAD, lesion size, presence of multifocality on mpMRI or being biopsy-naïve or not. Histopathological diagnose of PCa in patients with PIRADS 3 lesions were associated with peripheric lesions (p=0,048 OR: 5,25; CI95%: 1,021-26,948). The AUC to predict any PIRADS 3 with PCa was 0,716 (CI 95% 0,576-0,832 P=0,0084) for PSA. The highest Youden’s Index was at PSA <5,7ng/mL with the sensibility of 83,3% and specificity of 75,61% for the diagnosis of PCa. The PPV was 49,93% (CI 95% 35,47-64,4%).

Conclusions: Peripheric PI-RADS 3 lesions should be seen as an indicator of the necessity of targeted biopsy. PSA demonstrated to have a lower PVV to predict PCa in patients with PI-RADS 3 lesions.

João Pina*; Thiago Andrade Guimarães; Hugo Pinheiro; Francisco Fernandes; João Cunha; João Pedro Ferreira Guerra; Luís Campos Pinheiro *Centro Hospitalar Universitário de Lisboa Central, Lisbon, Portugal

Introduction & Objectives: According to recent data from the Global Cancer Observatory, published in March 2021, Portugal experienced 6750 new cases of PCa in 2020, which demonstrates its high incidence in a country with 10 344 802 inhabitants. Here, we aim to evaluate Portuguese data from patients who were subjected to MRI/US-FB due to PI-RADS>=3 lesions in tertiary referral center to the available literature.

Materials & Methods: We retrospectively analyzed a confidential database of patients with PI-RADS abnormality subjected to MRI/ US-FB between October 2020 and April 2022 in our institution. Baseline characteristics of patients and pathological outcomes were compares using Student-t-test (age, PSA, PSAD, prostatic volume (PV) and lesion size, total of cylinders collected and percentage of positive cylinders). Chi-square test was used for categorical data (peripheric lesion; multifocality; biopsy-naïve; presence of PCa; neural invasion; lymph vascular invasion; cribriform pattern; intraductal pattern and EPE. A P- value < 0,05 was considered statistically significant.

Results: We have evaluated 130 patients. The proportions of patients with PI-RADS 3, 4 and 5 lesions were 44,2% (n=53), 40% (n=52) and 19,2% (n=25). According to one-way ANOVA, there were statistically significant differences between PI-RADS 3,4 and 5 groups in age (p=0,030), pre-operative PSA (p=0,014), PSAD (p=0,19) and lesion’s size (p<0,001). Bonferroni post hoc test demonstrated that those difference were higher among patients with PI-RADS 3 lesions when compared to PI-RADS 5 group in age (p=0,025), pre-operative PSA (p=0,042), PSAD (p=0,038) and lesion size (p<0,001). Bonferroni post hoc test also demonstrated differences between PI-RADS 4 group and 5 in pre-operative PSA (p=0,013), PSAD (p=0,024) and lesion size (p<0,001). There were no differences in Bonferroni post hoc test between PI-RADS 3 and 4 groups. Chi-square test showed statistically significant differences between PI-RADS 3,4 and 5 groups regarding peripheric lesions (p<0,001) and the incidence of PCa among groups (<0,001). Patients with PIRADS-5 have more proportions of lesions characterized as peripheric in mpMRI (96%), when compared to PI-RADS 4 (78%) and PI-RADS 3 (56,6%). The proportions of patients with PCa is exceptionally higher in the PI-RADS 5 group (96%; n=24) when compared to PI-RADS 4 (61,5%; n=32) or PI-RADS 3 (22,6%; n=12). There was no difference regarding PV (p=0.108) and number of cylinders collected during MRI/US-FB (p=0,053), presence of multifocality on mpMRI, (p=0,418) or being biopsy-naïve or not (p=0,823).

Conclusions: The incidence of PCa in Portuguese patients classified according to PI-RADS v2.1 are aligned with the current literature. The incidence of PCa in PI-RADS 5 lesions is exceptionally higher in our cohort. Patients with PI-RADS 5 lesions have more concomitant suspicious parameters that indicate higher risk of PCa, including older age, higher PSA and PSAD, higher lesion size, mostly peripheric when comparing to patients with PI-RADS<=4 lesions.

19 Portuguese population real data about the incidence of prostate cancer in patients with PI-RADS 3, 4 and 5 lesions: a retrospective analysis

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Exploring prostate cancer patients’ characteristics to identify parameters that can predict clinically significant prostate cancer

João Pina*; Thiago Andrade Guimarães; Hugo Pinheiro; Mariana Silva Medeiros; Vanessa Andrade; João Cunha; Francisco Fernandes; Luís Campos Pinheiro *Centro Hospitalar Universitário de Lisboa Central, Lisbon, Portugal

Introduction & Objectives: The ability of MRI to detect clinically significant prostate cancer (csPCa) is important to select patients for prostate biopsy. Here, we aim to compare clinical and pathological characteristics of patients with csPCa subjected to MRI-US/FB.

Materials & Methods: We retrospectively analyzed a confidential database of patients with prostate cancer subjected to MRI/US-FB between October 2020 and April 2022. We stratified patient in 2 groups (ISU 1 group or ISUP>=2 group). Baseline characteristics of patients and pathological outcomes were compares using Student-t-test (age, PSA, PSAD, prostatic volume (PV) and index lesion size, total of cylinders collected and percentage of positive cylinders). Chi-square test was used for categorical data (peripheric lesion; multifocality; biopsy-naïve; neural invasion; lymph vascular invasion; cribriform and intraductal pattern). A P-value < 0,05 was considered statistically significant. Those statistical analysis was performed using SPSS v.25 (IBM SPSS Statistics for macOS, Version 25.0. Armonk, NY: IBM Corp.) We also calculated PSAD, PI-RADS and index lesion size area under the curve (AUC) and predictive positive value (PPV) to predict csPCa.

Results: 68 patients with PCa were identified. Overall, 18 (26,5%) patients presented with non-csPCa against 50 (73,5%) who presented with csPCa. On univariate analysis there were no statistically significant differences between both groups of patients regarding age, pre-operative PSA, PSAD, PV, multifocality, presence of cribriform or intraductal pattern. PI-RADS score was very close to achieve statistical significance (p=0,053). In this cohort, as higher was PI-RADS score, higher was the percentage of patients with csPCa. Lesion size (p= 0,029), the percentage of positive cylinders (p=0,003) and neural invasion detected by MRI/US-FB were associated with the presence of csPCa. The AUC to predict any csPCa was 0,673 (CI 95% 0,549-0,782 P=0,0192) for PIRADS. The highest Youden’s Index was at PIRADS >4 with the sensibility of 42% and specificity of 83,3% for the diagnosis of csPCa. The PPV was 87,462% (CI 95% 70,28-95,37%). The AUC to predict any csPCa was 0,672 (CI 95% 0,548-0,781 P=0,023) for index lesion size. The highest Youden’s Index was achieved for lesions with >8mm with the sensibility of 90% and specificity of 38,89% for the diagnosis of csPCa. The PPV was 80,33% (CI 95% 73,64-85,66%). On the other hand, the AUC to predict any csPCA was 0,728 for PSAD (CI 95%: 0,607-0,829 P=0,0038). The highest Youden’s Index was at PSAD>0,1ng/mL2 (sensitivity of 84% and specificity of 61,1%). The PPV was 85,69% (CI 95%: 76,83-91,54%).

Conclusions: Patients with csPCa have higher index lesion size, % of positive cylinders, more prevalence of cribriform pattern and neural invasion than non-csPCa patients. As higher is the PIRADS score, index lesion size and PSAD, higher is the probability of csPCA.

Ken O'Byrne*; Danielle Meyrick; Neel Patel; Colin Hayward *Princess Alexandra Hospital, Queensland University of Technology, Translational Research Institute, Brisbane, Australia

Introduction & Objectives: The cell surface glycoprotein prostate-specific membrane antigen (PSMA) has proven to be an ideal therapeutic target in prostate cancer (PC) as it is highly expressed by malignant prostate cells. 177Lu-DOTA-HuJ591-CHO (TLX591) is a radioimmunoconjugate comprised of the humanized IgG1 mAb rosopatamab, linked to the low energy beta-emitting radioisotope lutetium-177 (177Lu) via the bifunctional chelating agent DOTA-NHS ester. Chinese Hamster Ovary (CHO) cell line has been selected for the manufacture of the recombinant mAb.

There is a strong rationale for investigation of TLX591 as a potential radioligand therapy for the treatment of PC, supported by previous clinical evidence of the safety of the antibody, as unconjugated and as a DOTA conjugate, and of the specificity of the antibody for PC tumors.

This multicenter Phase 1 study (ClinicalTrials.gov Identifier: NCT04786847) is designed to evaluate the safety, tolerability, biodistribution and dosimetry of TLX591 administered with best SoC to patients with PSMA-expressing, metastatic castrationresistant prostate cancer (mCRPC) progressing despite prior treatment with a novel androgen axis drug (NAAD). This study is currently in progress.

Materials & Methods: The study will consist of 2 cohorts:

Cohort 1: Five patients will be recruited for evaluation of biodistribution of TLX591 administered in combination with SoC. These patients will receive a single tracer (27 mCi) intravenous (IV) infusion of TLX591, and SPECT images and pharmacokinetic blood samples acquired at several time points until Day 13.

A qualitative comparison of biodistribution of tracer level TLX591, as demonstrated by SPECT, with 68Ga-PSMA-11 on PET imaging will be performed to ensure equivalent (or improved) radiopharmaceutical tumour targeting. Dosimetry analysis will also be performed. If safety is confirmed by independent DSMB review, each individual patient in Cohort 1 will proceed 14 days following the initial tracer dose to a second administration of TLX591. SoC therapy will continue according to standard practice.

Cohort 2: All further enrolled patients will receive two administrations of 76 mCi TLX591 for further evaluation of safety, tolerability and biodistribution, and efficacy in combination with SoC.

177Lu-DOTA-TLX591 safety, biodistribution and dosimetry study (ProstACT-SELECT)

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Case reports

1 Rare case of primary adenocarcinoma of the seminal vesicles

Zoi Ziakouli*; Christina Armpilia; Lymperopoulou Georgia; Alexioy Despina; Protopapa Maria; Maria Grenzelia; Katsarou Eleni; Koukourakis Ioannis; Dimitra Desse; Kouloulias Vasileios; Zygogianni Anna *National and Kapodistrian University, Athens, Greece

Introduction: Primary adenocarcinoma of the seminal vesicles is a rare tumor, with limited number of case reports in the international literature [1]. Its unusual presentation and lack of large series of patients render difficult the establishment of therapeutic guidelines [2]. We report the long-term follow-up of a patient with primary adenocarcinoma of the seminal vesicles, treated with surgery and postoperative radiotherapy.

Clinical findings: A 59-year-old patient with abdominal pain and bowel evacuation disorder was admitted to hospital. Contrastenhanced imaging showed a 9 cm mass in the rectovesical pouch, stemming from the seminal vesicles. No distant metastatic spread was proved after complete staging. CA 125 was found raised (50 iu/ml). The patient underwent resection of the cystic mass and radical prostatectomy, including the excision of the seminal vesicles, on December 2014. The pathology report confirmed the diagnosis of adenocarcinoma of the seminal vesicles, extending to the surrounding fibroadipose tissue without invading the prostate gland. Surgical margins were positive. The results of immunohistochemistry study indicated wide positivity of neoplastic cells for CD7, regional positivity for CA 125, rare expression of CK20, while PSA and p63 were negative.

Treatment: The patient received adjuvant 3D conformal radiation therapy (45Gy/25 fractions to the pelvis and a boost dose of 20Gy/10 fractions to the tumor bed). Hormone therapy was prescribed for 2 years following the completion of radiation therapy. After treatment completion, the patient was regularly evaluated, every 6 months, with MRI of the pelvis, CT of the abdomen and chest, as well as monitoring of serum CA 125 and PSA. During the last follow-up, performed 7 years after therapy, the patient is alive and free of locoregional relapse or distant metastases.

Conclusions: Primary adenocarcinoma of the seminal vesicles is a rare disease with uncertain prognosis. Our experience suggests that surgery and postoperative radiotherapy could have a definitive role in the treatment of this carcinoma.

References

1. Thiel R, Effert P. Primary adenocarcinoma of the seminal vesicles. J Urol. 2002;168(5):1891-1896. doi:10.1097/01.ju.0000032701.96997.e4

2. Ormsby AH, Haskell R, Jones D, Goldblum JR. Primary seminal vesicle carcinoma: an immunohistochemical analysis of four cases. Mod Pathol. 2000;13(1):46-51. doi:10.1038/modpathol.3880008

2 A case of prostate small cell carcinoma associated with paraneoplasic SIADH

Joana Duarte Albuquerque*; Jorge Alves Correia; Teresa Timóteo; José Luís Passos Coelho *Hospital da Luz, Lisbon, Portugal

Introduction: Small-cell-carcinoma (SCC) accounts for 0.5-1% of prostate cancers. It usually presents with markedly enlarged prostate, lymph node (LN) and bone metastases and low PSA relative to disease-burden. SCC has rapid progression with a median-survival <1-year. 10% are secreting-tumors and present with paraneoplastic-syndrome. We report a patient with prostate SCC with a paraneoplasic SIADH of difficult management.

Clinical findings: A 63 yo man presented with a 2 month history of painful left lower limb edema. Doppler-ultrassound excluded deep vein thrombosis and abdomen-pelvic CT and MRI documented a bulky prostatic lesion (61x83x46mm) involving left seminal vesicle, bladder trigone, anterior rectum and obturator muscles; enlarged retrocrural, lateroaortic, bilateral obturator and iliac LN , extending from the emergence of the superiormesenteric-artery to the deep inguinal-region. Bone-scan excluded bone-metastasis. PSA was 1,2ng/dL.

Diagnosis & Treatment: Prostatic biopsy documented a SCC (AE1/AE3+, CAM5.2+, chromogranin+, synaptophysin+, CD56+, CD20-, CD3-, CD38-, CD138-, PSA-, CK7-, CK20-, CDX2+) with a Ki67=90%. Tumor was staged as cT4N1M1a (IVB) and treated with Cisplatin/Etoposide for 6-cycles. After first-treatment, he was hospitalized with symptomatic hyponatremia (nadir 111mmol/L) attributed to Cisplatin (switched to Carboplatin in second-cycle). The pain and lower extremity improved and CT after 5-cycles of chemotherapy documented a partial response (LN and prostate). For better local control, external beam radiation to prostate and obturator LN (55Gy/20Fr and 46Gy/20Fr) was given. Two-months later, he was hospitalized with painful left lower limb edema with inflammatory signs and functional impotence. Disease progression was documented on CT with new retroperitoneal and axillary LN , as well as LN involvement of the iliac-vein and focally occlusive thrombosis of the distal external-iliac-vein (Figure 1 and 2). Anticoagulation and antibiotics were started and stent was placed in external-iliac-vein, with symptomatic improvement. Second-line chemotherapy was started with Carboplatin/ Docetaxel (with Pembrolizumab added on second-cycle); Foundation1® tumor testing did not identify target mutations; PD-L1=0%. Euvolemic hyponatremia (nadir 113mmol/L) due to paraneoplasic SIADH (elevated urinary osmolarity and sodium, with normal ACTH and cortisol) was diagnosed, with partialresponse to water restriction, salt-tablets and loop-diuretics. Until now, patient received 4-cycles of chemotherapy with clinical improvement, despite multiple delays due to persistent hyponatremia (not present in last evalution, with can evidences some disease control) (Figure 3).

Conclusions: The case reported is a rare presentation of SCC prostate cancer, diagnosed as metastatic and bulky disease, which is unresponsive to hormonal manipulation. Management of concomitant paraneoplastic syndromes are challenging and dependent on disease control. First-line treatment consists of platinum/etoposide, typically with prompt response and early recurrence. Promising benefit of immunotherapy in prostate-SCC was reported is phase-Ib trial of pembrolizumab + standard-ofcare chemotherapy with a response-rate of 43% and 12-month PFS of 36%.

Sustained response of apalutamide in non metastatic CPRC

Raquel Clemente Graffigna*; Sara González Nieto; Lara Torres León; Almudena Monllor Méndez; Angelo Jesús Sotillo *Hospital Universitario Nuestra Señora de Candelaria, Tenerife, Spain

Introduction: Although androgen deprivation therapy (ADT) is an effective therapeutic weapon for relapsing prostate cancer after radical treatment most patients develop resistance and disease progression.

The biochemical relapse and absence of metastatic disease indicate the existence of non-metastatic castration-resistant prostate cancer (nmCRPC).

In recent years have been developed androgen receptor inhibitors for nmCRPC treatment that have been shown increase metastasisfree survival. We present our experience with apalutamide for the treatment of two cases of nmCRPC.

Clinical findings: 80-year-old male with a history of prostate adenocarcinoma Gleason 3+3, treated by pelvic radiotherapy with curative intent in 2003. Despite this, the first biochemical progression occurred 5 years later, so intermittent ADD was started.

TDA is restarted indefinitely due to disease progression. In 2018 PSA increased to 21.5 ng/ml with total testosterone levels of 0.25 ng/ml.

Diagnosis & Treatment: Due to biochemical progressiondespite of TDA, we carry out images studies, that were negative for distant disease.

nmCRPC diagnosis was established and treatment with Apalutamide was approved which begins in junio del 2018, maintaining the ADT therapy. The first PSA determination showed a significant decrease, reaching PSA figures of 0.11ng/ml.

The patient has maintained treatment with apalutamide for 49 months, with current PSA figures of 0.02 ng/ml.

During the months of treatment, he has not presented any adverse reaction associated with apalutamide.

Conclusions: Prostate cancer is the most common tumor in european men. It is estimated that CRPCnm accounts for approximately 7% of all prostate tumors.

Apalutamide has been shown significantly increase metastasisfree survival and reduce the rate of PSA in patients with mCRPC at high risk of developing metastatic disease.

It is safe and generally well tolerated, although the most common adverse effects that have been studied include increased risk of seizures, hypertension, cardiovascular events, skin disorders and increased risk of falls.

There are still no studies that compare the efficacy of apalutamide with the other two drugs marketed for the same purpose, enzalutamide and darolutamide.

Figure 1. Lumbar LN after progression Figure 2. LN involvement of the iliac-vein and focally occlusive thrombosis of the distal externaliliac-vein Figure 3. Serum sodium levels over time

23 3

Squamous cell carcinoma of seminal vesicles: a case report and systematic review

Raquel Clemente Graffigna*; Sara González Nieto; Lara Torres León; Almudena Monllor Méndez; Angelo Jesús Sotillo *Hospital Universitario Nuestra Señora de Candelaria, Tenerife, Spain

Introduction: Diagnosis of seminal vesicle carcinoma is a challenge due to its rarity and nonspecific presentation. There are less than 100 cases published in the literature. The most frequent histological type is adenocarcinoma. Only seven cases of squamous cell carcinoma of seminal vesicles have been published (Table 1).

The mean age at diagnosis is 49.4 years. Our patient presents the youngest age of presentation, along with another case of 26 years.

The most common form of presentation is gross hematuria, followed by dificulty urination and dysuria.

Digital rectal examination is a good initial diagnostic method, although non-specific. The PSA was normal in all published cases.

Computed tomography and magnetic resonance imaging confirm the existence of a pelvic mass and provide useful information for surgical management. The definitive diagnostic test is transrectal biopsy of the lesion. We present a case of squamous cell carcinoma of the seminal vesicles and perform a systematic review of published articles.

Clinical findings: A 33-year-old man evaluated for macroscopic hematuria, acute urinary retention and irritative urinary symptoms. Rectal examination revealed a stony mass in the right seminal vesicle. PSA was in normal ranges and testicular tumor markers were negative.

Magnetic resonance imaging showed a VSD-dependent mass. It conditioned a uretero-hydronephrosis and laterally displaced the prostate and bladder.

Diagnosis & Treatment: Transrectal biopsy was compatible with a well-differentiated squamous cell carcinoma of the right seminal vesicle.

The urological tumor committee was decided to start treatment with neoadjuvant chemo-radiotherapy. Subsequently, we was performed radical cystoprostatectomy. Histology showed a poorly differentiated squamous cell carcinoma with involvement of both seminal vesicles, the prostatic stroma and the bladder wall

Conclusions: Squamous seminal vesicle carcinoma is extremely rare. There isn't currently treatment of choice; however, in published cases, surgical excision is recommended as the firstline treatment.

Because the squamous lineage responds favorably to chemoradiotherapy, in several patients it was applied as adjuvant therapy to surgery.

Squamous seminal vesicle carcinoma is a rare pathology, with few cases published in the literature and scarce evidence on its management. It is an aggressive and rapidly progressive disease. Early diagnosis and the intervention of a multidisciplinary team are essential for its prognosis.

24 4

Use of pembrolizumab in castrationresistant prostate cancer with mismatch repair-deficient: first case in our region

Lara Torres León*; Marta Jiménez Navarro; Sara González Nieto; Raquel Clemente Graffigna; Almudena Monllor Méndez *Hospital Universitario Nuestra Señora de la Candelaria, Tenerife, Spain

Introduction: Clinical trials have been published in last years about immune checkpoint inhibitor agents, such as pembrolizumab to be recently approved by the US Food and Drug Administration (FDA) for the treatment of metastatic or unresectable solid tumors that are mismatch repair deficient or microsatellite instability (MSI-H).

Clinical findings: We present a case of 59-year-old male with a personal history of arterial hypertension, ischaemic heart disease, haemorrhagic stroke and colon adenocarcinoma in 2012.

Diagnosis & Treatment: After an episode of urinary retention and detecting an elevated PSA (12.82 ng/ml in March 2019), a transrectal prostate biopsy diagnosed bilateral Gleason 5 + 5 prostate adenocarcinoma with perineural infiltration. A CT and MRI extension study revealed a locoregionally advanced prostatic neoformation with left iliac adenopathy, infiltration of the rectum and bladder floor, associated with a probable tumor implantation in the left mesorectum (T4N1Mx). Bone scintigraphy ruled out bone metastases and PET-choline confirmed bilateral iliac adenopathies and radiotracer avidity of the nodular lesion in the left mesorectum (image 1). Given the advanced stage, uro-oncology committee decided to start chemotherapy with Docetaxel x 6 cycles (June-October 2019) + androgen deprivation therapy. PET-Choline (January 2020) revealed partial response with persistent consumption of the prostate, so he started radical pelvic radiotherapy on the primary tumor and iliac chains (March-April 2020). A new CT scan (April 2021) showed local periprostatic progression and rectal involvement. He became castration resistance, so he started 1st line treatment with Enzalutamide (May-September 2021). Colonoscopy was requested that diagnosed synchronous cecal carcinoma (right hemicolectomy in July 2021 pT2N0M0). Local progression was observed on September CT scan with an increase in the size of the lesions and elevated PSA. He started 2nd line treatment with 5 cycles of Cabazitaxel (September-December 2021) and new external irradiation treatment with palliative intent on pelvic implants. New CT scan (January 2022) showed extension to the penis base and anus with infiltration of the external sphincter. The patient suffered an episode of lower intestinal occlusion secondary to tumor infiltration, requiring a terminal colostomy. Given the poor response to the treatments offered, a molecular study (somatic and germinal) of the first prostate biopsy specimen was requested, demonstrating mismatch repair-deficient (MMR) and microsatellite instability (MSI). Pembrolizumab was started, according to the KEYNOTE-158 study, in March 2022. Nowadays he´s on 7th maintenance cycle, without local progression at imaging tests, and the current PSA is undetectable (0.02 ng/ml). Furthermore, patient reports improvement in pain secondary to perineal involvement.

Conclusions: Immunotherapy for CRPC is now much more widely available. Since the publication of the phase II study MDX010 (Ipilimumab in CRPC) in 2013, new treatment alternatives have been introduced that modify the course of the disease and improve patients' quality of life.

Image 1. PET-choline image with prostate involvement and extraglandular extension (a) PET-choline image with radiotracer-avid nodule in left mesorectum (b)

25 5

Case report and review of literature of a rare case of prostatic carcinosarcoma

Vanessa Andrade* *Centro Hospitalar Universitário de Lisboa Central, Lisbon, Portugal

Introduction: Prostatic carcinosarcomas are extremely rare, representing less than 0,1% of all prostate cancers. We report a case from a patient of our centre diagnosed with carcinosarcoma after a Millin prostatectomy. A review of the literature was also peformed.

Clinical findings: We report a case of a 68 years old patient diagnosed due to a surgery to benign prostatic hyperplasia. He had some infectious complications after that, needing admission to the hospital and specific management.

Treatment: He was treated with chemotherapy and hormonal treatment, initially with some response, but later with progression of disease and worsening of his general status, which became fatal after 13 months after diagnosis.

Conclusions: Carcinosarcoma is a rare and extremely aggressive entity. Unfortunately, it has a really bad prognosis and, as we seen, became fatal to our patient. Due to the reduced number of cases, it still lacking recommendations regarding the best treatment options. In the majority of patients, surgery, chemotherapy and radiotherapy are valid options.

Sara González Nieto*; Lara Torres León; Raquel Clemente Graffigna; Almudena Monllor Méndez; Marta Jiménez Navarro *Hospital Universitario Nuestra Señora de Candelaria, Tenerife, Spain

Introduction: According to literature, patients with Low Risk Prostate Cancer (PSA < 10 ng/mL and GS < 7 (ISUP grade 1) and cT1-2a) suggests that the intermediate and long-term risks of metastasis are low in men who have Gleason score 6 (GS6) disease at diagnosis.

Clinical findings: We present a 53 year-old male patient with history of prostate cancer, who underwent a robotic-assisted radical prostatectomy in july 2019. Pathology demonstrated a prostate cancer Gleason 3+3 (as seen in prostate biopsy prior to surgery) pT2NxR0, with 1.08 postoperative PSA. Bone scan, CT scan and Pelvic MRI were performed, showing no metastasis, so after discussing the case in a Multidisciplinary Team (MDT), the decision was to keep monitoring the patient with PSA. It went up to 2.7, so Bone scan, CT scan and Pelvic MRI were performed again, without finding any lesion; MTD decided to ask for a 18F-choline PET, which didn’t demonstrate any metastasis. PSA kept ascending up to 3.54. On DRE there was an undetermined area that was biopsied; pathology showed normal prostatic tissue with no malignancies. A PSMA PET/CT was performed (previously not available in our area), demonstrating 2 rib metastasis.

Treatment: After discussing the case with MTD, it was decided to treat the patient with Androgen Receptor Targeted Treatment (ARTA) + Radiotherapy on the 2 rib metastasis.

Conclusions: According to data published so far, PSMA PET/ CT detcs residual tumor 15-58% when PSA is 0.2-0.5ng/ml, 2573% when PSA is 0.5-1 ng/ml, 69-100% when PSA is >2 ng/ml. Although our patient had a low risk prostate cancer, we believe that we could have diagnosed the bone metastasis sooner with PSMA PET/CT. Thanks to these new diagnosic techniques we will be able to improve suvellaice in this type of patients.

7 Persistant PSA after radical prostatectomy secondary to bone metastasis in low risk prostate cancer: a case report

26 6

Priapism. First symptom in prostate cancer

José Luis Rodríguez*; Javier Aranda Pérez; Fernando Pareja Peña; María Murgui Rodríguez; Luis Alberto García Martín; Jesús Ángel Olivares Ruíz del Olmo; Gabriel Alejandro Machado Fernández; Inmaculada Bravo Fernández *Hospital Universitario, Cáceres, Spain

Introduction: Priapism is an urological emergency. It consists of an abnormally prolonged erection (>4 hours). It can be differentiated etiologically between primary or secondary priapism. Among the main etiologies, we can discuss about hematological diseases or iatrogenesis. An uncommon cause of priapism is involvement by oncological processes. (3-8%) We will focus about priapism in locally advanced prostate cancer.

Clinical findings: A 78-year-old patient with a personal history of connatal idiopathic. Previous surgical intervention for right inguinal herniorrhaphy. Permanent bladder catheterization due to acute urinary retention episode. Performance status 0. In November 2020 he was admitted to internal medicine service in context of deterioration of general condition with symptoms of weakness and dizziness. Internal medicine department consulted urology department for penile pain.

Diagnosis & Treatment: Physical examination revealed induration of proximal penis extending to the median raphe and perineum. That suggested us an oncologic process. Erection was constant. Nodular lesions were observed on the glans penis (x3). The patient was diagnosed by priapism.

First we performed drainage of corpora cavernosa + phenylephrine infiltration without achieving penile detumescence. Then we decided to perform surgical techniques for the treatment of priapism. We performed distal penile bypass techniques. We opted for Winter and Al Ghorab Techniques. After this, penile induration persisted. Abdomino-pelvic CT scan revealed an enlarged prostate with irregular borders extending towards the base of the penis and contacting the rectum. PSA was requested with a value of 97 ng/mL.

Urethrocystoscopy showed nodular lesions in the entire urethra with impossibility of bladder access. Biopsies of the urethral lesion, cavernosum corpus and nodular lesion in glans penis were sent to pathological anatomy. Anatomopathological result was adenocarcinoma compatible with prostatic origin. We requested systematic prostate biopsy to confirm diagnosis. Anatomopathological result was prostate adenocarcinoma Gleason 8 (4+4) in all samples. Extension study in April 2020 was positive for bone metastases in pelvis and left femur.

Outcomes & follow-up: After all the patient received androgen deprivation therapy. At this moment, palliative care department is responsible of patient’s symptoms management.

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