Les inhibiteurs de la poly-ADP ribose polymérase (iPARP) constituent une avancée majeure dans la prise en charge du cancer de la prostate résistant à la castration métastatique (CPRCm), améliorant significativement la survie, en monothérapie ou en association avec les inhibiteurs de la voie des récepteurs aux androgènes (ARPi). Cependant, des toxicités hématologiques, l’anémie, la thrombopénie et la neutropénie, peuvent compromettre la continuité du traitement, réduisant son efficacité. Les résultats des études de phase 3 et de vie réelle permettent de mieux caractériser ces toxicités. L’anémie est la plus fréquente, rapportée chez 15 à 49 % des patients à des grades≥3, survenant dans les deux premiers mois et entraînant fréquemment des interruptions (15 à 26 %) et des réductions (11 à 46 %) de dose. L’étude des mécanismes physiopathologiques impliqués dans l’apparition de ces toxicités suggère un rôle clé des protéines PARP-1 et -2 dans l’hématopoïèse. Des recommandations françaises élaborées selon une méthodologie Delphi ont permis de définir des algorithmes pratiques de prévention et de gestion de l’anémie, la neutropénie et la thrombopénie : bilan préthérapeutique, adaptation en cas d’anomalies hématologiques préexistantes et pour les populations particulières, modalités et fréquence du suivi hématologique, gestion des toxicités de grades 2 et 3. Une coordination pluridisciplinaire incluant oncologue, infirmier coordonnateur et/ou de pratique avancée et pharmacien, ainsi que l’utilisation d’outils connectés favorisant le suivi en temps réel et le partage d’informations constituent des leviers importants pour améliorer la détection précoce des toxicités et la continuité du traitement.

TPS5147 Background: Androgen deprivation therapy (ADT) plus androgen receptor pathway inhibitors (ARPIs) is the standard of care for metastatic hormone-sensitive prostate cancer (mHSPC). However, a substantial proportion of patients fail to achieve a deep prostate-specific antigen (PSA) response, which is consistently associated with worse outcomes. Deep PSA response has emerged as a robust early prognostic marker across multiple phase III trials. Patients lacking this favorable PSA decline represent a poor-risk subgroup with limited treatment personalization. Docetaxel improves survival in high-volume mHSPC and may benefit biologically aggressive disease identified by suboptimal early PSA response. REINFORCE evaluates a PSA-guided strategy of treatment intensification with docetaxel in patients without deep PSA response after apalutamide. Methods: REINFORCE is an international, multicenter, open-label, phase III randomized trial. Eligible patients are men ≥18 years with histologically confirmed mHSPC, ECOG performance status ≤1, PSA > 5 ng/ml at diagnosis of metastatic disease, ≤12 weeks of ADT before apalutamide, adequate organ function, who have received apalutamide plus ADT for 24–30 weeks, have not progressed, and have failed to achieve a deep PSA response. Deep PSA response is defined as PSA ≤ 0.2 ng/ml or PSA response ≥ 90% in combination with a PSA ≤4 ng/ml. Approximately 320 patients from 85 sites located in 6 countries will be randomized 1:1 to treatment intensification with docetaxel (75 mg/m² every 3 weeks for 6 cycles) plus continued apalutamide and ADT, or continuation of apalutamide plus ADT alone. Randomization is stratified by metastasis timing (synchronous vs metachronous), presence of visceral metastases, and PSA at study entry (≤4 vs > 4 ng/mL). The primary endpoint is event-free survival (EFS), defined as time from randomization to PSA progression, radiographic progression of soft tissue, visceral or bone lesions, according to PCWG3, or death from any cause. Secondary endpoints include time to castration resistance, radiographic and PSA progression-free survival, overall survival, safety, PSA response rates, and patient-reported outcomes. Preliminary evidence suggests that apalutamide is associated with a ≲ 10% decrease in docetaxel AUC; a dedicated pharmacokinetic sub-study will assess docetaxel drug-drug interaction and bioequivalence when co-administered with apalutamide. An independent data monitoring committee will oversee patient safety, including an early safety review after the first 18 patients included, review a pre-planned interim efficacy analysis, and evaluate pharmacokinetic data, providing recommendations to the sponsor regarding study continuation. Clinical trial information: 2025-524408-30-00.

To identify predictive biomarkers of early progression in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with [¹⁷⁷Lu]Lu-PSMA-617 radioligand therapy (RLT). This retrospective single-center study included all consecutive mCRPC patients who initiated [¹⁷⁷Lu]Lu-PSMA-617 RLT outside of clinical trials between July 2022 and May 2025, receiving at least 2 injections, and had a minimum follow-up period of 6 months. Early progression was defined as treatment discontinuation due to progression before the third injection or biochemical progression based on Prostate Cancer Working Group 3 without treatment discontinuation. Baseline clinical data, biological data, PSMA-ligand PET/CT and [18F]FDG PET/CT parameters were collected. Univariate and multivariate logistic regression were used to identify factors associated with early progression. A total of 87 patients were included. Early progression was observed in 27 (31

BACKGROUND AND OBJECTIVE:The VAPEUR randomized controlled trial compared Rezūm water vapor thermal therapy (WVTT) with combination pharmacotherapy (CP; alpha-blockers plus 5-alpha-reductase inhibitors) in sexually active men with symptomatic benign prostatic obstruction (BPO). METHODS:Overall, 151 men were randomized to WVTT (n = 75) or CP (n = 76). Primary endpoints changed from baseline to 1 yr in the International Prostate Symptom Score (IPSS) and Male Sexual Health Questionnaire (MSHQ) score. Secondary endpoints included surgical/medical treatment for recurring symptoms, ≥4 points IPSS worsening (ΔIPSS ≥4), and catheterization beyond 90 d post-procedure. KEY FINDINGS AND LIMITATIONS:At 1 yr, IPSS improvement was greater with WVTT than CP (mean difference -4.6 points; 97.5% confidence interval [CI] -7.6 to -1.6; p < 0.001), with mean improvements of 10.8 ± 6.8 versus 6.2 ± 7.7 points, respectively. MSHQ scores remained stable with WVTT (+1.1 ± 16.9) and CP (-5.2 ± 16.4). Superiority in preserving sexual function was not demonstrated with multiple imputation. Quality‑of‑life (QoL) improvement was greater with WVTT (-2.7 ± 1.8 vs -1.8 ± 2.0; p = 0.01). WVTT resulted in lower rates of surgical retreatment (1.3% vs 9.2%), ΔIPSS ≥4, (2.7% vs 13%) and post-90 d catheterization (0% vs 1.3%), but higher pharmacological retreatment (12% vs 1.3%; combined: hazard ratio = 0.52, CI 0.25-1.1, p = 0.08). Treatment‑related adverse events (AEs) were more frequent with WVTT (40% vs 28%; serious AEs, 12% vs 1.3%), largely procedure‑related; at 1 yr, 93% were resolved in WVTT versus 60% (25/42) in CP. CONCLUSIONS AND CLINICAL IMPLICATIONS:At 1 yr, WVTT provides superior symptom relief and greater QoL improvement versus CP, while preserving sexual function. These findings support WVTT as an effective alternative to CP.

Introduction L'incidence du cancer de la prostate (CaP) métastatique augmente aux États-Unis depuis 2012, alors que l'utilisation des tests PSA a diminué. Nous avons décrit l'évolution du taux d'incidence (TI) du CaP et de l’historique des tests PSA, par stade au diagnostic (localisé, avancé ou métastatique) en France. Méthodes Les CaP incidents ont été identifiés dans le SNDS sur la période 2016-2022. Le stade au diagnostic a été établi à partir du traitement initial. Les nouveaux traitements hormonaux (NTH) ont été considérés comme ciblant les CaP métastatiques. L’indication de certains NHT ayant été progressivement étendue aux CaP avancés, nous avons aussi analysé les CaP avancés ou métastatiques. L’évolution des TI et de la proportion d’hommes avec des tests PSA 2 à 5 ans avant l'incidence du CaP, par stade, ont été testées par modèles de Poisson et régressions logistiques, en ajustant sur l’âge. Résultats Sur les 359741 CaP incidents, 66,9% étaient localisés, 21,2% avancés, 7,6% métastatiques et 4,3% non classés. Le nombre de CaP incidents a augmenté entre 2016 (n=48903) et 2022 (n=55692). Le TI des CaP localisés a augmenté. Le TI des CaP avancés a diminué mais celui des CaP métastatiques a augmenté. Le TI des CaP métastatiques ou avancés a augmenté entre 2016 et 2022 chez les hommes de 50 à 74 ans (67,3 [65,6-69,0] versus 76,4 [74,6-78,1] cas pour 100000 personnes-années, p<10-3), et a diminué chez les hommes de plus de 75 ans (371,3 [363,1-379,5] versus 332,1 [324,9-339,3], p<10 3). Une proportion importante d'hommes, légèrement décroissante sur la période, avait un PSA récent avant le diagnostic de CaP (85,6 %, 78,9 % et 62,2 % pour les CaP localisés, avancés et métastatiques respectivement). Discussion/Conclusion L’évolution du TI des CaP métastatiques ou avancés dépendait de l’âge. Une forte proportion de ces patients avait bénéficié de PSA récents, mais leurs résultats sont absents du SNDS. Des études sont nécessaires pour comprendre les indications et suites données à ces tests.

363 Background: Active surveillance (AS) is standard of care for low-risk and selected intermediate risk prostate cancer (PC). However, 20 to 50% of patients (pts) will ultimately require a local treatment following AS. This study aims to assess whether apalutamide (APA) could reduce the proportion of patients requiring local treatment within 3 years. Methods: Multicentric, open label, non-comparative phase II study conducted in pts with low to intermediate risk PC randomized between APA 6 months (240 mg/d) with AS vs AS alone. The primary objective was to evaluate the proportion (π) of patients requiring a local treatment in the APA+AS arm with the aim of rejecting the null hypothesis π ≥ 30% with a 5% significance level, using an exact one-sided test for proportions. The secondary objectives were to assess pathological progression (pPFS: Gleason score or a higher % of positive cores against baseline), PSA progression (bPFS: rise in PSA levels ≥ 25%/baseline) and APA safety. Results: Between 09/2017 and 07/2021 51 pts were randomized in APA group (gp) and 40 in control (CTRL) gp. The median follow up was 36 mo (95%CI [36-37]). Median (range) age, PSA and PSA density were respectively 64 yrs (47-76), 6.8 μg/L (1.4-19.9) and 0.13 μg/L/cm³ (0.024-0.38); only 2 pts had ISUP 2 PC and 92% were d’Amico low risk group. In the APA gp, 1 did not receive APA (consent withdrawal), 4 discontinued early (<2 months) for AE and 46 received 6 mo of APA. Local treatment was performed in 37 % (90%CI, [25-50]) in APA gp and the primary objective was not achieved (p=0.88). In CTRL gp, the proportion was 44% (90% CI: [30–58]), not significantly different from APA gp (p=0.66). At 36 mo, bPFS was 55% (95% CI: [39–69]) for the APA gp vs. 42% (95% CI: [26–57]) for the CTRL gp (p= 0.07) and pPFS was 32% (95% CI: 18–46) for the APA gp vs. 11% (95% CI: [4–24]) for the CTRL gp (p= 0.01). APA toxicities (TRAEs) were observed in 98% of pts, with 14% grade 3 (G3) and 4% serious TRAEs (2% G3). Skin toxicity was observed in 30% (4%G3), 56% had asthenia/fatigue (4%G3), hypertension in 18% (4%G3), gynecomastia 62%, breast or nipple pain 36%, thyroid dysfunction 12% (2%G3), diarrhea 10%, nausea 14%, elevated transaminases in 24%. Conclusions: Apalutamide for low risk prostate cancer did not significantly reduce the proportion of patients requiring local treatment within three years. However, the results indicate improved pPFS in the APA gp. There were no new safety concerns. Clinical trial information: NCT03088124 .

Poly(ADP-ribose) polymerase inhibitors (PARPi) represent a significant advancement in the management of metastatic castration-resistant prostate cancer (mCRPC), substantially improving patient survival both as monotherapy and in combination with androgen receptor pathway inhibitors (ARPi). However, haematological toxicities, anaemia, thrombocytopenia and neutropenia, may compromise treatment continuity and thereby reduce effectiveness. Findings from phase III clinical trials and real-world studies have provided a more comprehensive understanding of these toxicities. Anaemia is the most common, occurring in 15 to 49% of patients at grade≥3, typically within the first two months of treatment. This frequently results in treatment interruptions (15-26%) and dose reductions (11-46%). Investigations into the underlying pathophysiological mechanisms suggest that PARP-1 and PARP-2 proteins play a crucial role in haematopoiesis. Based on French expert recommendations, developed using a Delphi consensus methodology, practical algorithms have been established for the prevention and management of anaemia, neutropenia and thrombocytopenia. These include pre-therapy assessment, adjustments for patients with pre-existing haematological abnormalities, consideration of specific patient populations, guidance on the frequency and modalities of haematological monitoring, and management strategies for grade 2 and 3 toxicities. Effective multidisciplinary coordination among the oncologist, coordinating and/or advanced practice nurse, and pharmacist, alongside the use of digital tools that facilitate real-time monitoring and information sharing, are key strategies to enhance early detection of toxicities and maintain continuity of treatment.

INTRODUCTION:Greenlight laser prostate photovaporization (PVP) is an alternative treatment for benign prostatic hyperplasia. However, compared to standard techniques such as transurethral resection of the prostate (TURP) and holmium laser prostate enucleation, it has certain limitations with respect to reintervention rates. The aim of our study was to identify the risk factors for reintervention due to recurrent obstruction within 12months following a photovaporization. METHODS:This retrospective, multicenter cohort study include patients treated with laser Greenlight 180W-XPS. The primary endpoint was the need for an early reintervention for obstruction. The identified causes for reintervention were: bladder neck sclerosis, urethral stricture, adenoma regrowth, managed by internal urethrotomy, PVP, or TURP. RESULTS:Data of 777 patients were analyzed and 32 reinterventions (4.1%) were recorded within 12months following surgery. Groups were comparable on preoperative data. The predictive factors for reintervention risk were: age (OR 0.92, 95% CI 0.88-0.96), laser usage time (OR 0.10, 95% CI 0.01-0.74), and energy delivered/prostate volume (OR 0.66, 95% CI 0.54-0.80). These factors were associated with a reduced risk of reintervention. The reduction is greater beyond an energy threshold of 4000J/mL (OR 0.10, 95% CI 0.04-0.27). CONCLUSION:PVP shows a low complication rate. Our results suggest that the energy delivered and the laser emission time are predictive of the quality of treatment. Despite uncertainties regarding this technique, our findings provide urologists with additional confidence in its use and offer predictive factors for assessing treatment's quality. LEVEL OF EVIDENCE: 4:

Introduction Treatment patterns for patients with bacillus Calmette-Guérin (BCG)–unresponsive high-risk non–muscle-invasive bladder cancer (NMIBC) who are ineligible for or decline radical cystectomy (RC) are inconsistently reported. We retrospectively described demographic, clinical, and treatment characteristics for these patients and assessed their clinical outcomes. Patients and Methods Medical charts of patients with BCG-unresponsive high-risk NMIBC (carcinoma in situ [cohort A] or T1/high-grade Ta [cohort B]) who were ineligible for or declined RC documented between January 1, 2011, and December 31, 2018, at 15 academic centers were reviewed. Primary objectives were to characterize demographic, clinical, and nonsurgical treatment characteristics. Secondary objectives included assessing real-world progression-free survival (rw-PFS) from muscle-invasive/metastatic disease, rw-PFS from worsening grade or stage, real-world complete response rate (rw-CRR) in cohort A, real-world event-free survival (rw-EFS) from high-risk NMIBC in cohort B, and overall survival. Results The study included 129 patients (cohort A, n = 57; cohort B, n = 72). Median age was 72.0 years (interquartile range, 64.0-80.0). Most patients were male (72.1%) and current/former smokers (69.8%). Median follow-up was 32.1 months (interquartile range, 20.7-47.6). BCG rechallenge with or without interferon-α (63.6%) was the most commonly utilized first nonsurgical therapy, followed by intravesical mitomycin C with or without electromotive drug administration or thermochemotherapy (15.5%), and intravesical valrubicin (10.9%); among those who received BCG rechallenge alone, 54.8% later received a non-BCG therapy in ≥2 subsequent treatments. 36-month rate for rw-PFS from muscle-invasive/metastatic disease was 73.5%, 66.8% for rw-PFS from worsening grade/stage, and 82.5% for overall survival. In cohort A, 6-month rw-CRR was 22.2%. In cohort B, 36-month rw-EFS rate from high-risk NMIBC was 50.2%. Conclusion After BCG-unresponsive disease, most patients with high-risk NMIBC received BCG rechallenge with or without other therapies, and >25% experienced disease progression within the first 3 years. Effective bladder-sparing options for BCG-unresponsive NMIBC are needed. Clinical trial registration N/A MicroAbstract We reviewed medical records from 15 international hospitals to understand treatment patterns and outcomes in patients with high-risk non–muscle-invasive bladder cancer (NMIBC) unresponsive to bacillus Calmette-Guérin who were ineligible for or declined radical cystectomy. We found that bladder-sparing options were historically limited and more effective bladder-sparing options are needed for this patient population.

INTRODUCTION:Androgen deprivation therapy (ADT) remains a cornerstone of treatment for both localized and metastatic prostate cancer (PC). Relugolix, an oral gonadotrophin-releasing hormone antagonist, provides a new option for achieving rapid testosterone suppression using an oral formulation. MATERIALS AND METHODS:A comprehensive literature search was conducted in PubMed by combining the search terms "relugolix", "TAK-385", "MVT-601", "prostate cancer", and "prostatic neoplasms" and focusing on prospective and retrospective studies published in English. RESULTS:The HERO pivotal phase III trial demonstrated sustained testosterone suppression in 96.7% of patients with PC treated with relugolix versus 88.8% with leuprolide through to 48weeks (P<0.001). Relugolix achieved faster testosterone suppression and recovery post-treatment and a 54% lower risk of major adverse cardiovascular events compared with leuprolide. Data from HERO and phase II studies also support its use in combination with radiotherapy or other systemic therapies. Real-world studies performed to date have confirmed the effectiveness of relugolix, with more than 98% patients achieving castrate testosterone levels. Adherence to relugolix was generally high, and its safety profile aligned with clinical trial data. Practical considerations include, among others, treatment combination and drug-drug interactions, patient choice, and oncological outcomes. CONCLUSIONS:Clinical trials and real-world evidence support relugolix as a convenient and effective ADT option for PC. It offers rapid and sustained testosterone suppression, potential cardiovascular benefits, and an alternative to injectable therapies. Long-term adherence, the use of combination treatments and related drug-drug interactions require further investigation.

This cohort study evaluates prostate-specific antigen (PSA) testing history in patients with incident prostate cancer.

Several large analyses have revealed contradictory results regarding the association between prostate cancer (PC) survival and the use of statins prescribed for prevention of dyslipidaemia or atherosclerosis complications, or of metformin prescribed for type 2 diabetes (T2D). Using data collected between 2006 and 2018 in French national health databases for 521 052 men with PC and 1 827 345 men without PC, we evaluated current evidence regarding overall survival for men with PC according to statin and/or metformin use. The highest mortality was observed in PC patients exposed to both statins and metformin (hazard ratio [HR] 2.29, 95% confidence interval [CI] 2.25-2.33). However, for patients whose first PC treatment was androgen deprivation therapy, a protective effect was observed for statin alone exposure (HR 0.91, 95% CI 0.88-0.93) and combined statin and metformin exposure (HR 0.86, 95% CI 0.85-0.87), whereas men with metformin exposure alone had higher mortality (HR 1.07, 95% CI 1.03-1.11) in comparison to non-users. This protective effect of statins was not observed for PC patients treated with radical prostatectomy. The result was confirmed using causal analysis in a Bayesian network, followed by semantic elicitation using generative artificial intelligence that compiles web-based human knowledge and dedicated literature.

Background:Haematological toxicities (anaemia, neutropenia and thrombocytopenia), a known class effect of poly-ADP ribose polymerase inhibitors (PARPi) may limit exposure to PARPi and therefore impact efficacy. Objective:This study aimed to provide practical and detailed recommendations for the prevention and management of these toxicities in metastatic prostate cancer in the real world. Design:A national consensus study was performed using a modified Delphi methodology. Methods:A multidisciplinary steering committee of 9 French experts formulated and submitted 38 statements to the vote of 33 French healthcare professionals experienced in oncology and PARPi in prostate and/or breast/ovarian cancers. Results:All recommendations achieved a consensus. Before initiating PARPi, haematological disorders should be investigated and appropriate corrective measures implemented. The haemoglobin level should ideally be ⩾10 g/dl and a minimum delay of 4 weeks should be respected after chemotherapy. Monitoring should be frequent for the first 3 months of treatment, at least every 15 days, and even more frequent in patients at high-risk of toxicity. In the event of symptomatic grade 2 or 3 anaemia, grade 2 or 3 thrombocytopenia and grade 3 neutropenia, PARPi treatment should be discontinued until return to grade 1. Transfusion may be considered in symptomatic grade 2 or 3 anaemia. Myelodysplastic syndrome/acute myeloid leukaemia should be suspected in cases of cytopenia persisting beyond 4 weeks or changes in the blood count after maintenance of an optimal therapeutic dose over the long term. Conclusion:These proposals complement existing recommendations to guide healthcare professionals in real-world practice, and so optimise metastatic prostate cancer patient's ability to maximally benefit from PARPi.

PURPOSE OF THIS DOCUMENT:The Oncology Committee of the French Urology Association (CCAFU) is proposing a 2025 summary of recommendations' changes for the management of prostate cancer (PCa). METHODS:A systematic review of the literature from July 2024 to September 2025 was conducted by the CCAFU on the evolutions of diagnostic and therapeutic management of PCa evaluating the newly published references with their level of evidence. RESULTS:Biparametric MRI is an alternative to multiparametric MRI imaging to guide biopsy decision making provided that a high-quality imaging and radiology expertise is achieved. Transperineal biopsy is the recommended approach when technically feasible. Whole-gland HIFU in patients fulfilling the HIFI trial criteria is a treatment option for intermediate-risk PCa patients. In case of metastasis-directed therapy outside the context of symptoms for oligometastatic hormone-sensitive PCa (mHSPC) disease, at least 6 months of androgen deprivation therapy (ADT) should be given. In patients with high-risk BCR treated according to the EMBARK criteria, systemic treatment with monotherapy enzalutamide may be considered. The ARPI used in addition to ADT alone can be: abiraterone, apalutamide, darolutamide, enzalutamide. In the case of HRR alterations, the combination of niraparib and abiraterone may be proposed as first-line mHSPC. In the case of a positive radiolabelled PSMA ligand PET/CT scan in a patient progressing after at least one ARPI, internal radiotherapy using [177 Lu]LuPSMA-617 may be proposed. In patients with no or mildly symptomatic bone metastatic castration-resistant PCa without visceral metastases, the combination of enzalutamide+6 cycles of radium-223 may be proposed. CONCLUSION:This 2025 summary of changes of French recommendations on PCa should help physicians to stay up-to-date with recent evolutions and aim to improve the management of PCa patients.

386 Background: After radical prostatectomy (RP), men with an undetectable PSA and specific features (extracapsular extension, seminal vesicle involvement, high Gleason score) are at risk of recurrence. No randomized prospective study has been published with LH-RH agonists in the PSA era. AFU-GETUG-20 is a phase III randomised, open, multicenter trial, designed to evaluate the benefit of adjuvant ADT with leuprorelin acetate for 24 months after radical prostatectomy in patients with high risk of recurrence. Methods: Patients with high-risk features (postoperative Gleason score > 7, or ≥ 7 with presence of high-grade Gleason patterns, or pT3b), R0, N0 or Nx, M0, and postoperative PSA < 0.1 ng/mL after RP were eligible. Patients were randomized 1:1 to leuprorelin acetate for 24 months vs observation. The primary endpoint was metastases-free survival (MFS). Secondary endpoints included overall survival, disease-specific survival, PSA recurrence-free survival, and quality of life. Originally 700 patients (350 in each arm) and 250 events were required to detect an improvement of MFS with a HR of 0.80 with a bilateral Logrank test with α= 0.05 and β= 0.20. An interim analysis was planned to test the null hypotheses at the 125th event (50% of events) but was eventually held given the low accrual rate and the accrual was stopped after 325 patients had been accrued. Results: Of 325 patients enrolled, 322 are included in the ITT population. 160 were randomized to the Leuprorelin arm and 162 to the observation arm. The median age was 64.7 years [range, 46-77 years]. The median follow-up is 96.1 months [93.6-106.1] IC95% in the leuprorelin arm and 97.2 months [91.8-101.4] IC95% in the surveillance arm. There was no statistically significant difference between arms for MFS (HR = 0.63 [0.30-1.30] 95%CI; p-= 0.204). Similar results were found for PSA relapse-free survival (HR = 0.74 [0.47-1.16]; p = 0 .187), overall survival (HR = 1.24 [0.56-2.76; p = 0.596), and specific survival (HR = 0.57 [0.10-3.17]; p = 0.512). Patients in the leuprorelin arm reported poorer HRQoD on EORTC QLQ-C30 global health scales, social function scale, and specific symptoms (fatigue, pain, dyspnoea, and insomnia). Post-hoc contrast analysis showed a difference between the groups during the treatment period. The two groups returned to comparable levels during follow-up (M36 and M48). Conclusions: Using 2 years of ADT after RP in high-risk patients with an undetectable post-operative PSA did not significantly improve MFS in AFU-GETUG-20. That the trial only accrued about half of the planned patients is the main limitation. The limited number of observed metastatic events in this population, although with a long follow-up, emphasizes the need to identify better biomarkers predicting for relapse to select candidate patients for the next generation of trials. Clinical trial information: EudraCT #:2010-022037-29 UC-0160/1003.

INTRODUCTION:Metastatic hormone-sensitive prostate cancer (mHSPC) is increasingly diagnosed due to advancements in imaging and screening. Current guidelines recommend intensified androgen deprivation therapy (ADT) as standard of care, with treatment strategies tailored according to disease burden and patient characteristics. This study aimed to explore mHSPC management practices in France through a national clinician survey and multidisciplinary consultation meeting (MCM) discussions, identifying treatment strategies and alignment with guidelines. MATERIAL AND METHODS:A two-part questionnaire, developed by a multidisciplinary scientific committee, was distributed to clinicians across France, collecting data on clinician profiles and treatment approaches, including five clinical case scenarios. Additionally, six theoretical cases were discussed in MCMs held across 10 centers to assess collaborative decision-making. RESULTS:Among 143 respondents, 53% were urologists, 22% radiation oncologists, and 25% medical oncologists, with broad regional distribution. Respondents reported managing a median of 30 mHSPC patients annually. Most adhered to national guidelines, though treatment strategies showed variability. Doublet therapy (ADT+ARPI) was widely used, while triplet therapy (ADT+ARPI+docetaxel) was more frequently considered for patients with poor prognostic disease features (e.g., high tumor volume) or younger age. In contrast, ADT alone was typically preferred for frailer patients. MCM discussions promoted greater alignment with guideline-based care. DISCUSSION/CONCLUSION:This study reveals real-world variability in mHSPC management in France, driven by clinical judgment and patient-specific factors. Multidisciplinary collaboration was critical for consistency and personalized care. Ongoing efforts should focus on addressing practice variability, incorporating patient preferences, and integrating emerging therapies to improve outcomes while minimizing loss of therapeutic opportunity. LEVEL OF EVIDENCE:(HAS): 4 (descriptive studies, surveys, expert opinions).

STUDY QUESTION:What is the direct effect of mumps virus (MuV) replication within the human testis on the tissue innate immune responses and testicular cell functions? SUMMARY ANSWER:MuV induces an early pro-inflammatory response in the human testis ex vivo and infects both Leydig cells and Sertoli cells, which drastically alters testosterone and inhibin B production. WHAT IS KNOWN ALREADY:Despite widespread vaccination efforts, orchitis remains a significant complication of MuV infection, especially in young men, which potentially results in infertility in up to 87% of patients with bilateral orchitis. Our understanding of MuV pathogenesis in the human testis has been limited by the lack of relevant animal models, impairing the development of effective treatments. STUDY DESIGN, SIZE, DURATION:Normal testes were collected from seven uninfected post-mortem donors (median age of 55 years, range 29-79). Organotypic cultures of human testis explants exposed or not to MuV ex vivo were undertaken for 10 days. Utilizing this original ex vivo model, we investigated the replication kinetics of MuV, identified its target cells, characterized the innate immune responses of the testis to the virus, and assessed the impact of the infection on testicular cell functions. PARTICIPANTS/MATERIALS, SETTING, METHODS:Human testis explants were exposed overnight to MuV at a multiplicity of infection of 1 and cultured on polyethylene terephthalate inserts at the air/medium interface for 10 days. MuV replication in human testis explants was evidenced by measuring the release of infectious viral particles in plaque-forming assay and viral RNA in RT-qPCR, as well as by in situ detection of replicative viral RNA in testicular cells all along the 10-day culture period. Infected cells were characterized by microscopy using specific cell markers and a probe against viral RNA. The innate immune response was assessed using RT-qPCR, in situ hybridization, and LegendPlex. Testosterone and its precursors were measured in the supernatants of MuV and mock-infected explants by mass spectrometry, while inhibin B was measured by ELISA. The impact of MuV infection on testis tissue and cells was further explored by lactate dehydrogenase viability assay, RT-qPCR, immunohistochemistry, and western blot. MAIN RESULTS AND THE ROLE OF CHANCE:MuV robustly replicated in human testicular explants all along the 10-day culture, progressing from the interstitial tissue, where it infected Leydig cells, macrophages, and peritubular cells, to the seminiferous tubules, where it targeted Sertoli cells. Unlike Zika virus, another testis-tropic virus, MuV triggered a pro-inflammatory response within 4 h in exposed human testis explants, characterized by transcriptional upregulation of interleukin 1 beta (IL1B) in sentinel cells. This was followed by the tissue release of inflammatory mediators (P = 0.02 for IL1B at 72 h and Day 7) and the dynamic regulation of interleukin 10 (IL10) upon viral replication. MuV replication inhibited testosterone production from Day 7 onwards (P < 0.03) by disrupting the steroidogenic activity of Leydig cells at the level of cytochrome P450 family 17 subfamily A member 1 (CYP17A1) and decreased inhibin B secretion from Sertoli cells from Day 4 onwards (P < 0.03), which exhibited features of pyroptosis. LARGE SCALE DATA:N/A. LIMITATIONS, REASONS FOR CAUTION:This ex vivo study, which demonstrates the direct impact of MuV replication in the human testis, does not assess the additional role of infiltrating peripheral immune cells in testicular lesions. WIDER IMPLICATIONS OF THE FINDINGS:These findings demonstrate that MuV infection of the human testis elicits a distinct early innate immune response in contrast to Zika virus, known for its silent persistence. This difference offers a potential explanation for the development of MuV-induced testis inflammation. Furthermore, our study provides evidence that MuV directly disrupts crucial testicular functions in the absence of leukocytic infiltrates. These data advance our understanding of the early events of MuV pathogenesis in the testis and provide a basis for further investigation into the mechanisms of orchitis versus silent infection. The ex vivo model of MuV-infected human testis developed in this study will serve as a valuable tool for evaluating antiviral strategies aimed at preserving testicular function in MuV-infected men. STUDY FUNDING/COMPETING INTEREST(S):This study was supported by grants from the French National Research Agency (grant number ANR-21-CE15-0021-01) and from the Fondation pour la Recherche Médicale (FRM EQU202203014611), as well as by Institut National de la Santé et de la Recherche Médicale and the University of Rennes. The authors have no competing interests. TRIAL REGISTRATION NUMBER:N/A.

BACKGROUND:Since prostate cancer (PCa) risk is associated with ethnicity, it is crucial to investigate ethno-geographic variations in PCa studies. Periprostatic adipose tissue (PPAT) has been involved in cancer aggressiveness through the release of lipids and inflammatory mediators, and we previously reported a different lipid composition of PPAT according to the ethno-geographic origin. We aimed to analyze the expression of a panel of adipokines in PPAT from African-Caribbean and Caucasian patients, in correlation with features of PCa aggressiveness and lipid composition. METHODS:Adipokines expression was analyzed by RTqPCR in PPAT from 110 Caucasians and 50 African-Caribbeans patients, in parallel with the characterization of fatty acids and cholesterol content. RESULTS:The most expressed cytokines were IL10, leptin and IL8. The expression of most adipokines was higher in PPAT from Caucasians compared to African-Caribbean patients. IL6 was associated with features of PCa aggressiveness in Caucasians, with a difference close to significance. Most cytokines were associated with the lipid composition of PPAT, mainly with arachidonic acid and free cholesterol content. CONCLUSIONS:The differential cytokines expression in PPAT from African-Caribbean patients compared to Caucasians probably reflects a different inflammatory status. The close relationship between adipokines expression and lipid composition highlights the importance of diet and lipid metabolism in adipose tissue inflammation.