Global Congress on Prostate Cancer 2021: Abstract book

9th edition

Abstract book LIVE & VIRTUAL MEETING 12 & 13 October 2021

All abstracts are available online • Browse published posters • Contact authors directly You can find an overview of all accepted abstracts on https://www.morressier.com/event/ prosca2021/61373e55fb6e8400130d57e0.

ORGANISING COMMITTEE OF THE CONGRESS Amit Bahl, Bristol Haematology & Oncology Centre, Bristol, UK Piet Dirix, Radiation, Iridium Cancer Network, Antwerp, Belgium Piet Ost, GZA Sint Augustinus, Antwerp & Ghent University, Ghent, Belgium Brieuc Sautois, CHU de Liège, Liège, Belgium Ash Tewari, Icahn School of Medicine at Mount Sinai, New York, USA Bertrand Tombal, University Hospital Saint-Luc, Brussels, Belgium Siska Van Bruwaene, AZ Groeninge, Kortrijk & University Hospital, Leuven, Belgium

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ABSTRACTS OF THE GLOBAL CONGRESS ON PROSTATE CANCER, 9TH EDITION LIVE & VIRTUAL MEETING, 12 & 13 OCTOBER 2021

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Materials & Methods: A prospective, multicenter and interventional phase I/II pilot study using Soractelite™ with an ablate-and-resect principle was designed that aims to include 15 patients. Patients underwent TPLA procedures, using a single fiber delivering 1800J at 3W or 5W under local anesthesia, with continuous ultrasound guidance approximately 4 weeks before RP. Imaging (grayscale US, CEUS and mpMRI) was performed prior to TPLA and RP. Whole-mount H&E-stained slides of RP specimens were digitized. The ablation zone was annotated on imaging and histology, and segmented into 3D models.

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Preliminary results of in vivo focal transperineal laser ablation treatment of the prostate: correlation of mpMRI and CEUS imaging to histology in radical prostatectomy specimen

Results: Eleven outpatient clinic based TPLA procedures were performed successfully and discharged the same day. The ablation zone on T2-weighted, DCE and CEUS imaging was clearly demarcated upon qualitative analysis and the 3D shape seems to be ellipsoid on MRI and CEUS. This closely matches the annotated ablation zone histology. Currently, quantitative data, regarding 3D segmentation of T2-weighted, DCE, CEUS and histopathology, is being analyzed to be presented.

Luigi A.M.J.G. van Riel, Academic Medical Center Rob A.A. van Kollenburg, Theo M. de Reijke, C. Dilara Savci - Heijink, Marc R.W. Engelbrecht, Harrie P. Beerlage, Ton G. van Leeuwen, D. Martijn de Bruin, Jorg R. Oddens Introduction & Objectives: Focal ablative techniques are an alternative for standard radical therapy of localized prostate cancer (PCa). Soractelite™ transperineal laser ablation (TPLA) using the Echolaser device, with four independent laser sources, is such a novel minimal invasive treatment. We conducted a study in patients planned for radical prostatectomy (RP) to determine the histological ablative efficacy. The 3D size of ablation zone on RP specimens was correlated to CEUS imaging and MRI following TPLA. Furthermore, safety and feasibility of TPLA using a (multi) fiber setup in men with localized PCa will be evaluated.

Conclusion: TPLA is a feasible office-based minimal invasive focal treatment of PCa and it can be performed safely under local anesthesia, in these preliminary results. Multiple laser fiber configurations will be investigated with ongoing enrollment. The ablation zone is clearly demarcated on CEUS imaging and on MRI T2-weighted and DCE imaging. The histopathological defined 3D ablation zone closely matches the ablation zone seen on imaging.

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68Ga PSMA PET/CT for staging high risk prostate cancer patients suitable for radical treatments: effective clinic implication and preliminary diagnostic performance

ADC map parameters at mpMRI predict unfavorable cribriform pattern in PCa patients Lorenzo Bianchi, IRCCS Azienda Ospedaliero-Universitaria Policlinico di S. Orsola Pietro Piazza, Caterina Gaudiano, Antonio De Cinque, Lorenzo Bianchi, Arianna Rustici, Matteo Droghetti, Beniamino Corcioni, Francesco Chessa, Amelio Ercolino, Federica Farneti, Riccardo Schiavina, Rita Golfieri, Eugenio Brunocilla

Lorenzo Bianchi, IRCCS Azienda Ospedaliero-Universitaria Policlinico di S. Orsola Francesco Mattana, Eleonora Balestrazzi, Riccardo Mei, Andrea Farolfi, Andrea Angiolini, Matteo Droghetti, Amelio Ercolino, Federica Farneti, Francesco Medici, Alessio Giuseppe Morganti, Alberto Briganti, Francesco Montorsi, Riccardo Schiavina, Eugenio Brunocilla, Paolo Castellucci, Stefano Fanti

Introduction & Objectives: Several studies have showed that cribriform (CR) prostate cancer (PCa) is associated with adverse clinical outcomes. Early detection of these tumors could lead to tailored therapies or follow-up protocols. The aim of the study was to assess the role of multiparametric MRI (mpMRI) parameters in early identification of CR PCa.

Introduction & Objectives: Prostate Specific Membrane Antigen-PET/CT (PSMA-PET/CT) for staging high-risk prostate cancer (PCa) patients might overcome limits of conventional imaging. Accurate staging of patients suitable for radical treatments may significantly change the treatment management.

We aimed to assess the management changes after PSMA-PET/CT in high risk patients before the scheduled radical prostatectomy + extended pelvic lymph node dissection [RP+ePLND] or radiotherapy [RT]). In a subgroup of patients who subsequently underwent RP, we aimed to evaluate the diagnostic performance of PSMA to detect lymph node metastases (LNM), using histology as reference standard.

Materials & Methods: We retrospectively evaluated 163 patients who underwent RARP for clinically significant PCa (csPCa) at single tertiary center. All patients underwent preoperative mpMRI and lesions were scored according to PIRADSv2.1. Pathologic specimens were evaluated by single experienced pathologist.

Patients with negative mpMRI (namely, PIRADSv2.1 ≤2, n=28) were excluded. Overall, 135 patients with positive mpMRI (namely, PIRADSv2.1 >2) were stratified according to presence of consistent CR pattern (>50%) and absent or minimal CR pattern (≤50%) at RARP specimen. Difference between the two groups were evaluated with Mann-Whitney U test and chi-square test to compare medians and proportions, respectively. Multivariate logistic regression was used to identify predictors of CR>50% among mpMRI phases and parameters, in patients with positive mpMRI in the peripheral zone (n=111). ROC curve was used to evaluate the area under the curve (AUC) of Apparent Diffusion Coefficient (ADC) in detecting lesions harboring CR>50%.

Materials & Methods: Patients were enrolled according to the following criteria1) histopathologic diagnosis of PCa, treatment naïve, high-risk according to D’Amico, suitable for radical treatment RP or RT; 2) 68Ga-PSMA-PET/CT performed for staging proposal.

We analyzed the impact of PSMA PET/CT on the intention to treat (ITT) based on a MDT decision before and after PSMA-PET/CT. The diagnostic performance of PSMA PET/CT in the detection of LNM was evaluated in a subgroup of 27 patients who underwent RP+ ePLND, using histology as reference standard. ROC curve analysis was employed to calculate the Area Under the Curve (AUC) of PSMA-PET/CT to predict LNM.

Results: Median age was 66 years and median PSA was 6.5 ng/ml.

Overall, ISUP grade at final pathology was 2,3,4 and 5 in 78 (48%), 53 (32%), 19 (12%) and 13 (8%) patients, respectively. Considering 135 men with positive mpMRI, 30 (22.2%) and 105 (77.8%) men harbored CR>50% and CR≤50% at final pathology. Patients with CR>50% had significantly higher index lesion’s diameter (14 vs.

13mm, p=0.03) and lower ADC value of both the whole area (0.82 vs 0.94 x10-3mm2/sec, p=0.02) and ADC of darkest zone (0.6 vs 0.75 x10-3 mm2/sec, p=0.03) when compared with patients with CR≤50%. All CR>50% lesions were located in peripheral zone (100 vs 80%, p=0.03) as referred to lesion with CR≤50. At multivariable logistic regression, ADC value of all area (OR 0.025, p=0.03) and ISUP grade 4-5 (OR 6.3, p=0.004) in patients with peripheral mpMRI lesions were independent predictors of CR>50% at definitive pathology. AUC of the ADC of all area was 0.69 (CI 0.560.8, p=0.003).

Results: Overall, 88 patients were enrolled (mean age was 66 yo and mean PSA level was 13.1 ng/ml). Before PSMA PET/CT the scheduled treatment were: 66 RP + ePLND and 22 RT, respectively.

Overall PSMA PET/CT was positive for metastatic disease in 51 patients (58%): LNM in 12 patients (14%), skeletal lesions in 24 (27%), LNM + skeletal lesion 12 (14%) and visceral metastases in 3 (3%). After PSMA PET/CT, the following treatments were performed: 48 (55%) RP+ePLND; 7 (8%) RP+PLND+stereotactic RT (SBRT); 13 (15%) whole pelvis RT+ Androgen Deprivation Therapy (ADT); 8 (9%) whole pelvis RT + SBRT, 2 (2%) ADT, 10 (11%) Docetaxel+ADT. Overall, 12 (14%) patients had major treatment’s change; from planned RP+ePLND or whole pelvis RT to ADT or Docetaxel + ADT); while 15 (17%) had minor treatment’s change: RP+ePLND + SBRT or whole pelvis RT + SBRT. In the subgroups of 27 who underwent RP+ePLND, 8 (30%) had LNM on histology. On a patient-based analysis, PSMA PET/CT showed 57% sensitivity, 95% specificity, 86% NPV and 80% PPV and with AUC of 0.72 in the detection of LNM.

Conclusion: ADC map at mpMRI can be useful to predict the presence of unfavorable CR pattern PCa.

Conclusion: PSMA PET/CT had a major impact on management in 14% and a minor impact on 17% of the population. These results confirm the published literature in the same setting of patients and might encourage the extensive use of PSMA in this setting of patients. PSMA PET/CT showed good accuracy (especially specificity) in the detection of LNM.

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Augmented reality to guide intraoperative frozen section during robot-assisted radical prostatectomy

External validation of a nomogram for predicting 68Ga-PSMA PET/ CT detection rate in patients with prostate cancer recurrence: a clinical tool to guide physicians before suggesting 68Ga-PSMA PET/CT

Lorenzo Bianchi, IRCCS Azienda Ospedaliero-Universitaria Policlinico di S. Orsola Riccardo Schiavina, Francesco Chessa, Andrea Angiolini, Laura Cercenelli, Simone Lodi, Barbara Bortolani, Enrico Molinaroli, Carlo Casablanca, Amelio Ercolino, Federica Farneti, Caterina Gaudiano, Angelo Mottaran, Angelo Porreca, Rita Golfieri, Daniele Romagnoli, Francesca Giunchi

Lorenzo Bianchi, IRCCS Azienda Ospedaliero-Universitaria Policlinico di S. Orsola Francesco Ceci, Matteo Droghetti, Paolo Castellucci, Carlos Artigas, Andrea Farolfi, Amelio Ercolino, Federica Farneti, Riccardo Schiavina, Eugenio Brunocilla, Stefano Fanti

Introduction & Objectives: To propose a novel technique of Intraoperative Frozen Section (IFS) analysis targeted to the index lesion by using augmented reality-3D models (AR-3D) in patients with prostate cancer (PCa) scheduled for nerve-sparing (NS) robot-assisted radical prostatectomy (RARP) and to evaluate its impact on positive surgical margin (PSM) and neurovascular bundles (NVBs) preservation.

Introduction & Objectives: Prostate Specific Membrane Antigen (PSMA) functional imaging has proved to have a significant clinical impact in re-staging prostate cancer (PCa) patients. However, a non-negligible proportion of exams had false negative results. Recently, we proposed a nomogram to identify patients with positive PSMA PET/C in different clinical settings.

We aimed to assess the predictive accuracy (PA), the best cut-off value and the clinical impact of our recent published nomogram through an external validation of multicentric cohort.

Materials & Methods: We prospectively enrolled patients with diagnosis of PCa basing on positive multiparametric Magnetic Resonance Imaging (mpMRI)-targeted Fusion biopsy at the index lesion and preoperative preserved erectile function scheduled for NS RARP. Overall, 20 consecutive patients underwent NSRARP with IFS directed to the index lesion with the help of AR3D (study group). D2PTM software was adopted to segment the healthy prostatic gland, the index lesion, the urinary sphincter and the NVBs from mpMRI images. A 3D view of the virtual model obtained using Meshmixer software was superimposed on the surgical field with vMIX, through DaVinci TilePro connection and real-time manual alignment has been carried out by a biomedical engineer using a 6 degrees of freedom 3D mouse. The surgeon performed RARP with the 3D model overlapped by AR inside the robotic console with implementation of real-time IFS analysis directed to the index lesion projected by the AR-3D guidance. In case of first postero-lateral positive IFS the surgeon proceeded with neuro-vascular bundle resection; in case of fist apical or basal positive IFS the AR-3D model was used again to guide the resection of further sample of periprostatic tissue nearby the index lesion projected by AR-3D. Control group consists of 20 patients underwent standard mpMRI-guided NS RARP without the aid of the AR-3D technology neither IFS analysis and matched with study group by 1:1 propensity-score adjusted for age, clinical stage based on mpMRI, PIRADS score-v2, clinical ISUP grade and PSA. Chi-squared test was used to compare proportion between the two groups.

Materials & Methods: We retrospectively enrolled 1639 PCa patients from 6 institutions with confirmed biochemical recurrence (BCR) after radical treatment for PCa that underwent 68Ga-PSMA PET/CT to identify recurrence. First, the detection rate of 68Ga-PSMA PET/CT was evaluated. Second, a multivariable logistic regression model was used to evaluate predictors for 68Ga-PSMA PET/CT positivity. External validation was performed using the same regression coefficients of previous nomogram: ISUP group, PSA at PET/CT scan, PSA doubling time (PSAdt), ongoing androgen deprivation therapy [ADT], time to BCR (≤12 months vs >12 months) and clinical setting (First BCR [group 1], BCR after salvage therapy [group 2], PSA persistence [group 3] and advanced- stage PCa before second-line systemic therapies [group 4]). The performance characteristics of the model were assessed by quantifying PA, according to model calibration, in order to graphically investigate the extent of overestimation or underestimation. Finally, decision-curve analysis was performed to evaluate the net-benefit of the proposed nomogram.

Results: Median PSA at PSMA PET/CT was 0.78 ng/ml (IQR 0.4- 1.72). In the external cohort, the overall detection rate of PSMA-PET/CT was 53.8% vs. 51.2% in the original population.

68Ga-PSMA PET/CT overall detection rate was 43.5 %, 57.3 %, 59% and 85.9 % in group 1,2,3 and 4, respectively (p<0.001). At multivariable analysis ISUP grade group (ISUP 5 OR 1.76), PSA at PET/CT (0.5 – 0.99ng/mL OR 3.64; 1 – 1.99 ng/mL OR 6.27; >2ng/ mL OR 13.48), PSAdt (6-11.9 months OR 2.84; 3-5.9 months OR 9.12; <3 months OR 14.21) and the clinical setting (group 2, OR 1.37 and group 4, OR 5.13) were found to be independent predictors of positive 68Ga-PSMA PET/CT results (all p≤0.02). The PA of the nomogram in the external validation was identical to that reported in the original model (82% vs. 82%, respectively).

The resulting nomogram showed optimal calibration curve (mean absolute error 0.019). The decision-curve analysis depicted a clinical net-benefit for risk thresholds higher than 20%.

Results: No significant differences between the two groups concerning the covariate used for the propensity score match were found. Patients who underwent AR-3D guided RARP with IFS received higher proportion of unilateral and bilateral NS compared to control group (25% vs. 20% and 65% vs. 45%, p=0.009, respectively) and higher proportion of Grade 1 NS compared to control group (42.5% vs. 20%, p=0.002). Overall, PSM rates were comparable for AR-3D guided IFS RARP and mpMRI guided RARP (15% vs 25%, p=0.2). However, PSM at level of the index lesion were significantly lower in study group (5%) compared to control group (20%, p=0.02).

Conclusion: The proposed technique of IFS analysis targeted to the index lesion guided by AR-3D technology can be useful to improve the precision of surgical dissection during RARP, to reduce PSM at level of the index lesion and to increase the preservation of NVBs.

Conclusions: Our proposed nomogram showed good predictive performance in external validation population and could help clinicians to choose which patients could benefit most from 68Ga-PSMA PET/CT.

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Head-to-head comparison of prostate cancer detection rate at MRI-targeted FUSION biopsy between hub and spoke mpMRI Italian centers

Negative mpMRI targeted prostate biopsy: natural history and clinical management at short-term follow-up Lorenzo Bianchi, IRCCS Azienda Ospedaliero-Universitaria Policlinico di S. Orsola Matteo Droghetti, Lorenzo Bianchi, Eleonora Balestrazzi, Giulia Milani, Carlo Roveroni, Alberto Feruzzi, Carlo Beretta, Amelio Ercolino, Pietro Piazza, Federica Farneti, Caterina Gaudiano, Beniamino Corcioni, Rita Golfieri, Riccardo Schiavina, Eugenio Brunocilla

Lorenzo Bianchi, IRCCS Azienda Ospedaliero-Universitaria Policlinico di S. Orsola Matteo Droghetti, Lorenzo Bianchi, Giuseppe Lando, Carlo Roveroni, Marco Salvador, Carlo Beretta, Eleonora Balestrazzi, Alberto Feruzzi, Giulia Milani, Amelio Ercolino, Federica Farneti, Francesco Chessa, Arianna Rustici, Antonio De Cinque, Caterina Gaudiano, Beniamino Corcioni, Rita Golfieri

Introduction & Objectives: Negative results at multiparametric MRI (mpMRI) targeted Fusion prostate biopsy (TB) could be due to false positive mpMRI findings or due to missed index lesion during TB. We aim to evaluate the follow up and/or further therapeutic approach in men with negative findings at TB with or without a concomitant standard systematic 12-cores biopsy (SB).

Introduction & Objectives: European guidelines on prostate cancer strongly recommend multiparametric MRI before prostate biopsy in patients with clinical suspicion of prostate cancer (PCa).

This led to a progressive widespread of mpMRI even in small nonacademic canters. This could have an impact on mpMRI-targeted biopsy (TB) detection rate, given by possible “false positive targets”. Therefore, we aimed to evaluate the PCa detection rate on TB according to the mpMRI canter’s volume and experience.

Material & Methods: We retrospectively analyzed data from patients who underwent TB with or without concomitant SB for clinical suspicion of prostate cancer (PCa) at our outpatient clinic and suspected Pca at mpMRI (namely PIRADS v.2 score >2). Patients with either TB or SB positive for PCa were excluded from the analyses. Our population was stratified in two groups according to biopsy approach: TB and SB negative for PCa (Group 1) and TB only negative for PCa (Group 2). All biopsies were taken with a transrectal approach. Fusion TB consisted of 3 cores perlesion at mpMRI, using Toshiba Aplio 500 mpMRI Fusion platform.

Procedures were performed by 4 experienced urologists. During follow up, we reported the last PSA value, the necessity of further mpMRI and the histological findings at re-biopsy in case of persistent suspicion of PCa.

Material & Methods: We retrospectively analyzed data of 737 patients who underwent mpMRI TB at our outpatient clinic for suspicion of PCa, using Toshiba Aplio 500™ mpMRI-TRUS Fusion platform. TB was performed with a transrectal approach, taking 3 biopsy cores targeted to the index lesion. TB were performed by 4 expert urologists. All specimens were processed by dedicated pathologists. Patients were stratified according to the center that performed mpMRI: high volume academic (Hub; >300 mpMRI per year) vs. low volume non-academic (Spoke; <300 mpMRI per year) centers. In each center, all lesions were scored using the PI-RADS-v2. Demographics, clinic, radiologic and pathologic information were available for each patient. Differences in detection rate for any PCa and for clinically significant PCa (csPCa) between the two groups were explored. Multivariable logistic regression was used to evaluate predictors of csPCa on TB. The adjustment for casemix included: age, PSA, mpMRI center (Hub vs. Spoke), lesion’s location, PSA density, PI-RADS-v2 score and index lesion’s size.

Results: Overall, 260 patients were included in our analyses: 182 (70%) patients underwent TB and SB while 78 (30%) underwent TB only. Two groups were comparable in terms of age, PSA level, PSA density, prostate volume, mpMRI center’s volume, PIRADS v.2 score, number, location and size of the index lesion. Patients in Group 1 were more likely to be biopsy naïve than those in Group 2 (67.1% vs 28.2%, p=0.001). At median follow-up of 16 months, the median PSA at last follow up and PSA variation compared to pre-biopsy value were 5.6 ng/ml and +0.3ng/ml. Overall, 27 (14.8%) and 17 (21.8%) men repeated further mpMRI in group 1 and group 2, respectively (p=0.2). In Group 2, 18 (23.4%) patients underwent further prostate biopsy while only 9 (4.9%) patients in Group 1 were submitted to re-biopsy (p<0.001). However, 3 (1.6%) and 6 (7.7%) men were diagnosed with PCa in group 1 and group 2, respectively (p=0.3). Overall, PCa with ISUP group ≥2 was detected at further biopsy in 2 (1%) and 3 (3.8%) patients in group 1 and 2, respectively (p=0.1). Basing on results of further prostatic biopsy, 4 (1.6%), 4 (1.6%) and 1 (0.4%) men underwent active surveillance, radical prostatectomy and radiotherapy during follow up, respectively, with no significant differences between the two groups.

Results: Overall, 449 (60.9%) and 288 (39.1%) patients underwent mpMRI at a Hub or Spoke center, respectively. Patients in the Hub group were more likely to have a prior negative biopsy (33 vs 20%) or be in active surveillance for PCa (16.3 vs 6.3%; all p≤0.001).

Significantly lower rate of PIRADS 3 lesions were reported in Spoke group compared to Hub group (36.1 vs 49%; p <0.001).

Patients in Spoke group reported a higher rate of transitional zone lesion compared to Hub group (23.6 vs. 9.4%; p < 0.001). Patients in the Hub group had higher detection rate for both any PCa (60.3 vs 48.1%) and csPCa (46.9 vs 38.7%; all p≤0.001). After stratifying for PI-RADS-v2 score, patients in Hub group had higher detection rate for PI-RADS-v2 score 3 (any PCa 43.6 vs. 28.2% p=0.008 csPCA 25.2 vs. 15.7% p=0.05) and PI-RADS-v2 score 4 (any PCa 74.7 vs.

55% csPCa 65.7 vs. 45.7% p<0.001) compared to patients in Spoke group. At multivariable analyses, mpMRI performed in a Spoke center was found to be an independent predictor for detection of csPCa at TB (OR 0.65; p =0.04)

Conclusions: Whether associated or not to SB, a negative TB can be considered as a reliable information for ruling out the presence of PCa at short-term follow up.

Conclusion: Our study shows that mpMRI performed in Hub centers provided a significantly higher PCa yield on TB. Dedicated radiologists are essential to avoid unnecessary and potentially harmful procedures.

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Short time delay between prostate biopsy for prostate cancer assessment and Holmium laser enucleation of the prostate (HoLEP) correlates with worse perioperative outcomes

Multi-omics analyses of feces identify discriminative signatures for radiotherapy-induced toxicity in prostate cancer patients: proof-ofconcept Willeke Danckaert, Ghent University Nora Sundahl, Mathieu Spaas, Valérie Fonteyne, Margot De Spiegeleer, Lynn Vanhaecke, Piet Ost

Lorenzo Bianchi, IRCCS Azienda Ospedaliero-Universitaria Policlinico di S. Orsola Pietro Piazza, Lorenzo Bianchi, Marco Giampaoli, Matteo Droghetti, Carlo Casablanca, Amelio Ercolino, Carlo Beretta, Dario Recenti, Eleonora Balestrazzi, Federica Farneti, Stefano Puliatti, Giuseppe Rosiello, Marco Amato, Daniele Romagnoli, Daniele D’Agostino, Caterina Gaudiano, Rita Golfieri

Introduction & Objectives: During radiotherapy (RT) for prostate cancer, part of the out-of-field dose is unintentionally delivered to the gastrointestinal (GI) organs, potentially leading to toxicity. It is hypothesized that patterns of disturbance in the GI microbiota composition, known as “dysbiosis”, may be a contributing factor. The aim of this study is to expand knowledge on the involvement of the patient’s microbiota composition and functionality in the pathophysiology of RT-induced GI toxicity.

Introduction & Objectives: Holmium Laser Enucleation of Prostate (HoLEP) is becoming the gold standard in treating lower urinary tract symptoms related to benign prostate enlargement.

To date, no data are available concerning the impact of time between a previous prostate biopsy (PB) to point out prostate cancer (PCa) diagnosis in patients at risk and HoLEP on perioperative outcomes. The aim of this study was to evaluate the impact of time from PB to HoLEP on perioperative outcomes.

Materials & Methods: As a proof-of-concept study, 20 prostate cancer patients with (n = 10) or without (n = 10) RTinduced toxicity (grade 1+ diarrhea as per common terminology criteria for adverse events v4.0) were selected from an ongoing prospective study (NCT04638049). Patients were either treated with prostate(bed) only RT (PBRT) (n = 16) or whole pelvis RT (WPRT) (n = 4). Fecal samples were longitudinally collected at 4 different time points. Bacterial fragments were amplified using 16S rRNA gene sequencing technology. Untargeted metabolic phenotyping was performed on an ultra-high-performance liquid chromatography hybrid high-resolution mass spectrometry (UHPLC-HRMS) platform.

Materials & Methods: We evaluated 172 patients treated with HoLEP within 12 months from a single previous PB at two European centers. Patients were stratified according to median time from PB to HoLEP (namely, ≤6 and >6 months). Differences between groups were investigated with Mann-Whitney U test and chi-square test to compare medians and proportions, respectively. Multivariate logistic regression was used to identify predictors of intraoperative complications. Linear regressions were used to test the association between time from PB to HoLEP and intraoperative complications, enucleation efficiency and enucleation time.

Results: The individual species (alpha) diversity of all patients significantly changed over time (p-value = 0.001). The community (beta) diversity diverged from the baseline profile during RT, but showed no significant difference when comparing dissimilarity indices between consecutive time points (p-value = 0.64).

However, a significant difference between the symptom groups was discovered (p-value = 0.001) but explained only 4.2% of the variability indicating substantial inter-individual variation. Based on the generated metabolic fingerprint, a natural patterning according to symptom classification was achieved through orthogonal partial least-squares discriminant analysis (OPLSDA) (Q²(Y) = 0.70; p-value = 4.58e-17) (Figure 1), with a total of 12 discriminating components detected. In addition, a good clustering according to RT treatment prescription (PBRT versus WPRT) was also observed (Q²(Y) = 0.68; p-value = 2.40e-16).

Results: Overall, 93 (54%) and 79 (46%) patients had PB ≤ 6 months and >6 months before HoLEP. Median enucleation time was significantly higher (60 vs 45 min) and median enucleation efficiency was significantly lower (0.8vs1.2) in men with PB≤6 months compared to those with PB>6 months (all p≤0.001). Patients with PB≤6months experienced higher rates of intraoperative complications (14%vs3%, p=0.04), significantly longer median in-hospital stay (2vs3 days, p<0.001) and median catheterization time (2vs3 days, p=0.04). No differences were found among the two groups in terms of functional outcomes at 12 and 24-months follow-up. At multivariable logistic regression, time between PB and HoLEP was independent predictor of intraoperative complications (OR 0.8, CI 0.6-0.9; p=0.006). Risk of intraoperative complications reduced by 1.5% (OR -1.5; CI -1.1-1.7, p=0.006; figure), efficiency of enucleation increased by 4.1% (OR 4.1; CI:2-6.2, p<0.001) and enucleation time reduced by 1.7 minutes for each month passed from PB to HoLEP (OR -1.7, CI -2.7-0.7, p=0.001).

Conclusion: Analysis of the fecal patterns of our pilot cohort revealed a distinctive signature between patients with and without radiation-induced toxicity. Both the characterization of the microbiota composition as well as a comprehensive UHPLCHRMS approach to assess the metabolic expression proved to be fit-for-purpose. In the near future, the aim is to analyze additional matrices – such as plasma and urine – and select the most discriminative biomarkers, which in turn may further expand our understanding of the mechanistic networks and boost the implementation of therapeutic strategies.

Conclusion: Time from PB to HoLEP ≤6 months is associated with higher risk of intraoperative complications, lower enucleation efficacy and longer enucleation time.

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Non-symptomatic patients Symptomatic patients

Non-symptomatic patients Symptomatic patients

KEYNOTE-365 Cohorts G and H: phase 1b/2 study of pembrolizumab + vibostolimab combination therapy in patients with adenocarcinoma metastatic castration-resistant prostate cancer or treatmentemergent neuroendocrine metastatic castration-resistant prostate cancer

Non-symptomatic patients

Figure 1 – Score plot of the OPLS-DA model using combined data from both the positive and negative ionization

Johann de Bono, The Institute of Cancer Research Neal D. Shore, Gero Kramer, Anthony Joshua, Xin Tong Li, Christian H. Poehlein, Charles Schloss, Evan Y. Yu

Symptomatic patients

mode after quality control normalization, logarithmic transformation and pareto scaling.

Figure 1 – Score plot of the OPLS-DA model using combined data from both the positive and negative ionization mode after quality control normalization, logarithmic transformation and pareto scaling.

Introduction & Objectives: Treatment options are limited for patients with metastatic castration-resistant prostate cancer (mCRPC) that progresses following treatment with nextgeneration hormonal agents (NHAs), such as enzalutamide and abiraterone acetate, or docetaxel. Approximately 20% of patients with adenocarcinoma mCRPC that progresses on androgen deprivation therapy develop treatment-emergent neuroendocrine mCRPC (t-NE), which shortens overall survival.

Pembrolizumab showed antitumor activity as monotherapy in docetaxel-pretreated patients with adenocarcinoma mCRPC in the phase 2 KEYNOTE-199 trial. The TIGIT inhibitor vibostolimab showed antitumor activity when combined with pembrolizumab in pretreated patients with several tumor types in a phase 1 dose escalation study. Combining PD-1 and TIGIT inhibition might have enhanced benefit in adenocarcinoma mCRPC and t-NE versus monotherapy. KEYNOTE-365 (NCT02861573) is a nonrandomized, open-label, multicohort, phase 1b/2 trial to evaluate the efficacy and safety of several pembrolizumab combination therapies in patients with mCRPC.

a from both the positive and negative ionization

ation and pareto scaling.

Materials & Methods: Patients enrolled in cohort G will have confirmed adenocarcinoma of the prostate without small cell histology per investigator. Cohort H will enroll patients with t-NE (≥1% neuroendocrine cells in a recent biopsy specimen confirmed by central histology review). Each cohort will include patients with prior docetaxel treatment for mCRPC. Prior treatment with ≤2 NHAs (for hormone-sensitive metastatic prostate cancer [mHSPC] or mCRPC) and 1 other chemotherapy for mCRPC is permitted. Additionally, enrollment in cohort H requires prostate cancer progression within <6 months of starting an NHA (for mHSPC or mCRPC) and within <6 cycles of docetaxel for mCRPC. Each cohort will enroll 40-100 patients with Eastern Cooperative Oncology group performance status score 0 or 1. Both cohorts will receive MK-7684A, a coformulation of pembrolizumab 200 mg and vibostolimab 200 mg, IV every 3 weeks (Q3W). Treatment will continue until disease progression, withdrawal of consent, or other discontinuation event. Adverse events (AEs) will be monitored throughout the trial up to 30 days after discontinuation (90 days for serious AEs) and graded using CTCAE v4.0. Imaging by computed tomography or magnetic resonance imaging will be performed at screening, then Q9W through week 54, and Q12W thereafter. Primary end points are safety and tolerability, prostate-specific antigen (PSA) response rate, and objective response rate (ORR) per RECIST v1.1 by blinded independent central review (BICR). Secondary end points include time to PSA progression; ORR and radiographic progression-free survival per Prostate Cancer Working Group 3 (PCWG3)-modified RECIST v1.1 by BICR; duration of response and disease control rate per RECIST v1.1 and PCWG3-modified RECIST v1.1 by BICR; and overall survival.

Results: KEYNOTE-365 is currently enrolling in Australia, Germany,

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Conclusion: Results from cohorts G and H of KEYNOTE-365 will provide a preliminary estimate of the efficacy and safety of pembrolizumab combined with vibostolimab in adenocarcinoma and t-NE mCRPC.

A phase 3, randomized, doubleblind trial of nivolumab or placebo combined with docetaxel for metastatic castration-resistant prostate cancer (CheckMate 7DX) Karim Fizazi, Gustave Roussy Michael Schweizer, Sumit K. Subudhi, Mark Linch, Cora N. Sternberg, Martin Boegemann, Chung-Wei Lee, Prabhu Bhagavatheeswaran, Fred Saad Introduction & Objectives: Treatment with docetaxel, a recommended first-line chemotherapy for metastatic castrationresistant prostate cancer (mCRPC), may enhance antitumor immune responses by (1) increasing neoantigen presentation, (2) stimulating proinflammatory cytokine secretion, and (3) downregulating suppressive immune cell populations.

Immunotherapy may augment these effects, providing a strong rationale for combining immune checkpoint blockade with docetaxel in patients with mCRPC. In support of this hypothesis, final results from the phase 2 CheckMate 9KD trial showed encouraging clinical activity of a combination of the anti– programmed death-1 antibody nivolumab and docetaxel in patients with chemotherapy-naïve mCRPC (Fizazi K et al. J Clin Oncol 2021;39[suppl 6]:12). In this randomized, double-blind phase 3 trial (CheckMate 7DX), we will evaluate the combination of nivolumab plus docetaxel versus placebo plus docetaxel for men with mCRPC (NCT04100018).

Materials & Methods: Key inclusion criteria are histologically confirmed adenocarcinoma of the prostate with current evidence of metastatic disease, Eastern Cooperative Oncology Group performance status 0–1, ongoing androgen deprivation therapy with a gonadotropin-releasing hormone analogue or bilateral orchiectomy, documented progression per Prostate Cancer Working Group 3 (PCWG3) criteria within 6 months before screening, no prior chemotherapy in the mCRPC setting, 1–2 prior novel hormonal therapies (eg, abiraterone, enzalutamide, apalutamide, or darolutamide) in the recurrent nonmetastatic and/or metastatic setting (only 1 prior novel hormonal therapy is allowed in the mCRPC setting), and available tumor tissue for biomarker analysis. Key exclusion criteria are active brain metastases, conditions requiring systemic corticosteroid/ immunosuppressive treatment within 14 days of start of study treatment, autoimmune disease, and prior treatment targeting T-cell co-stimulation or checkpoint pathways. Patients are randomized 1:1 to nivolumab plus docetaxel (arm A) or placebo plus docetaxel (arm B), followed by nivolumab monotherapy (arm A) or placebo alone (arm B). Docetaxel will be administered for a maximum of 10 cycles; nivolumab will be administered for a maximum of 2 years. Primary endpoints are radiographic progression-free survival by blinded independent central review per PCWG3 criteria and overall survival. Secondary endpoints include objective response rate and time to and duration of objective response per PCWG3, prostate-specific antigen response rate, time to prostate-specific antigen progression, safety/tolerability, and time to pain progression (assessed by the Brief Pain Inventory-Short Form). Enrollment is ongoing with a target of 984 randomized patients.

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Surgery for pathological T3a, T3b, and lymph node positive, prostate cancer: surgical, functional, and oncological outcomes

Surgical treatments of benign prostatic hyperplasia and prostate cancer stereotactic body radiotherapy: impact on long-term toxicity

Niall Gilliland, James Cook University Hospital Anthony Koupparis

Constance Huck, University Hospital of Geneva Vérane Achard, Thomas Zilli

Introduction & Objectives: To investigate and document the surgical, functional and oncological outcomes following surgery for high risk prostate cancer patients.

Introduction & Objectives: Prostate cancer (PCa) patients with a prior history of TURP or adenomectomy are at higher risk to develop genitourinary (GU) toxicity after conventional fractionated radiotherapy. As data on safety of SBRT are scarce in this setting, aim of this study is to report on the impact of previous surgical treatments of benign prostatic hyperplasia on GU toxicity after SBRT for localized PCa.

Materials & Methods: Patients with pathological T3a, T3b and N1 disease were extracted from our prospectively updated institutional database. Data included demographics, preoperative cancer parameters, short and long term complications, and functional results. Details of biochemical recurrence, type, and oncological outcomes of salvage treatments, cancer specific and overall survival were also obtained.

Materials & Methods: Among 150 prostate SBRT (36.25 Gy or 40 Gy in 5 fx) realized from 2014 to 2019 in a single institution, data of 26 men (median age 76 years) with a history of TURP (n=21) or adenomectomy (n=5) were analyzed. Repeated TURP were performed in 3 patients, with a median time between surgery and SBRT of 54 months (range, 2-204). GU toxicity was evaluated using the CTCAE v4.0 scale.

Results: A total of 669 patients were included; 58.9% had T3a disease, 35.9% had T3b, and 11.4% had N1 disease. With a median follow up of 66 months (8-129), overall survival was 94.3%, cancer specific survival was 98.7%, and biochemical recurrence was 45.6%. Average inpatient stay was one day, and the overall complication rate was 9.1%; 54.2% experienced a biochemical recurrence and 90.3% went on to have one or more salvage treatments, which were varied. Significant predictors of biochemical recurrence included pathological stage, any positive margin, and patient age (p<0.05). A total of 44.9% of patienst had an immediate biochemical recurrence, with 90% receiving subsequent treatment, and 20.5% of those having a durable response. None of the patients who had biochemical recurrence, that received salvage prostate bed radiotherapy alone had a durable biochemical response. 54% of patients had delayed biochemical recurrence with 63.5% receiving subsequent treatment, of which, 44% had a durable response. Those with a durable response to salvage treatment, had systemic treatments such as hormone therapy.

Results: With a median follow-up of 45 months (range, 19-87), 11 out of 26 (42%) patients experienced at least one episode of transient hematuria. One patient (3.8%) with 3 previous TURP presented a grade 3 acute non-infective cystitis. Late grade 2 and 3 GU toxicities were observed in 10 (38.5%) and 4 patients (2 treated with adenomectomy, 1 with multiple TURP, and one with a 140cc prostate size, 15.4%), respectively, with no grade 4 or 5 adverse events. Necrotic tissue in the surgical defect was observed at cystoscopy in the 5 patients with Grade 3 GU toxicity.

A significant recovery of GU symptoms was observed for all 5 patients after hyperbaric oxygen therapy.

Conclusion: Prostate SBRT is feasible and well-tolerated in patients with a medical history of surgical treatments of benign hyperplasia. Patients with prior adenomectomy or multiple TURP are at higher risk to develop grade 3 GU toxicity and should be carefully evaluated before SBRT treatments.

Conclusion: Surgery in locally advanced high risk prostate cancer is associated with encouraging surgical and functional outcomes, cancer specific survival, and overall survival rates in these patients. Pathological stage is a significant predictor of biochemical recurrence. The present analysis shows that long term observation for certain patients with biochemical recurrence is appropriate, and questions the effectiveness of further local salvage treatment in patients with immediate biochemical recurrence post operatively. This is due to the likely micro-metastatic disease present in this cohort of patients.

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How far can we trust prostate mpMRI for T3 disease – Real-life experience

Is age a limiting factor for radical prostatectomy?

Luísa Jerónimo Alves, Hospital Beatriz Ângelo Gabriel dos Anjos, Kris Maes

Luísa Jerónimo Alves, Hospital Beatriz Ângelo Gabriel dos Anjos, Adalgisa Guerra, Jaime Calha, Kris Maes

Introduction & Objectives: Prostate cancer is the second most common male cancer in the world, and is currently the second cause of malignancy-related decease in the USA and Europe.

Patient and tumour features are usually taken into account to choose the best treatment approach. Age is still a matter of debate when selecting the best candidates for surgery. The aim of our study is to analyse continence rate in patients over 70 yearsage after robotic radical prostatectomy (RARP).

Introduction & Objectives: Extracapsular extension (ECE) and seminal vesical invasion (SVI) of prostate cancer are poor prognostic factors related to progression after treatment and worse overall survival. Preoperative accurate staging of T3 disease is of the utmost importance to correctly stratify risk and to plan the surgery, particularly, in neurovascular bundle sparing (NVB) procedures. Prostate multiparametric-magnetic resonance imaging (mpMRI) proved to be superior to digital rectal exam in defining preoperative T stage. The aim of our study is to analyse the sensibility of preoperative prostate mpMRI for detection of T3 disease amongst patients submitted to robotic-assisted radical prostatectomy (RARP) in our institution.

Material & Methods: We retrospectively evaluated 64 patients over 70 years-age, and 64 patients with ages between 60 and 70 years-old undergoing RARP from 2015 to 2020, in our institution.

Preoperative factors (Body mass index (BMI), PSA, ISUP grade, prostatic volume, previous transurethral resection of the prostate (TURP)), histopathological results and continence outcomes were evaluated. Postoperative continence was defined as 0 or 1 pad for protection. Statistical analysis was performed with the use of SPSS version 24.

Material & Methods: We retrospectively evaluated 99 patients with T3 disease, imagological (iT3) or on radical prostatectomy specimen (pT3), from 2015 to 2021, in our institution. All lesions classified as indeterminate (iT2i) at mpMRI were excluded. mpMRI images were acquired with either on a 1.5 or a 3T scanner and were all reviewed by two experienced radiologists. Statistical analysis was performed with the use of SPSS version 24.

Results: Median age in the group>70 was 73.1 years (range 7080 years) and in the group 60-70 was 64.9 years (range 60-70). No statistically significant differences were observed for preoperative PSA, BMI or prostatic volume with median values of 7.3 vs. 6.6 ng/ mL, 25.3 vs. 27.2 kg/m2 and 49 vs. 51 cc, respectively. Previous TURP was registered in 4 patients in group>70 and in 2 patients in group 60-70. A bilateral nerve-sparing procedure was performed in 67.2% of older group and in 84.4% of patients of the group 60-70. Urinary continence was evaluated at month 1, 3,6 and 12.

In the group>70 continence rates were 29.6%, 72.2%, 87.0% and 94.4% comparing to continence rates of the group 60-70, 74.5%, 96.4%, 96.4%, 98.2%, respectively. Previous TRUP was associated with worse rates of continence (p=0,035). BMI, ISUP grade, prostatic volume and nerve-sparing procedure did not show statistical difference regarding urinary continence (p>0,05).

Results: Median age was 63.3 (range 42-79) years. The median PSA at diagnosis was 7.6 (Interquartile range 5.5-10.5) ng/mL. Thirty-nine patients (39%) were gleason 8 or higher, 46 (46,5%) and 19 (19%) patients were classified iT3a and iT3b, respectively.

On final pathology, 22 patients had SVI (pT3b). Overall prostate mpMRI sensitivity and positive predictive value for detection of T3 were 53% and 70%, respectively. On subgroup analysis, in patients with pT3b prostate cancer prostate mpMRI sensitivity was 77%.

Conclusion: mpMRI is a valuable preoperative assessment tool for detailed anatomical information providing prognostic data and allowing surgeons to best plan the procedures. While mpMRI alone outperformed Partin tables in the detection of T3 stage and prediction of organ-confined disease, its overall sensitivity for T3 is poor. This limitation should be taken into account when considering NVB procedures. Moreover, currently, lymph node invasion nomograms combine clinical and mpMRI information to select the best candidates for lymphadenectomy which raises the question if we might be under/overtreating patients based on T3 stage on mpMRI. This low overall sensitivity could be explained by the low detection rate of microscopic ECE on mpMRI.

Conclusion: Our results suggest that robotic radical prostatectomy represents a feasible option to treat prostate cancer in older patients. Nevertheless, patients over 70 years-old had worse early continence rates and slightly inferior results at 12 month of follow-up that might be explained by the higher rate of previous TRUP. Careful patient selection and counselling is crucial before offering a surgical approach in elderly. However, in our opinion, patients should not be precluded from a curative treatment solely based on their age.

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Influence of ASAP on Gleason score in subsequent prostate biopsies

Repercussion on biochemical recurrence in understaging prostate biopsy

Marta Jiménez Navarro, University Hospital Nuestra Señora de la Candelaria Carrion Valencia Almudena, Lorena García, Sara González Nieto, Lara Torres León, Raquel Clemente Graffigna, Jonathan Rodríguez Talavera, Jesus Monllor Gisbert

Marta Jiménez Navarro, University Hospital Nuestra Señora de la Candelaria Carrion Valencia Almudena, Lorena García, Sara González Nieto, Lara Torres León, Raquel Clemente Graffigna, Jonathan Rodríguez Talavera, Jesus Monllor Gisbert

Introduction & Objectives: Prostate cancer (CaP) is the most common solid tumor in men. Atypical small acinar proliferation (ASAP) occurs in up to 5% of prostate biopsies, and 30-50% will progress to CaP in subsequent biopsies. Existing data on the pathological characteristics of PCa identified after an initial ASAP diagnosis are conflicting (some studies have observed a predominance of low-risk PCa, and others have found a higher incidence of clinically significant PCa).

Introduction & Objectives: Radical prostatectomy remains the standard treatment option in organ-confined prostate cancer. The diagnosis is obtained previously performing a prostate biopsy. In the literature is described great variability in the understaging of the biopsy compared to the radical prostatectomy specimen.

The objective is to analyze the percentage of prostate biopsy understaging versus the radical prostatectomy specimen in our center and to assess the repercussion in terms of biochemical recurrence of the group with biopsy and concordant piece, compared to understaged biopsy.

Analyze the relative risk of the presence of ASAP to develop CaP, and the influence of it presence on the Gleason Score.

Materials & Methods: Retrospective cohort study, incuding patients undergoing prostate biopsy for one year in our center, to calculate the relative risk of ASAP for PCa, both groups being comparable in the mean value of PSA (allowing a possible difference of 1 point) and in digital rectal examination (coincident).

Nonparametric tests were used to analyze the impact of ASAP on the Gleason grade.

Materials & Methods: Retrospective study of all patients underwent radical prostatectomy consecutively in our center from February 2017 to December 2018. The inclusion criteria were a diagnosis of prostate adenocarcinoma by transrectal biopsy and a minimum of 13 months of follow-up. The statistical analysis is performed with SPSS v.22 program.

Results: 82 patients with a mean age of 62 years were included.

The concordance ratio between biopsy and surgical specimen was 39%, 45% understage, 16% suprastage. The greatest difference in under-staging was obtained for the group of ISUP 1 in biopsy: 41% were restated to ISUP 2 after surgery, and 24% to ISUP 3.

Comparing the biochemical recurrence between the concordant group and the understaged group, no differences were obtained.

No differences were found in time (in months) to biochemical recurrence between both groups (12-month concordance group; understaged group: 16 months. T student p = 0.37).

Results: During October 2016 to October 2017, 441 prostate biopsies were performed. 52 (12%) were diagnostic of ASAP. Mean age was 65 years, mean PSA value was 6,67 ng / dl and digital rectal examination was suspicious in 30% of cases.

The indication for biopsy in 88% of the cases was PSA elevation, while in 11% a suspicious rectal examination. 19% obtained a synchronous diagnosis of ASAP + CaP, 27% lost follow-up, and 64% underwent a second prostate biopsy in a medium period of 8.7 months (3-37), being diagnostic for PCa in 9 cases (32%).

The relative risk of ASAP for CaP was 1,28. In the first biopsy, there were no statistically significant differences in the Gleason Score between patients with a synchronous diagnosis of ASAP compared to patients with not synchronous ASAP (MannWhitney U test: p = 0.798) (No ASAP. Gleason 6 : n = 9; Gleason 7: n = 3 / ASAP. Gleason 6: n = 7; Gleason 7: n = 3).

Conclusion: In our center, under-reporting is estimated around 45%, similar to some of published series. No differences were found in terms of impact of this underestimation on the biochemical recurrence or the time until it. A greater number of patients is required to validate our results.

In the second biopsy, no differences were obtained in Gleason Score between patients with prior ASAP compared to patients with not prior ASAP (Mann-Whitney U test: p = 0.072) (No ASAP. Gleason 6: n = 4; Gleason 7: n = 2 / ASAP. Gleason 6: n = 7; Gleason 7: n = 0).

Conclusion: In our study, the prevalence of ASAP is slightly higher than that published in the literature and is a risk factor for PCa (RR = 1.28). With the results of our study, we cannot affirm that the history of ASAP influences the Gleason Score, although to validate our findings, a larger sample would be necessary.

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Extension of positive surgical margins after radical prostatectomy: does size matter? – A systematic review and meta-analysis

KEYNOTE-365 Cohorts E and F: phase 1b/2 study of pembrolizumab + lenvatinib combination therapy in patients with adenocarcinoma metastatic castration-resistant prostate cancer (mCRPC) or treatment-emergent neuroendocrine mCRPC (t-NE)

Athul John, University of Adelaide Rick Catterwell, Luke Selth, Michael O'Callaghan Introduction & Objectives: The relevance of positive surgical margins (PSM) in prostate cancer patients undergoing radical prostatectomy (RP) remains controversial, given that its prognostic capacity for biochemical recurrence (BCR) and other outcomes is inconsistent. Over the last decade, several studies have explored the extension of PSM and its ability to predict BCR. Hence, we aimed to review and perform a meta-analysis of studies investigating the role of extent of PSM after RP in predicting BCR and oncological outcomes.

Gero Kramer, Medical University of Vienna Neal D. Shore, Anthony Joshua, Xin Tong Li, Christian H. Poehlein, Charles Schloss, Johann de Bono, Evan Y. Yu Introduction & Objectives: Docetaxel or the next-generation hormonal agents (NHAs) abiraterone and enzalutamide are the standard of care for patients with adenocarcinoma mCRPC but are not curative. Approximately 20% of patients develop t-NE after treatment for adenocarcinoma mCRPC, which is associated with shorter survival and has no standard of care. The vascular endothelial growth factor (VEGF)/fibroblast growth factor receptor (FGFR) inhibitor lenvatinib inhibits proliferation and angiogenesis in adenocarcinoma prostate cancer cells in vitro and in mice. In the phase 2 KEYNOTE-199 trial, pembrolizumab monotherapy showed promising antitumor activity in docetaxel-pretreated patients with adenocarcinoma mCRPC. VEGF/FGFR inhibition combined with PD-1 inhibition may have enhanced benefit in adenocarcinoma mCRPC and, in addition, may provide a new treatment option for t-NE mCRPC.

Materials & Methods: A systematic search was conducted using MEDLINE, Embase and Cochrane databases according to Preferred Reporting Items for Systematic Reviews and Metaanalysis (PRISMA) guidelines. The quality of the studies selected was assessed and a protocol was registered prior (PROSPERO: CRD42020195908). The primary outcome measure was BCR. Secondary outcome measures included cancer-specific and metastasis-free survival. Given the differences in analysis used across studies, subgroup meta-analysis was performed using the multivariable hazard ratio based on the various margin thresholds and statistical analysis undertaken (Continuous, <1 mm vs >1 mm, >3 mm v <3 mm).

Materials & Methods: KEYNOTE-365 (NCT02861573) is a nonrandomized, open-label, multicohort, phase 1b/2 trial conducted to evaluate different pembrolizumab combination therapies in several patient populations with mCRPC. Cohort E will enroll patients with confirmed adenocarcinoma of the prostate without small cell histology per investigator. Cohort F will enroll patients with t-NE (≥1% neuroendocrine cells in a recent biopsy specimen confirmed by central histology review). Each cohort will include patients with prior docetaxel treatment for mCRPC. Prior treatment with ≤2 NHAs (for hormone-sensitive metastatic prostate cancer [mHSPC] or mCRPC) and 1 other chemotherapy for mCRPC is permitted. Additionally, enrollment in cohort F requires prostate cancer progression within <6 months of starting an NHA (for mHSPC or mCRPC) and within <6 cycles of docetaxel for mCRPC. Each cohort will enroll 40-100 patients with Eastern Cooperative Oncology Group performance status score of 0 or 1. Both cohorts will receive pembrolizumab 200 mg IV every 3 weeks (Q3W) + oral lenvatinib 20 mg once daily until disease progression, withdrawal of consent, prespecified alanine aminotransaminase or aspartate aminotransaminase elevation, or other discontinuation event. CT or MRI will be performed at screening, Q9W through week 54, and Q12W thereafter. Adverse events (AEs) will be monitored throughout the trial through 30 days after discontinuation (90 days for serious AEs), graded using the CTCAE v4.0. Primary end points are safety and tolerability, prostatespecific antigen (PSA) response rate, and objective response rate (ORR) per RECIST v1.1 by blinded independent central review (BICR).

Secondary end points include time to PSA progression; ORR and radiographic progression-free survival per Prostate Cancer Working Group 3 (PCWG3)-modified RECIST v1.1 by BICR; duration of response and disease control rate per RECIST v1.1 and PCWG3-modified RECIST v1.1 by BICR; and overall survival.

Results: The systematic search yielded 4186 results; 18 studies were included for meta-analysis. The sample sizes varied from 117-579. The average follow-up period ranged from 1.6 -7.1 years.

PSM extension (continuous) of PSM was predictive of BCR (nine studies, HR 1.05 (CI 1.02 – 1.07), p <0.05). PSM extension greater than 1 mm was associated with BCR compared to less than 1mm (three studies HR 1.97 (1.26 – 3.07) p<0.05). PSM extension greater than 3 mm was associated with BCR compared to less than 3mm (six studies, HR 2.08 (1.33-3.25), p<0.05)).

Conclusion: Extension of PSM is prognostic for BCR in patients after RP. Further long term studies are needed to estimate the impact of these variables on cancer specific outcomes such as systemic progression and mortality, and to identify a low risk threshold.

Results: KEYNOTE-365 is currently enrolling in Australia, Germany, New Zealand, Spain, and the United States.

Conclusion: Results from cohorts E and F of KEYNOTE-365 will provide a preliminary estimate of the efficacy and safety of pembrolizumab combined with lenvatinib in adenocarcinoma and t-NE mCRPC. 16

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Most patients are symptomatic before treatment with external beam therapy for prostate cancer

Non-invasive prognosis of prostate cancer using deep learning on MRI Luna Maris, Ghent University Maarten Larmuseau, Milan Decuyper, Roel Van Holen, Kathleen Marchal, Kim Van der Eecken, Piet Ost

Miikka Lehtonen, Tampere University Jorma Sormunen, Pirkko-Liisa Kellokumpu-Lehtinen

Introduction & Objectives: In current medical practice, invasive procedures are necessary to define the prognosis for patients with prostate cancer (PCa). Grading of PCa relies on tissue biopsy to determine the Gleason score, where a score of at least 7 indicates clinically significant PCa (csPCa). Despite multiparametric MRI (mpMRI) being increasingly used for noninvasive detection of csPCa, many men still undergo unnecessary biopsy as the interpretation of these scans remains time consuming and challenging. In this work, a computer system is developed that automatically defines the presence of csPCa from mpMRI, including T2, ADC and KTrans sequences.

Introduction & Objectives: In our retrospective study, we found out that both worse Charlson Comorbidity Index score and WHO score weaken the overall survival after EBRT for PC, but not prostate cancer specific survival, metastasis-free survival or biochemical recurrence-free survival (Lehtonen et al. BMC Cancer.

2020 ;20(1):1–8). We also made a thorough analysis, what kind of symptoms patients had before diagnosis and those are reported here.

Materials & Methods: A total of 665 patients who underwent EBRT for PC in Tampere University Hospital between 2008 and 2013 were included in the study. Exclusion criteria included previous failed pharmaceutical or surgical treatment or metastatic disease, among others. Data were gathered from patient records before diagnosis retrospectively.

Materials & Methods: The developed computer system is based on two deep learning models. Firstly, a 3D UNet segments the prostate in T2-weighted MRI. Two independent public data sets, Prostate-MRI-US-Biopsy and PROSTATEx, were used to train and validate the model, respectively. Both data sets contain expert annotations of the prostate that were used as true labels.

Automatic prostate segmentation allows to reduce the mpMRI to the prostate region, but also has applications in radiology and radiotherapy. Afterwards, a second model classifies the reduced images according to the presence of csPCa. A 3D ResNet was trained on different combinations of MRI sequences. The PROSTATEx data set, which contains mpMRI linked to the true presence of csPCa, was split into a train and validation set for this task. Additional independent data was provided by the Ghent University Hospital (UH) to further validate both models.

Results: Median age at the time of diagnosis was 70.9 years (range: 46.1-89.0). Most patients were symptomatic (N=389, 58.4 %). The most common symptoms were weak urinary flow (N=166, 24.9 %), nocturia (defined as >2 micturitions per night, N=154, 23.1 %) and frequent urination during daytime (N=146, 21.9 %). Lower abdominal pain was reported by 42 patients (6.3 %). Sexual symptoms were rare, but erectile dysfunction was only considered as a symptom if it had occurred within two years prior to diagnosis (Figure 1).

Conclusion: Most patients who were treated with EBRT for PC in Finland were symptomatic, even though the asymptomatic patients were also common. There was also a large PSA screening study (ERSPC) in the Tampere region for 55-67-year-old men until 2007, which may contribute to the abundance of asymptomatic cases. When symptoms of PC occur, they mostly resemble those met in benign prostatic hyperplasia.

Results: Mean Dice similarity coefficients (DSCs) of 0.90 and 0.76 were found when validating the UNet for prostate segmentation on the PROSTATEx data and the data from the Ghent UH, respectively. These DSCs indicate a good match with expert annotations. The ResNet obtained the best performance when predicting the presence of csPCa based on the combination of T2 with ADC. A ROC-AUC of 0.83 and a PR-AUC of 0.73 were reached on the validation set of PROSTATEx. When including additional independent data from the Ghent UH in the validation set, a ROCAUC of 0.86 and a PR-AUC of 0.88 were found.

Conclusion: This work shows that deep learning can be applied to mpMRI to predict prognostic indicators for PCa patients, such as the presence of csPCa. Both the segmentation and classification models achieve a performance that is comparable to the current standard of care but are fully automatic and can produce results within seconds. This work takes a first step towards automatic, fast, accurate and non-invasive PCa prognosis. As deep learning models critically depend on the size of the data set, including more patients in the study is expected to further improve the results.

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Preliminary results of acute and early toxicity and biochemical response of an hypofractionated schedule for localized prostate cancer: our road to extreme hypofractionation Joel Mases Rosinés, Hospital Clinic of Barcelona Franc Pagan, Diego Muñoz-Guglielmetti, Pablo Arranz, Gabriela Oses, Elisabet Escudero, Cristina Castro, Carla Cases, Jordi Saez, Francesc Casas, Meritxell Mollà Introduction & Objectives: Moderate hypofractionation (2.2 – 3.5Gy per fraction) has become the gold standard for radiotherapy (RT) of localized prostate cancer (LPC). It has been widely proved that hypofractionated regimes (HF) are equivalent in terms of biochemical control and toxicity to normofractionated ones. We designed in our center a prospective study to evaluate a regime of RT to the prostate (+/- seminal vesicles) in LPC with a higher dose per fraction (4Gy) than most usual HF schemes, closer to extreme hypofractionation, up to a dose of 56Gy in 14 fractions (EQD2 88Gy). We present the preliminary results of acute and early (at 6 weeks) gastrointestinal (GI) and genitourinary (GU) toxicity and biochemical response (BR).

Materials & Methods: From July 2019 to June 2021, 74 patients with stages T1c-T3aN0M0 were included. No elective nodal irradiation was allowed. Median age at diagnosis was 77 (51-89).

Median Charlson Comorbidity Index (CCI) was 4 (1-8). Initial mean PSA was 8.73 (3.25-24). 18.9% (14) were low risk, 21.6% (16) were favorable intermediate, 24.3% (18) unfavorable intermediate (UIR) and 35.1% (26) high (HR). Mean Roach score for microscopic lymph node disease was 14.45% (1-42).

Androgen deprivation therapy (ADT) was given to UIR and HR patients (60.8%), with a median neoadjuvancy of 5 months (3-12), and a mean PSA previous to RT of 0.72 (0.05 – 3.01) for those receiving ADT. 6 patients (8.1%) had previous transurethral resection (TRUS) and 2 (2.7%) previous adenectomy.

A total dose of 56Gy was given, in alternating twice and thrice weekly fractions for 5 weeks. Median overall treatment time (OTT) was 37 days. Acute and late toxicity was evaluated using the RTOG toxicity scale. PSA was evaluated at 6 weeks and every 6 months. Data was analyzed with SPSS v25.

Results: With a median follow up of 8 months (1-24), 2 patients died from other causes, and 1 patient was lost to follow up. 2 treatment discontinuations at respectively 20 and 8Gy occurred, 1 because of severe COVID infection and 1 because of acute G3 GU toxicity (1.3%) which required urinary catheter and refused continuation. Acute GU G1 and G2 toxicities were 28.8 and 42.5%; and 22.5 and 29.6% at 6 weeks. Acute G1-2 GI toxicity was 20.5%, with only 5.6% G1 at 6 weeks. There were no differences in acute GU toxicity regarding ADT (p=0.73), TRUS (p=0.63) or prostate volume (p=0.43), nor acute GI toxicity differences regarding ADT (p=0.98). Mean PSA at 6 weeks was 2.44 for patients with no ADT and 0.21 with ADT. Conclusion: HF treatment for LPC at 4Gy per fraction is well tolerated with low and transient acute toxicity and good early BR. Longer follow up is needed to evaluate late toxicity and biochemical control.

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Outcomes and pattern of relapse after SABR for oligometastatic prostate cancer Carole Mercier, Iridium Netwerk Charlotte Billiet, Ines Joye, Tom Van den Mooter, Michiel Strijbos, Piet Ost, Piet Dirix Introduction & Objectives: The addition of stereotactic ablative radiation therapy (SABR) to standard of care for patients with oligometastatic prostate cancer has the potential of improving survival and delaying further metastases. The primary aim of this analysis is to report survival outcomes of patients with hormonesensitive (HSPC) and castrate resistant (CRPC) oligometastatic prostate cancer treated with SABR. Pattern of relapse was also analysed.

Materials & Methods: This is a single-centre retrospective study of patients with oligometastatic prostate cancer treated in Iridium Network between 2014 and 2018. All patients with oligometastatic (≤3 active lesions) HSPC and CRPC treated with SABR were included. Patients could have received concomitant androgen deprivation therapy (ADT) with SABR. Metastatic lesions could be diagnosed on conventional (bone scintigraphy or CT) or innovative (magnetic resonance imaging; choline or prostate specific membrane antigen (PSMA) PET-CT) imaging techniques. Data were collected using electronic records. KaplanMeier survivor function and log rank test were used to calculate biochemical progression-free survival (bPFS), distant progressionfree survival (dPFS), and overall survival (OS).

Results: Eighty-seven men received SABR to 114 metastases.

Nineteen patients were castrate resistant and 68 patients hormone-sensitive at the time of SABR. The majority of patients (61/87; 70%) had a single metastasis, 23/87 (26%) patients were treated for 2 lesions and 3/87 (4%) patients had 3 metastases. In 13/87 (15%) patients, the treated lesions were pelvic lymph nodes; the remaining patients received SABR for extrapelvic lymph nodes or bone metastases. ADT was administered concomitantly with SABR to 56 patients (64%), while 31 (36%) did not receive ADT. To diagnose OMD, innovative imaging techniques were applied for 67 (77%) patients, and for 20 (23%) patients conventional imaging techniques were used.

Median follow-up was 42 months. In 22 (25%) patients, no decline from baseline PSA was recorded. Best PSA-response is presented in Figure 1. Median bPFS was 12 months in hormone-sensitive patients as well as in castrate-resistant patients. Median dPFS was 22 versus 18 months for HSPC versus CRPC, respectively (p = 0,02; Figure 2). Median OS was 73 months for hormonesensitive patients and not reached for castrate-resistant patients.

Information on pattern of relapse was retrieved for 79 patients: 36/79 (45%) patients were long-term disease-free (>18 months), 22/79 (28%) patients were oligoprogressive (≤3 new lesions) and 21/79 (27%) patients developed a polymetastatic relapse.

Conclusion: In this cohort, patients with hormone-sensitive oligometastatic disease showed potential benefit from SABR with a median dPFS of 22 months. Well-selected patients with oligometastatic CRPC may also benefit from SABR. Overall, 36/87 (41%) of patients were still free from clinical relapse at 18 months.

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Outcomes of upfront docetaxel with androgen deprivation therapy in patients with metastatic hormonenaïve prostate cancer: experience of a Portuguese Center

No decision about me without me: assessing informed consent practices prior to surgery for prostate cancer and benign prostatic hypertrophy Ciarán O'Hanlon, GKT School of Medical Education, King's College London

Lúcia Moreira Gil, Centro Hospitalar de Lisboa Central Ana Filipa Reis, Ana Sofia Chantre Spencer, Diana Simão, Mariana Sardinha, Chiara Rodriguez, Ricardo Jorge Martins Da Luz

Introduction & Objectives: Sub-optimal provision of informed consent to patients is widely reported across multiple surgical specialties, as is poor retention of information by patients regarding surgical complications. The aim of this study, was to evaluate how informed, patients undergoing prostate surgery, perceive themselves to be about the risk of associated complications pre-operatively. Furthermore, this study aimed to assess for any significant differences between patients undergoing surgery for prostate cancer (Pca) versus Benign Prostatic Hyperplasia (BPH).

Introduction & Objectives: Upfront Docetaxel chemotherapy became the standard of care for mHSPC, based on the clinical trials CHAARTED and STAMPEDE. We sought to evaluate our clinical experience and outcomes in the group of patients with mHNPC who received Docetaxel upfront with ADT.

Materials & Methods: This was a prospective cross-sectional study using quantitative methods. Electronic surveys were administered at a standardised time point, the surgical preassessment consultation prior to surgery. Patients used a modified 3 point likert scale to rate how informed they felt about the risk of 8 peri-operative complications occurring (table 1).

Patients selected from the following options: 1. Not informed at all 2. Discussed but would like more information 3. Sufficiently informed. The study was conducted across 4 tertiary hospital sites. A Mann-Whitney U test was used to test for differences between treatment groups.

Materials & Methods: A retrospective analysis of 26 patients with HVD mHSPC as per CHAARTED criteria treated with ADT and upfront Docetaxel 75 mg/m2from July 2017 to May 2021.

Progression was defined according to the PCWG-3 criteria. The PFS was calculated as time from start of treatment to the date of progression. OS and PFS was analysed by Kaplan-Meier estimates and log-rank test. Rates of febrile neutropenia (FN) was also evaluated.

Results: The median age was 63 (range:44-81) years. At a median follow-up of 42mo, the mOS was 27mo and the mPFS was 8mo.

In the patients with ADT plus Docetaxel, 38%(n=10) patients achieved a PSA level≤0.2ng/mL. The PSA nadir≤0.2ng/mL was achieved in 19%(n=5) of patients after 6mo of treatment and in 19%(n=5) after 12mo. The minimum PSA nadir and the median time to PSA nadir were <0,05ng/mL (7patients) and 9mo. In this setting, 15%(n=4) patients had AE of grade≥3, 4 neutropenias, of which 3 FN(11%) with 1 also associated with G4 diarrhea and 1 G3 neutropenia. G4 toxicities were described in 3 patients, which led to the interruption of treatment. Secondary prophylaxis with G-CSF was performed in only 1 patient after delays treatment, 3 times followed by prolonged G3/G2 neutropenia and he completed the 6cycles without dose reduction. None of the patients had primary prophylaxis with G-CSF. 88%(n=23) completed 6 cycles of Docetaxel, with 4% requiring dose reductions. 81%(n=21) developed CRPC within 1 yr and the median time to the development CRPC was 8mo. Overall, of the 58%(15) patients who progressed within 6mo of completing Docetaxel, 1 had Cabazitaxel as the next treatment. The remaining 14 patients were treated with ART as the next treatment, 8 progressed within 6mo with mPFS on 2ndline of 3.3mo and were treated with Cabazitaxel. Of those treated with cabazitaxel in 3rd line, 6 progressed with a mPFS 3.9mo. 54%(n=14) were alive at the last follow-up.

Results: 48 patients consisting of 33 Pca and 15 BPH patients were included for analysis. 32/33 Pca patients underwent Robot Assisted Radical Prostatectomy (RARLP) and 1 underwent TURP. 11/15 BPH patients underwent Photoselective Vaporisation of the Prostate (PvP), 4/15 TURP and 1 Holmium Laser Enucleation of the Prostate (HoLEP). Results are summarised in table 1. Subgroup analysis of BPH cases found no significant inter-procedure differences.

Conclusion: Patients undergoing surgery for BPH felt inadequately informed pre-operatively about key complications.

Patients undergoing surgery for Pca were significantly better informed. Further research and a larger sample size is required to help account for inter-site variability.

Conclusion: Upfront Docetaxel is reasonably well tolerated and the chemotherapy regimen with Docetaxel alone has a risk of FN<10%. However, in this study, patients who had FN had characteristics that conferred high risk, according to the EORTC guidelines for the use of G-CSF. In patients who progress within 6mo of completing Docetaxel, ART may not be the optimal sequencing therapeutic. Further prospective research is warranted in order to guide treatment sequencing. Upfront Docetaxel achieved good biochemical and clinical responses but not sustained over time and had limited PFS. However, the shortterm outcomes were limited and longer follow-up is needed.

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Table 1: Comparison of informed consent regarding surgical complications in Pca and BPH patients. P < .05 indicates significant difference between groups.

Complication

Not informed at Discussed but all

Sufficiently

Cognitive impairment and brain morphological and functional features in prostate cancer patients treated with androgen deprivation therapy

P value

would like more informed information

Intra-operative Bleeding Pca (n=30)

-

5 (16.7%)

25 (83.3%)

BPH (n=15)

7 (46.7%)

4 (26.7%)

4 (26.7%)

P = .000

Urinary

Tayda Placeres-Hernández, Hospital Universitario de Canarias Ana Plata Bello

Incontinence Pca (n=31)

-

-

31 (100%)

BPH (n=14)

8 (57.1%)

1 (7.1%)

4 (35.7%)

P.000

Introduction & Objectives: Androgen deprivation therapy (ADT) is an essential coadjuvant therapy in some PC patients.

Although ADT has been associated with cognitive impairment its effect in the brain has not been fully investigated. Our aim is to assess the effect of ADT on cognitive performance and to analyse the brain structural features of PC patients on ADT.

Erectile Dysfunction Pca (n=31)

1 (3.2%)

4 (12.9%)

26 (83.9%)

BPH (n=14)

9 (64.3%)

1 (7.1%)

4 (28.6%)

Pca (n=31)

1 (3.2%)

5 (16.1%)

25 (80.6%)

BPH (n=14)

9 (64.3%)

2 (14.3%)

3 (21.4%)

Pca (n=31)

2 (6.5%)

5 (16.1%)

24 (77.4%)

BPH (n=14)

7 (50%)

1 (7.1%)

6 (42.9%)

Pca (n=30)

-

8 (26.7%)

22 (73.3%)

BPH (n=15)

6 (40%)

2 (13.3%)

7 (46.7%)

P=.000

Urethral Stricture

Materials & Methods: 49 PC patients with ADT were included.

Two groups were created from the median treatment time (29.47 months): <29 months and >29 months. MRI 3T study was carried out to assess patients’ cerebral features. Patients’ cognitive function was evaluated by a wide range of cognitive tests.

P =.000

Retrograde Ejaculation P=.007

Results: 24 patients were included in the group <29 months and 25 patients in the group >29 months. There were significant differences in lesional volume between groups. There was a positive correlation between the lesion volume and the period with ADT. Patients were separated according to their academic level (low education/high education), time of treatment with ADT wasn’t considered. Significant differences were found in the cognitive tests results of both groups. There are no significant differences in the grey matter volume between groups.

Further operations may be required P=.017

Conclusion: Brain lesional volume is associated with ADT increasing over time. Patients who have worse cognitive reserve (low academic level) have worse performance in cognitive assessment tests. There is no clinical-radiological correlation, showing the importance of fMRI detecting non-clinical significant early damage.

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KEYNOTE-365 Cohort I: phase 1b/2 study of pembrolizumab combined with platinum-containing chemotherapy and chemotherapy alone for treatment-emergent neuroendocrine prostate carcinoma (t-NE)

Haemoglobin and alkaline phosphatase in patients treated with docetaxel for metastatic castratesensitive prostate cancer: impact on treatment intensity and clinical outcomes Alastair Thomson, Royal Cornwall Hospital John McGrane, Maximilian Johnson, Adam Pollard

Neal Shore, Carolina Urologic Research Center Gero Kramer, Anthony Joshua, Xin Tong Li, Christian H. Poehlein, Charles Schloss, Johann de Bono, Evan Y. Yu

Introduction & Objectives: Docetaxel in metastatic castratesensitive prostate cancer (mCSPC) improves outcomes. Meta analyses have demonstrated the importance of anaemia and alkaline phosphatase (ALP) levels impacting prognosis for metastatic prostate cancer patients. We reviewed whether starting levels of haemoglobin (Hb) and ALP in patients receiving docetaxel for mCSPC affected the percentage of the planned treatment received, and whether changes in these parameters from the start compared with the end of docetaxel treatment suggested a prognostic impact.

Introduction & Objectives: Neuroendocrine prostate cancer is an aggressive disease that arises de novo or from previously treated adenocarcinoma metastatic castration-resistant prostate cancer (mCRPC). Approximately 20% of patients treated for mCRPC develop treatment-emergent neuroendocrine prostate cancer (t-NE), which shortens overall survival. Treatment for t-NE includes platinum-containing chemotherapy because of its histologic similarity to small cell lung cancer, but there is no standard of care. Pembrolizumab showed promising efficacy with acceptable safety combined with several agents for the treatment of adenocarcinoma mCRPC in other cohorts of this multicohort phase 1b/2 KEYNOTE-365 study (NCT02861573). Platinumcontaining chemotherapy alone or with pembrolizumab will be evaluated for patients with t-NE in cohort I and may provide a new treatment option for t-NE mCRPC.

Materials & Methods: The electronic prescribing database for patients receiving docetaxel for prostate cancer in our cancer centre was scrutinised. Patients were excluded if docetaxel was used in the castrate resistant setting. Levels of Hb (anaemic or not (<133g/L)) and ALP (normal or high (>130iu/L)) at the start and end of treatment were analysed. Electronic medical note review was performed to identify patient and tumour characteristics, docetaxel treatment intensity and patient outcomes. Data was collected for patients receiving docetaxel between January 2016, when NHS England recommended funding for docetaxel with initial androgen deprivation therapy (ADT) in mCSPC, and end of August 2019 with a data cut off at the end of December 2020.

Materials & Methods: Cohort I will include patients with t-NE (≥1% neuroendocrine cells in a recent biopsy specimen confirmed by central histology review). Cohort I will enroll patients with prior docetaxel treatment for mCRPC. Prior treatment with ≤2 nextgeneration hormonal agents (NHAs) for metastatic hormone sensitive prostate cancer (mHSPC) or mCRPC and 1 other chemotherapy for mCRPC is permitted. Additionally, enrollment in cohort I requires prostate cancer progression within <6 months of starting an NHA (mHSPC or mCRPC) and within <6 cycles of docetaxel for mCRPC. Each arm will enroll 40-100 patients with Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1. Eligible patients will be randomly assigned 1:1 to receive pembrolizumab 200 mg IV on day 1 of each cycle every 3 weeks (Q3W) + carboplatin AUC of 5 IV on day 1 + etoposide 100 mg/m2 IV on days 1, 2, and 3 of each 21-day cycle for 4 cycles in arm 1 or the same chemotherapy without pembrolizumab in arm 2. Pembrolizumab treatment will continue for up to 2 years until disease progression, unacceptable toxicity, or withdrawal of consent. Patients will be stratified by ECOG performance status score (0 vs 1). CT or MRI will be performed Q9W through week 54 and Q12W thereafter. Primary end points are safety and tolerability, prostate-specific antigen (PSA) response rate, and objective response rate (ORR) per RECIST v1.1 by blinded independent central review (BICR). Secondary end points include time to PSA progression; duration of response (DOR) and disease control rate (DCR) per RECIST v1.1 by BICR; ORR, DOR, DCR, and radiographic progression-free survival per Prostate Cancer Working Group 3– modified RECIST v1.1 by BICR; and overall survival. End points will be summarized for each arm without formal hypothesis testing.

Results: 188 patients receiving docetaxel for prostate cancer were reviewed, 94 patients were identified as having mCSPC. Median age was in the range 70 to 79 years old, with 21 patients (22%) having high volume disease by CHAARTED criteria (4 or more bone metastases with 1 or more outside the vertebral column or pelvis and/or visceral metastasis), 73 (78%) low volume. Median Gleason grade was 8. 66 patients (70%) received 6 cycles of docetaxel, 54 patients (57%) received at least 80% of the intended dose (6 cycles of docetaxel at 75mg/m2). Mean PSA at commencement of treatment was 538ng/ml, 89 patients (95%) had a response to the treatment with a 50% or greater reduction in their PSA level. 65 (69%) patients were alive at data cut off.

Starting level of Hb and ALP did not impact on docetaxel dose intensity, nor time to castrate resistance, nor overall survival in this patient group. Change in Hb also did not impact on duration of disease control or survival outcomes. However, a normal ALP at or below 130iu/L at the end of docetaxel, whether normal or high at the start, had improved overall survival, median 71 months if normal and 21 months if raised (p= 0.025).

Conclusion: In this patient group starting levels and changes in Hb did not help to predict treatment intensity, nor prognosis in patients treated with docetaxel for mCRPC. A raised ALP at the last dose of docetaxel demonstrated a significantly worse survival outcome. This may warrant further prospective investigation.

Results: KEYNOTE-365 is currently enrolling in Australia, Germany, New Zealand, Spain, and the United States.

Conclusion: Results from cohort I of KEYNOTE-365 will provide a preliminary estimate of the efficacy and safety of pembrolizumab combined with platinum-containing chemotherapy in t-NE mCRPC.

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Kim Van der Eecken, Ghent University Nicolette M Fonseca, Cameron Herberts, Sofie Verbeke, Sarah Win Sun Ng, Nicolaas Lumen, Elie Ritch, Andrew Murtha, Cecily Q Bernales, Elena Schönlau, Lisa Moris, Jo Van Dorpe, Matti Annala, Alexander W. Wyatt, Piet Ost

Kim Van der Eecken, Ghent University Maarten Larmuseau, Jan Vanwelkenhuyzen, Nicolaas Lumen, Kathleen Marchal, Jo Van Dorpe, Piet Ost, Bram De Laere, Sofie Verbeke

Clinical and genomic indolence in lung-recurrent metastatic hormonesensitive prostate cancer

Multifocality in prostate cancer: implications for PAM50 subtyping using an index lesion-only approach

Introduction & Objectives: PAM50 subtyping of prostate cancer harbours prognostic value and has emerged as a potential predictive biomarker. Molecular characterization of prostate cancer typically relies on a single core biopsy or resection specimen.

However it remains unclear if intra-tumour heterogeneity would impact PAM50 transcriptomic profiling, and an index lesion-only approach would be sufficient for PAM50 subtype classification. In this study, we determined to what extent foci of the same tumours are concordant or discordant with each other for PAM50 luminal and basal subtyping.

Introduction & Objectives: Pulmonary involvement without synchronous bone involvement is rare in metastatic hormonesensitive prostate cancer (mHSPC) that recurs after primary disease surgery or radiation. Guidelines recommend intensive systemic therapy, but case series suggest that patients with lungrecurrent mHSPC have relatively good outcomes. Therefore, we aimed to characterize outcomes and genomic alterations present within primary and metastatic tumours of lung-recurrent mHSPC. We hypothesized that a relatively indolent disease course would be reflected in genomic features.

Materials & Methods: We performed a retrospective cohort study in 10 mHSPC patients with metastatic lung recurrences who underwent thoracic surgery (n=9) or fine-needle biopsy (n=1) in the years after curative-intent treatment for primary disease. After histopathological review, distinct primary tumour (n=46) and metastatic lesions (n=24) were selected. From each sample, genomic features were analysed using deep multi-gene targeted sequencing and whole exome sequencing.

Materials & Methods: We performed a retrospective cohort study in patients with lymph node-positive prostate cancer (n=17) who underwent a radical prostatectomy. Histopathological evaluation of the prostate was performed upon which ≥1 index lesion plus different tumour foci (n=85, with a range of 2 to 6 samples per patient) were identified, representing distinct morphological features and histological grades. For each sample, RNA-sequencing with downstream PAM50 classification was used to classify each sample into luminal- and basal-like subtypes and investigate the extent of intra-tumour PAM50 transcriptomic heterogeneity.

Results: All patients remained alive despite a median follow-up of 139.3 months (range 97.5-170) following initial diagnosis and 55 months following lung-recurrence. Progression to metastatic hormone-resistance occurred in 2 patients. The lung-recurrent mHSPC driver landscape resembled localized prostate cancer with frequent PTEN, SPOP and chromosome 8p alterations; deleterious TP53 and DNA damage repair mutations were absent.

Despite the long median time to recurrence (76.8 months), copy numbers and clonal mutations between metastases and matched primary tumours were highly similar, suggesting intrapatient homogeneity and that archival biopsy specimens are representative of late relapses.

Results: Among the 85 primary tumour foci, the PAM50 classifier identified 3 subtypes: Luminal A (57 [67%]), Luminal B (17 [20%]), and Basal (11 [13%]) (Figure 1). Molecular subtyping revealed intratumour PAM50 subtype heterogeneity in 11/17 (65%) patients.

In 10/11 patients the Luminal A coexisted with Luminal B (n=5), Basal (n=2) or Luminal B and Basal (n=3). The Luminal B subtype coexisted with the Basal subtype in one case. In 7/9 patients with admixed Luminal B tumours, the index lesions captured the poor prognosis Luminal B subtype, which in 4 patients was only identified by profiling >1 index lesion. In two patients (ID10 and ID15) a single index lesion-only approach missed the detection of Luminal B-harbouring foci.

Conclusion: This hypothesis-generating study identified the coexistence of Luminal and Basal subtypes within the same patients’ primary high-risk prostate cancer. In the majority of cases an index lesion-only approach was sufficient to identify the poor prognosis Luminal B subtype. However, future studies on the prognostic and/or predictive value of intra-tumour PAM50 heterogeneity are warranted.

Conclusion: Our results reveal the indolent genomic etiology underlying the relatively good clinical outcomes in this and prior cohorts of lung-recurrent mHSPC. We propose that treatment of lung-recurrent mHSPC with immediate or delayed androgendeprivation therapy alone may be sufficient for long-term disease control. Prospective evaluation of lung-recurrent mHSPC as distinct from aggressive visceral disease, and inclusion in therapy de-intensification clinical trials is warranted.

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Case reports 1

2

Transforming non metastatic in metastatic prostate cancer

Our experience in the treatment of non metastatic CRPC with darolutamide

Diego Barreiro, University of Buenos Aires Federico Ferraris, Fabián Yaber

Raquel Clemente Graffigna, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife Carrion Valencia Almudena, Lorena García, Marta Jiménez Navarro, Sara González Nieto, Lara Torres León, Jonathan Rodríguez Talavera, Jesús Monllor Gisbert

Case report: A 70 year old male diagnosed with prostate cancer, Gleason 9 (4+5), DRE T2b and PSA 6,3 ng/ml. A radical prostatectomy with LND was performed on march 2017.

Pathology reports informs: pT3 N0 (0/11 nodes and extraprostatic extension).

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 metastasis-free survival, being Darolutamide the last to be approved. We present our experience with Darolutamide for the treatment of two cases of nmCRPC.

Adjuvant 3D Radiotherapy was performed (70 Gy) reaching a PSA nadir of 0,01 ng/ml in November 2017. On May 2018 the patient developed biochemical recurrence: PSA 3,4 ng/ml. Androgen deprivation therapy with LHRH agonist was started. On October 2018 PSA levels were under 0,05 ng/ml and on May 2019 PSA under 0,03 ng/ml (testosterone 0,12 ng/ml). On August 2020 PSA started to rise from 0,08 ng/ml and on November 2020 PSA reached 0,23 ng/ml (testosterone 0,10 ng/ml). PSA doubling time shorter than 10 months. On January 2020 a PSMA PET-CT was performed. PET-CT PSMA informed a single bone metastasis and one positive node.

Case report: Case 1: 79 year old male patient, with hypertension, diabetes and heart attack in 2002 as comorbidity, in treatment with ADT after progression, despite radical prostatectomy and adjuvant radiotherapy, that presented PSA increase reaching 3,6ng/dl and PSADT 2,8 months, with testosterone levels of 0,23ng/dl. Due to biochemical progression we carry out images studies, that were negative for distant disease. nmCRPC diagnosis are established and treatment with Darolutamide is approved which begins in march of 2021, maintaining the ADT therapy. After three months of treatment, a reduction in PSA is achieved, which descends to 0.34ng/dl. During the months of treatment, he has not had any adverse reaction associated to Darolutamide, preserving levels of blood pressure and blood glucose.

How do we define this patient: as a nmCSPC, a nmCRPC, a mCSPC or a mCRPC? We choose to classify the patient as a mCRPC. As first line treatment for mCPRC patient we decided to start on Enzalutamide + Denosumab.

Conclusion: In Spartan and Prosper trials the incidence of fractures reaches up to 18%, and Darolutamide is not available in Argentina. With the PET-CT PSMA we “transformed” this patient into a mCPRC one and we could treat him with a better bone protection therapy (denosumab 120 mg every 4 weeks or Zoledrinic ac 4 mg every 4 weeks).

Case 2: 68-year old male patient, without major comorbidities, who after radical radiotherapy presents disease progression. He refused surgical rescue, so started ADT therapy. Nevertheless, presented a PSA increase reaching 13ng/dl and PSADT 5 months, with testosterone levels of 0,13ng/dl. Due to biochemical progression we carry out images studies, that were negative for distant disease. nmCRPC diagnosis are established and treatment with Darolutamide is approved which begins in march of 2021, maintaining the ADT therapy. After two months of treatment, a reduction in PSA is achieved, which descends to 3,35ng/dl.

During the months of treatment, he has not had any adverse reaction associated to Darolutamide.

Conclusion: Darolutamide has been shown significantly increase metastasis-free survival and reduce the rate of PSA in patients with mCRPC at high risk of developing metastatic disease, defined as PSADT ≤10 months and PSA ≥2ng/ml. Darolutamide may be a good alternative to other new generation antiandrogens, such as Enzalutamide and Apalutamide, since in the latest studies it seems to have higher safety profile and tolerability, although there is still no evidence that directly compares the efficacy between the three drugs.

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Prostate-specific antigen 788 ng/mL: would you bet on metastatic disease?

A case report

Metastatic prostate cancer: a very rare localization Lorena García, Hospital Universitario Nuestra Señora de Candelaria Carrion Valencia Almudena, Marta Jiménez Navarro, Sara González Nieto, Lara Torres León, Raquel Clemente Graffigna, Jesús Monllor Gisbert, Jonathan Rodríguez Talavera

João de Brito Ascensão, Hospital Beatriz Ângelo Luísa Jerónimo Alves, Bruno Graça, João Pádua Marcelino

Introduction: Prostate cancer is the second most commonly diagnosed cancer in men, representing 15% of all diagnosed cancers. Diagnosis of early disease is based on a prostate biopsy that is performed due to symptoms of prostatism or an asymptomatic rise in PSA. It commonly metastasizes to regional bones and lymphatics and, more rarely, to places such as the brain, lung, skin, penis, or ureter. The ureter is rarely an organ of cancerous metastasis, regardless of the primary cancerous lesion.

Cases describing ureteral metastasis from prostate cancer are extremely rare. We present a case of ureteral metastasis from prostate cancer presenting hydronephrosis.

Introduction: Prostate cancer is the second most diagnosed carcinoma in men. Prostate-specific antigen (PSA), clinical stage and ISUP grade levels are associated with a higher likelihood of bone metastasis. Historically and arbitrarily PSA levels above 100 ng/mL have been associated with metastatic disease. However some recent observational studies reveal that for these PSA values only 45-75% of patients who underwent bone imaging had metastatic disease and even for higher values (>500 ng/mL) the rate of patients with bone metastasis varies significantly with the clinical stage and ISUP grade. We present the case of a patient with prostate cancer and an initial PSA of 788 ng/mL, cT3a and ISUP grade 4 without evidence of metastatic disease.

Case report: We present the case of a 74-year-old male patient diagnosed with prostate cancer (Gleason 4 + 5, ISUP 5, PSA 27.26 ng/ml) in 2006, treated radically with radiotherapy. In 2020, we observed a biochemical recurrence and a negative bone scan and a chest-abdomen-pelvis CT were requested, which reported a neoformative urothelial process in the left distal ureter, causing grade II hydronephrosis. In addition to the findings, the patient had a personal history of active smoker and hematuria. A left nephroureterectomy was performed with a pathological finding of acinar adenocarcinoma of the prostate that affected the wall of the left ureter. After the intervention, he begins androgen deprivation therapy. He currently has PSA levels in 0.01ng/ml.

Case report: A 55-year-old patient was referred to our department in 2014 with a PSA 788 ng/mL. He was submitted to a transrectal ultrasound-guided prostate biopsy. Histology revealed an adenocarcinoma, ISUP 4. Metastatic work-up with multiparametric prostate magnetic resonance imaging (mpMRI), bone scan and 18 F-choline positron emission computed tomography (PET/CT) revealed no further lesions. Patient started neoadjuvant complete androgen blockade and underwent retropubic radical prostatectomy. Final pathology showed a prostate adenocarcinoma, ISUP 3, with neuroendocrine tumor component and associated granulomatous prostatitis without margin or nodal involvement (0/12). Postoperative PSA level was 0.11ng/mL. On his 6th month of follow-up PSA rised to 1.11 ng/mL. Patient was re-staged with 18 F-choline PET/CT with no evidence of metastatic disease. He underwent salvage external beam radiotherapy (EBRT) reaching PSA nadir 0.6 ng/ mL. From that moment, biochemical recurrence was handled with intermittent blockade with degarelix. The patient is on his 65th month of follow-up, continent and asymtomatic, free of metastasis on conventional imaging. The latest PSA value was 4.4 ng/mL with serum testosterone 16 ng/dL.

Conclusion: Prostatic metastases in the renal and ureteral pelvis are extremely rare and may present with obstructive symptoms or as an asymptomatic mass on images, which may lead to suspicion of urothelial pathology.

Conclusion: We present a case in which a metastatic disease diagnosis was assumed and systemic treatment was started when the patient was able to undergo a local multimodal treatment from which he ended up benefiting. Seven years have passed since he was referred, and he is clinically well. The ISUP grade from the initial biopsy specimen and the presence of granulomatous prostatitis which may have contributed to a greater PSA value misled us for a greater suspicion of significant metastatic disease.

We are still far from a perfect score or biomarker to predict the presence of metastases that can obviate the use of a bone scan.

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6

The prostate: a very rare settlement of metastasis

Unusual prostate cancer presentation: haematuria and bladder involvement

Lorena García, Hospital Universitario Nuestra Señora de Candelaria Carrion Valencia Almudena, Marta Jiménez Navarro, Sara González Nieto, Lara Torres León, Raquel Clemente Graffigna, Jesús Monllor Gisbert, Nuria Orribo Morales, Jonathan Rodríguez Talavera

Sara González Nieto, Hospital Universitario Nuestra Señora de Candelaria Carrion Valencia Almudena, Adrián Amador Robayna, Lorena García García, Marta Jiménez Navarro, Lara Torres León, Raquel Clemente Graffigna, Jonathan Rodríguez Talavera, Jesús Monllor Gisbert

Introduction: Colorectal cancer is the third most commonly diagnosed type of cancer in the world and prostate cancer is the second most common cancer in men. Diagnosis of early disease is based on prostate biopsy which is carried out because of pathologic rectal examination or asymptomatic rise in PSA.

Introduction: Discerning between poorly differentiated urothelial carcinoma and high-grade prostatic adenocarcinoma is a demanding task in genitourinary pathology, particularly when the tumor includes the bladder neck, trigone and/or prostatic urethra. In clinical practice the distinction between these 2 tumors can also be challenging. Proper diagnosis is essential as they have different prognoses and clinical management.

Case report: We present the case of a 56-year-old male patient, with a medical history of rectal adenocarcinoma operated in 2015 with an abdomino-pelvic amputation and adjuvant chemotherapy and radiotherapy. The patient presented lung progression in 2016 that was treated with resection and chemotherapy. In 2020, new lung progression is detected in CT scan and the appearance of a lesion suspected of malignancy at the prostate, noted in a pelvic MRI, reported like a 16 mm nodular lesion in the prostate, highly suspicious of a neoformative process (PIRADS 5). The clinical case was presented to the urooncological committee and it was decided to perform a transperineal biopsy with a finding of adenocarcinoma of colorectal origin. The patient received radiotherapy on the pelvic lesion and in the lung progression and is currently in complete remission of the disease.

Case report: A 50-year-old male presented with haematuria, acute urinary retention, pelvic pain and right obstructive uropathy. An urethrocytoscopy was performed, but provided few details because of patient’s intolerance, thus right nephrostomy and a bladder-prostate transurethral resection (TURBT + TURP) were performed, showing a big tumour involving the prostatic urethra, trigone and bladder neck. Initial tissue analysis seemed an invasive high grade urothelial carcinoma, but once immunohistochemistry tests were performed, diagnosis changed to prostate adenocarcinoma Gleason 5+4 (ISUP grade 5). We extended the study asking for PSA test (323ng/ml) + Thorax-Abdomen-Pelvis CT-scan + Bone scan, manifesting pelvic lymph node, liver, pulmonary and bone disease. Patient received Androgen Deprivation Therapy (ADT) with Bicalutamide + Leuprolide acetate during 6 months. After 6 months his condition was re-evaluated by a multidisciplinary team, deciding to start a treatment with Docetaxel, which he is currently receiving.

Conclusion: Despite the prostate tumor being one of the most frequent in men, we should not forget the possible rare settlements of metastatic implants of other origins, as rectal.

Prostate involvement is not only due to the continuity or infiltration of the primary tumors of the prostate, being difficult to distinguish when we have a metastatic implant or a second primary.

Conclusion: Undifferentiated carcinomas involving the prostate, bladder neck and trigone require a proper diagnose from the beginning to offer the patient the best treatment.

As undifferentiated prostate carcinomas can mimic urothelial carcinoma presentation, we must not forget about this possibility, especially in young patient’s scenarios, where our promptness is fundamental.

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A case report of a rare and aggressive prostate cancer

Urinary leakage after a radical prostatectomy – a successful surgical approach

Luísa Jerónimo Alves, Hospital Beatriz Ângelo João de Brito Ascensão, Sofia Pinheiro Lopes, Rui Campos Sousa, João Pádua Marcelino

Luísa Jerónimo Alves, Hospital Beatriz Ângelo Kris Maes

Introduction: Leiomyosarcoma is an extremely rare primary malignant neoplasm of prostatic smooth muscle with less than 200 cases reported. The lack of typical symptoms often results in more advanced disease at the time of diagnosis. About one third of patients present with metastatic disease, usually in the lung or liver. Due to the rarity of this entity, approach is usually based on case reports or small retrospective series. We present a case of a of a patient with prostate leiomyosarcoma treated in our institution.

Introduction: Vesicourethral anastomotic (VUA) leakage can be a short-term complication after a radical prostatectomy with a incidence ranging from 0,3 to 15,4% considering open and minimally invasive techniques. VUA leakage can be responsible for ileus, prolonged catherization and hospital stay and increased risk of strictures. Rarely, conservative measures fail and surgical intervention is required. We present a case of a of a patient with VUA after a robotic-assisted radical prostatectomy (RARP) successfully treated with surgical intervention in our institution.

Case report: 73 year-old patient, with a previous history of benign prostatic hyperplasia (BPH) with previous negative prostatic transrectal ultrasound guided (TRUS) biopsy, presented with lower urinary retention and haematuria. On digital rectal examination, the prostate was non tender, symmetrically enlarged, without abnormalities in consistency or any palpable nodules. Serum PSA was 6,45ng/mL. Prostate multi-parametric magnetic resonance imaging reported a prostate of 100cc with pattern of “organized chaos” in the central zone, without suspicious lesions. A contrast enhanced computed tomography ruled out upper urothelial tumors as the cause of haematuria. The patient underwent transurethral resection of the prostate and histopathological examination reported a high-grade prostate leiomyosarcoma. Metastatic work-up did not revealed further lesions. After discussion in multidisciplinary meeting decision was made to proceed with radical prostatectomy. Histology of surgical specimen confirmed the diagnosis and reported seminal vesicle invasion and positive surgical margins. A multimodal approach with radiotherapy was considered although death occurred less than three months after surgery.

Case report: A 64-years-old male diagnosed with a high-risk prostate cancer underwent RARP and extended pelvic lymph node dissection. Bladder neck reconstruction was performed in a “fish-mouth” technique with a run 4-0 monocryl suture. Catheter was removed on day 7 after surgery. Immediately after bladder catheter removal, the patient presented with lower continuous abdominal and flank pain. Computed tomographic cystography revealed a right-sided VUA leakage. The attempt of a conservative approach with prolonged bladder catheterization was unsuccessful and surgical approach was decided. Intraoperatively, access to VUA was difficulted by fibrin adherences. It was confirmed the leak being caused by solely a dehiscence of the right-sided bladder neck reconstruction with the major part of the urethral reconstructing intact. The right ureteral orifice was identified and the defect was corrected with a, double layer, running 2-0 barbed suture. Subsequently, an omentum-flap was fixed over the sutured bladder defect. Bladder catheter was removed 2-weeks post-operatively with a previous cystography showing no VUA leakage. Patient turned to be continent and asymptomatic with undetectable PSA on the second month of follow-up.

Conclusion: In our patient’s case, the presence of confounding clinical features, a history of BPH and elevated PSA with a previous negative TRUS biopsy, deferred the diagnosis. After diagnostic workup excluded metastatic disease, radical surgery was promptly offered; positive surgical margins were documented, with locally advanced disease disabling the possibility of cure.

Due to the rarity of this entity, there is insufficient data regarding the clinical presentation, diagnoses and treatment approach.

Therefore, it is of the utmost importance to report its occurrence in order to improve our knowledge of its natural history.

Conclusion: Urinary leakage is a described short-term complication after a radical prostatectomy. Usually, it is managed conservatively with few cases requiring surgical correction. There is no strong evidence regarding the best timing to surgical intervention. However, after 3 weeks of catherization, it is unlikely that conservative approach will be successful. In our patient case, bladder neck reconstruction dehiscence and the proximity of ureteral orifice were, probably, responsible for failure of conservative management. Robotic approach allowed selective suturing of the bladder neck dehiscence with preservation of vesicourethral anastomosis and omentum inlay. Thus, minimizing the potential functional impact of both urinary leak and surgical intervention.

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Prostate cancer: heterogeneity disease

Somatic and germline testing in a young de novo metastatic prostate cancer patient

Marta Jiménez Navarro, University Hospital Nuestra Señora de la Candelaria Adrián Amador Robayna, Lorena García, Sara González Nieto, Lara Torres León, Raquel Clemente Graffigna, Jesus Monllor Gisbert

Celia Martín Bravo, Agencia Sanitaria Costa del Sol Casilda Llácer Pérez, Rosa M. Villatoro Roldán, Álvaro Montesa Pino, Maribel Sáez Medina, Mar Márquez, Sandra Ríos, Eva Cañada Higueras, Elena Castro

Introduction: Prostate cancer (PCa) is second most common cancer in men. In developed countries a minority of patients (47%) present advanced disease at diagnosis. The prognosis at this stages is variable and depends, among other factors, on tumor’s differentiation.

Introduction: Recently, most scientific societies have reviewed their clinical guidelines to include a recommendation for tumor and germline testing in metastatic prostate cancer (PC) patients.

It is often discussed whether tumor testing is sufficient to identify germline variants and to assess the presence of predictive biomarkers.

We present two cases of metastatic PCa at diagnosis with different treatment responses.

Case report: A 51 years old Brazilian patient diagnosed two years ago with de novo metastatic prostate cancer (T3bN0M1a) was referred to our clinic after progression to castration resistance. He had a relevant family history of cancer: father died of a brain tumor at 40 years, mother died of gastric cancer at 64 years, two maternal aunts were diagnosed with gastric cancer at 54 and 50 years, the patient’s sister presented with bilateral breast cancer at the age of 50 and his son had leukemia at the age of 3. In accordance with the updated ESMO guidelines we offered him tumor and germline testing using commercial tests. Tumor sequencing did not report any actionable variant. Germinal testing identified a pathogenic TP53 variant (c.1010G>A p.Arg337). This is a founder mutation present in 0.3% of the population from Southern Brazil frequently identified in families with Li-Frumeni Syndrome (LFS) in that region. Patients with classic LFS develop pediatric and multiple primary cancers, although a variable penetrance of TP53 variants has been observed explaining attenuated LFS phenotypes that may include PC.

Case report: Case 1: 52 year old male patient, with hypertension as comorbidity, went to emergency department with renal colic and PSA level on 4,74 ng/dl. Ultrasound found bilateral obstructive uropathy and urinary diversion with percutaneous nephrostomy was performed. Digital rectal examination showed a T3b tumor.

Prostate biopsy revealed prostate adenocarcinoma: Gleason 5+4. Computed tomography (CT) and bone scan found a pelvic mass involving prostate with visceral (liver and lung) and bone metastases. He started treatment with complete androgen deprivation. Three weeks later he died of this disease.

Case 2: 41 year old male patient, with no comorbidities, presented with spinal cord compression and PSA level on 2700 ng/dl. Prostate biopsy showed prostate adenocarcinoma: Gleason 3+4. CT and bone scan revealed no visceral disease and bone metastases involving lumbar spinal and sacrum. Treatment with complete androgen deprivation therapy was started in February 2006. Twelve years later develops castration resistant (PSA level on 347 ng/dl; previous in 152 ng/dl; nadir <0,03 ng/dl; with castrate testosterone level). At this time bone scan shows progression of sacrum bone metastases. Since then treatment with abiraterone acetate was started, and nowadays bone scan shows partial regression of sacral metastasis and no visceral disease on CT.

Our patient has been the first family member to undergo germline testing and the finding has triggered cascade testing for his relatives. It is currently unclear how this and other TP53 variants would affect the patient’s response to PC therapies.

Conclusion: Despite their low prevalence, evaluation of germline mutations in TP53 and other genes associated to cancer predisposition syndromes in PC could be relevant. Panels for germline testing should be broad and/or flexible to be adapted to the patient’s genetic background. Finally, clinicians should be aware of the limitations of somatic testing and the possibility that some germline variants are not reported.

Conclusion: Prostate cancer is an heterogeneous disease, even at similar stages at diagnosis, due to its molecular heterogeneity.

There are serum and tissue biomarkers under investigation, with promising results. Metastatic disease could benefit from precision medicine, for example, by optimization of the intensity or sequence of the treatment.

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George Naveen Weeratunga, Capital and Coast District Health Board Peter Bethwaite

Lara Torres León, Hospital Universitario Nuestra Señora de Candelaria Adrián Amador Robayna, Lorena García, Marta Jiménez Navarro, Sara González Nieto, Raquel Clemente Graffigna, Omar Halawa González, Jesús Monllor Gisbert, Jonathan Rodríguez Talavera

Mucinous prostatic urethral adenocarcinoma post external beam radiotherapy

Long time response in nonmetastatic CRPC with apalutamide: first case in our region

Introduction: Primary mucinous urethral adenocarcinoma is an extremely rare malignancy, however, is increasing recognised condition, particularly as a rare secondary malignancy post radical radiotherapy. No previous cases with prior prostatic external beam radiotherapy have been discussed in the literature. Here we describe such a case, that was managed endoscopically.

Introduction: Apalutamide is an androgen receptor inhibitor and was the first drug approved by the FDA (US Food and Drug Administration) for the treatment of non-metastatic castrationresistant Prostate Cancer (CRPCnm) in February 2018. Since the publication of the Phase III SPARTAN Study, new treatment tools/ alternatives have been introduced that modify the course of the disease improving patients' quality of life.

Case report: An 85-year-old presenting with gross haematuria for greater than one year duration was referred for cystoscopy evaluation. He had a history of ISUP grade 1 prostate adenocarcinoma which was treated with external beam radiotherapy eighteen years prior. He denied any lower urinary tract symptoms. He also was on Rivaroxaban for atrial fibrillation and previous retinal vein thrombosis. He also had recently had a colonoscopy for per rectal bleeding and iron deficiency anaemia which revealed mild radiation proctitis and no colonic lesions.

A papillary prostatic urethral lesion was identified on flexible cystoscopy. A fourteen french dense bulbar urethral stricture was also noted, the rest of the cystourethroscopy was noted to be unremarkable. At the time of cystoscopy, a transitional cell carcinoma was suspected. Histological examination revealed a lesion arising from the urethra with tubulopapillary glandular proliferation with enteric differentiation with goblet cells present.

Extension into the prostatic parenchyma with significant areas of mucinous differentiation. A diagnostic TURP was performed of the right lateral lobe of the prostate. Given the multiple comorbidities, radical surgical treatment was not offered and endoscopic surveillance with the potential for further endoscopic treatment in the event of recurrence. No recurrence was noted after 10 months of surveillance.

Case report: We present the case of a 79 year old hypertensive and dyslipidemic male diagnosed with prostate adenocarcinoma since 2003 (T3aN0M0 Gleason (3+3)) and initial PSA of 36.27 ng/ ml who received initial treatment with radical pelvic radiotherapy (72 Gy to prostate and 45 Gy to pelvis) and complete androgen blockade for 2 years. In 2008 he presented his first biochemical recurrence with PSA of 6.21 ng/ml, without bone metastases in bone scintigraphy and complete androgen blockade was established for one year, with biochemical response (PSA 0.03 ng/ ml). Intermittent ADT was established with an off period of 1 year, restarting ADT (on period of 1 year) with biochemical recurrence in 2010 with PSA of 12.20 ng/ml. During the follow-up in the off period of 1 year, a new progression was observed in 2012 with PSA of 10.77 ng/ml, confirming a new response with a PSA decreasing to 0.41 ng/ml. New biochemical recurrence in 2014 with PSA of 13.80 ng/ml. Treatment with complete androgen blockade was prescribed for 4 years with PSA progressively increasing up to 21.5 ng/ml and PSATD of 9.2 months in July 2018. It was then when it was qualified as castration resistant prostate cancer and Apalutamide was proposed as compassionate use treatment at a dose of 240 mg/day in combination with Triptorelin semiannually.

Since the beginning of the treatment, the patient presented good tolerance without side effects (ECOG 0). Imaging tests have not shown bone or organ metastatic progression, with normal liver function profile. And the analytical markers in progressive decline to 0.02 ng/ml at present.

Conclusion: Though rare, clinicians should be aware of mucinous prostate urethral adenocarcinoma should be a in the differential of patients presenting with haematuria many years post prostate radiotherapy. Exclusion of metastasis from a primary colonic mucinous adenocarcinoma part of treatment is often complicated by the co-morbidities of patients at the time of diagnosis. Endoscopy surveillance and palliative endoscopic resection is one possible treatment option as illustrated above.

Conclusion: Apalutamide has been a breakthrough in the treatment of prostate cancer in advanced stages of the disease, significantly modifying the prognosis of patients at high risk of metastasis. The use of this treatment in clinical practice has shown surprising results that augur a modification of the indications of the drug for its use in different phases of the disease; as in the high-risk metastatic debut (TITAN Study).

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Surgical salvage of prostate cancer with complete response

Basal cell prostate cancer Victor Javier Vazquez Zamora, Instituto Mexicano del Seguro Social

Lara Torres León, Hospital Universitario Nuestra Señora de Candelaria Cristina Gomez de Segura, Lorena García, Marta Jiménez Navarro, Sara González Nieto, Raquel Clemente Graffigna, Jonathan Rodríguez Talavera, Jesús Monllor Gisbert, Javier Falcón Barroso

Introduction: Prostate cancer is the second most common cause of cancer-related death in men in USA and the world.

Classical adenocarcinoma is the most common histological variant in prostate. Basal-cell carcinoma of the prostate is a rare variant of malignant tumours.

Introduction: Salvage radical prostatectomy offers the best choice of achieving local control relative to other salvage treatments despite being associated with greater postoperative complications (anastomotic stenosis, rectal injury, etc) and worse functional outcomes. European guidelines recommends it use only in experienced centres and in patients with a life expectancy of more than 10 years, pre-RSP PSA < 10 ng/mL and absence of lymph node involvement or distant metastasis.

Patient Information: 59-year-old Onset in July-2016 with difficulty in urination manifested by straining and intermittence, incomplete emptying and nocturia with initial laboratories report specific prostate antigen of 1.55 ng / ml.

Diagnostic and treatment: Due to increased symptoms, he visited urologist who performed transurethral resection with histopathological report: basal cell and adenoid cystic carcinoma of the prostate with involvement of 70% of the studied material and extensive perineural permeation, Gleason not applicable.

BCL2 +, Ki67 +, p53 +, Her2Neu negative, PS100 negative, CK20 negative and AML negative. PET CT indicated metastatic lesions in left iliac and acetabulum and liver.

Case report: We present a case of a 76-year-old male, smoker, hypertensive and COPD (chronic obstructive pulmonary disease) with diagnosis of prostate cancer (T3bN0M0; Gleason score 6 (3+3)) in September 2011 with PSA at diagnosis of 6.49 ng/mL classified as stage IIIB (AJCC prognostic group) very high risk (according to NCCN guidelines). He received initial treatment with intensity-modulated radiation therapy (IMRT) between October and December 2011 with radical intention on prostate and seminal vesicles, with a total administered dose of 75.6 Gy, and a dose per fraction of 1.8 Gy. In addition, androgen deprivation therapy (LHRH analogues) was combined for a total period of 2 years. After treatment, a nadir PSA value of 0.19 ng/mL was obtained in February 2013. In November 2020, the patient presented an elevation of PSA suspect of biochemical recurrence, although not yet meeting the criteria for biochemical recurrence (PSA 1.81 ng/mL), imaging tests were requested for further staging.

Bone scintigraphy showed no clear evidence of bone metastatic disease. Prostate MRI showed T3aN0 right prostate lesion, with increased extension in the right prostate lobe compared to the pre-treatment study. The chest-abdomen-pelvis CT scan showed a heterogeneous prostate with no signs of extraprostatic extension. With these findings, he was assessed by the Urological Tumour Committee and proposed for surgical salvage with robotic radical prostatectomy plus lymphadenectomy (June 2021) without the introduction of androgen deprivation therapy.

The anatomopathological study showed acinar and ductal adenocarcinoma Gleason 4+3 (prognostic group/grade 3) with negative lymphadenectomy and no involvement of surgical margins (pT2 pN0 R0). Two months after surgery the patient has a complete biochemical response with PSA < 0.01 ng/mL with acceptable functional outcomes.

Staged as clinical stage IV was treated with palliative chemotherapy scheme based on Paclitaxel 330mg, Carboplatin 700mg for 6 cycles of 28 days plus Zoledronic Acid 4mg. At the end of the chemotherapy treatment, IMRT 50.4Gy radiotherapy was indicated in 24Fx + boost of 24Gy in 6Fx 2 times a week.

15 months after radiotherapy treatment by PET CT report liver with multiple images compatible with metastases indicating second palliative chemotherapy scheme on Carboplatin 600mg, Gemcitabine 1.7gr on days 1 and 8 for 6 cycles and Zoledronic Acid 4mg, as well as androgen blockade with Gonadotropin Releasing Hormone (GnRH) agonist 45mg The patient was dying of liver failure 31 months after diagnosis Conclusions: In the case presented with the indicated treatment was possible to increase the months of survival after diagnosis, however, early detection is necessary to avoid deaths

Conclusion: Advances in radiotherapy techniques today, with more powerful accelerators and more precise treatment planning, have done the prostate and pelvic structures surgically approachable in patients who are candidates for radical postradiotherapy treatment. This means an increase in the therapeutic options for prostate cancer.

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We’re proud to support the Global Congress on Prostate Cancer Visit bms.com to see how we’re bringing a human touch to everything we do. © 2021 Bristol-Myers Squibb Company. All rights reserved. ONC-BE-2100114 09/21

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We are in the business of breakthroughs—our diverse, promising pipeline is focused on innovative medicines that transform patients’ lives. Our scientists are addressing some of the most challenging diseases of our time, bladder among them. We will never give up our search for more hope, for more patients, around the world.

We’re proud to support the Global Congress on Prostate Cancer

Visit bms.com to see how we’re bringing a human touch to everything we do. © 2021 Bristol-Myers Squibb Company. All rights reserved. ONC-BE-2100114 09/21

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