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Les traitements médicaux de l’hyperplasie bénigne et du cancer de la prostate reposent essentiellement sur l’inhibition de la signalisation androgénique. Bien qu’initialement efficaces, ces traitements sont tôt ou tard confrontés à une résistance thérapeutique. Des données récentes de séquençage d’ARN sur cellules uniques montrent que les cellules luminales survivant à la déprivation androgénique dans ces contextes pathologiques présentent un profil moléculaire semblable à celui de cellules luminales progénitrices, présentes en faible quantité dans un contexte physiologique. Ce profil moléculaire pourrait constituer un hub de résistance à la castration et résulter, en partie, de la reprogrammation des cellules luminales tumorales. L’inhibition thérapeutique de cette plasticité cellulaire constitue une piste prometteuse pour limiter la progression du cancer prostatique.

Increasing use of multiparametric magnetic resonance imaging (mpMRI) has come with heterogeneity in image quality. The Prostate Imaging Quality (PI-QUAL) score is under scrutiny to assess its usefulness in predicting clinical outcomes.To compare upstaging of localized disease on mpMRI (mrT2) to locally invasive disease in radical prostatectomy (RP) specimens (≥pT3a) in relation to PI-QUAL.Patients treated with RP between 2015 and 2020 who underwent 1.5-3-T mpMRI within 6 mo before surgery and had systematic and mpMRI-US targeted biopsies were included. mpMRI scans were retrospectively assigned a PI-QUAL score, and prospectively acquired Prostate Imaging-Recording and Data System (PI-RADS) scores (version 2.0 or 2.1) were used. PI-QUAL scores were categorized as nondiagnostic (PI-QUAL3), sufficient (PI-QUAL 3), or optimal (PI-QUAL3).We assessed the relationship between the PI-QUAL score and upstaging using multivariate logistic regression. mpMRI, clinical, and pathological findings were compared using χWe identified 351 patients, of whom 40 (11.4%) had PI-QUAL3, 57 (16.3%) had PI-QUAL 3, and 254 (72.3%) had PI-QUAL3 scores. The distribution of PI-QUAL3 (0-33.6%;In comparison to PI-QUAL ≥3, PI-QUAL3 was significantly associated with a higher rate of upstaging from organ-confined disease on mpMRI to locally advanced disease on pathology, lower detection rates for PI-RADS 5 lesions and extraprostatic extension, and a lower number of suspicious lesions.Poor image quality for magnetic resonance imaging (MRI) scans of the prostate is associated with underestimation of the stage of prostate cancer.

ImportanceRecently, several large, high-quality analyses have shown opposing results regarding the association between 5α-reductase inhibitor (5-ARI) use and prostate cancer (PCa) mortality.ObjectiveTo systematically evaluate the current evidence regarding 5-ARI use and PCa mortality.Data SourcesA literature search began in and was conducted through August 2022 using PubMed/Medline, Embase, and Web of Science databases.Study SelectionStudies were deemed eligible if they included male patients of any age who were 5-ARI users and were compared with those who were nonusers if they analyzed PCa mortality in randomized clinical trials and prospective or retrospective cohort studies.Data Extraction and SynthesisThis study was reported in accordance with Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. Adjusted hazard ratios (HRs) were extracted from published articles. Data analysis was performed in August 2022.Main Outcomes and MeasuresThe primary outcome was PCa mortality among 5-ARI users vs nonusers. The inverse variance method with adjusted HRs and random-effect models were used to determine the association between 5-ARI use and PCa mortality. Two subgroup analyses were performed to assess the effect of 2 main confounders: prostate-specific antigen level and PCa diagnosis at baseline.ResultsAmong 1200 unique records screened, 11 studies met the inclusion criteria. A total of 3 243 575 patients were included: 138 477 users of 5-ARI and 3 105 098 nonusers. There was no statistically significant association between 5-ARI use and PCa mortality (adjusted HR, 1.04; 95% CI, 0.80-1.35; P = .79). No significant association was found when the analysis was restricted to studies that excluded patients with a diagnosis of PCa at baseline (adjusted HR, 1.00; 95% CI, 0.60-1.67; P = .99) or the analysis was restricted to prostate-specific antigen–adjusted studies (adjusted HR, 0.76; 95% CI, 0.57-1.03; P = .08).Conclusions and RelevanceThis systematic review and meta-analysis, which draws on 2 decades of epidemiologic literature and includes more than 3 million patients, found no statistically significant association between 5-ARI use and PCa mortality but provides important data to inform clinical care.

Figure S1 : Heterogeneous distribution of various subpopulations of intratumor CD8+T cells defined by the differential expression of PD1 and Tim-3 using an in situ multiparametric immunofluorescence technique. Figure S2: PD-1 and Tim-3 co-expression on CD8+T cells (in situ IF analyzis) correlates with clinical parameters of RCC aggressiveness Figure S3 : Relationships between the total number of intratumor T cells and subpopulations of CD8+T cells and Progression Free Survival Figure S4: Heterogeneous distribution of various subpopulations of tumor-infiltrating CD8+T cells defined by the differential expression of PD1 and Tim-3 analyzed by cytometry Figure S5: Patients who co-expressed PD-1 and Tim-3 on CD8+T cells more often exhibited clear cell RCC histology Figure S6: Tim-3 expression was decreased on PD-1+CD8+T cells after treatment with collagenase Figure S7 : PD-1 and Tim-3 expression on renal cell carcinoma by in situ immunofluorescence analysis Figure S8 : Blockade experiments with anti-PD-1 and anti-Tim-3 on bulk TIL

Inhibitory receptors expressed by T cells mediate tolerance to tumor antigens, with coexpression of these receptors exacerbating this dysfunctional state. Using the VectraR automated multiparametric immunofluorescence technique, we quantified intratumoral CD8+ T cells coexpressing the inhibitory receptors PD-1 and Tim-3 from patients with renal cell carcinoma (RCC). A second validation cohort measured the same parameters by cytometry. The percentage of tumor-infiltrating CD8+ T cells coexpressing PD-1 and Tim-3 correlated with an aggressive phenotype and a larger tumor size at diagnosis. Coexpression of PD-1 and Tim-3 above the median conferred a higher risk of relapse and a poorer 36-month overall survival. Notably, other CD8+T-cell subsets did not exert a similar effect on overall survival. Moreover, only the PD-1+Tim-3+ subset of CD8+ T cells exhibited impaired function after stimulation. Our findings establish intratumoral Tim-3+PD1+CD8+ T cells as critical mediators of an aggressive phenotype in RCC. Use of the Vectra tool may be useful to identify similarly critical prognostic and predictive biomarkers in other tumor types and their response to immunotherapy. Cancer Res; 77(5); 1075–82. ©2016 AACR.

Table S1: Baseline clinical characteristics of the 87 primary clear cell RCC patient selected for multiparametric immunofluorescence in situ analysis Table S2: Baseline clinical characteristics of the 42 primary RCC patient with analysis of fresh tumor TIL Table S3 : List of antibodies used for cytometry and in situ immunofluorescence Table S4: Correlation between the total number (Nb) of CD8+T cells and those expressing Tim-3 and/or PD-1 and the Fuhrman grade and UISS. Table S5 : RCC patients characteristics in the prospective cohorts Table S6 : RCC patients characteristics in the retrospective cohorts

Introduction: The aim of the study was to report the 30-day mortality (30DM) after renal trauma and identify the risk factors associated with death. Methods: The TRAUMAFUF project was a retrospective multi-institutional study including all patients with renal trauma admitted to 17 French hospitals between 2005 and 2015. The included population focused on patients of all age groups who underwent renal trauma during the study period. The primary outcome was death within 30 days following trauma. The multivariate logistic regression model with a stepwise backward elimination was used to identify predictive factors of 30DM. Results: Data on 1,799 renal trauma were recorded over the 10-year period. There were 59 deaths within 30 days of renal trauma, conferring a 30DM rate of 3.27%. Renal trauma was directly involved in 5 deaths (8.5% of all deaths, 0.3% of all renal trauma). Multivariate stepwise logistic regression analysis revealed that age >40 years (odds ratio [OR] 2.18; 95% confidence interval [CI]: 1.20–3.99; p = 0.01), hemodynamic instability (OR 4.67; 95% CI: 2.49–9; p < 0.001), anemia (OR 3.89; 95% CI: 1.94–8.37; p < 0.001), bilateral renal trauma (OR 6.77; 95% CI: 2.83–15.61; p < 0.001), arterial contrast extravasation (OR 2.09; 95% CI: 1.09–3.96; p = 0.02), and concomitant visceral and bone injuries (OR 6.57; 95% CI: 2.41–23.14; p < 0.001) were independent predictors of 30DM. Conclusion: Our large multi-institutional study supports that the 30DM of 3.27% after renal trauma is due to the high degree of associated injuries and was rarely a consequence of renal trauma alone. Age >40 years, hemodynamic instability, anemia, bilateral renal trauma, arterial contrast extravasation, and concomitant visceral and bone lesions were predictors of death. These results can help clinicians to identify high-risk patients.

BACKGROUND Active surveillance (AS) is a validated option for the treatment of small renal masses (SMRs), especially in older patients. This study investigates the oncologic outcomes and competitive mortality of older patients prospectively assigned to AS. METHODS We conducted a monocentric study on patients ≥75 years treated between 2011 and 2016 for a SMR. Treatment modalities, biopsy data, survivals (overall, specific, cancer progression) and delayed interventions (DI) were analyzed. RESULTS Overall, 106 patients (median age 80.5 years) were included, of which 41 were managed by AS during a follow-up of 3.4 years [0-7.1]. Seven patients (17%) had a primary biopsy with 3 confirmed renal cell carcinomas. Fourteen patients (34.1%) presented with progression (29.2% local; 4.9% metastatic), 8 (19.5%) requiring DI (75% ablative therapy and 25% radical nephrectomy). Overall survival (OS) was 68.3% and cancer specific survival (CSS) was 95.1% during the study period. Competitive mortality was higher (84.6%) than cancer specific mortality (15.4%), p=0.001. CONCLUSION The growth rate of progression including 4.9% metastatic progression underlines the value of AS compared to simple watchful surveillance in the treatment of SMRs in older patients. Of note, the higher competitive mortality confirm that AS should be preferred to active intervention at the beginning of the management. MICROABSTRACT Management of small renal tumors in older patients is challenging. This study shows that older patients managed by active surveillance (AS) will mostly die from other causes than renal cancer, confirming the safety of AS. However, the significant progression rate under AS confirms the need of a careful and vigilant radiological follow-up rather than a simple watchful waiting surveillance.

Background: High-fidelity repair of DNA damage repair (DDR) (either single-strand- [SSBs] or double-strand breaks [DSBs]) is necessary for maintaining genomic integrity and cell survival. DDR alterations are commonly found in genitourinary malignancies involving either DSB repair by the homologous recombination (HR) repair (HRR) system (BRCA1/2 pathway) or the SSB repair through the poly (ADP-ribose) polymerase (PARP) pathway. PARP inhibitors (PARPi) exploit defects in the DNA repair pathway through synthetic lethality, DSBs being repaired only in HR-proficient cells but not in HR-deficient (HRD) cells. Summary: A growing body of evidence supports the need for identification of germinal and somatic DDR alterations in patients with genitourinary malignancies. PARPi have already shown significant survival benefits in patients harboring HRR mutations in advanced settings, paving the way for precision medicine. Key Messages: In advanced prostate cancer (PCa), somatic mutations in HRR pathway are observed in up to 27% of metastatic resistant-to-castration PCa (mCRPC), although occurring early in PCa development, and mainly involving BRCA2, ATM, CHEK2, and BRCA1. Overall, germinal alterations are present in roughly 30–50% of cases of HRR alterations, and relative risk of PCa in germinal BRCA2 alteration carriers is 4.65-fold higher compared to noncarriers. Determination of DDR gene status is recommended in metastatic patients, a fortiori in mCRPC setting, since it could be a putative biomarker of response to first line of treatment (androgen-receptor signaling inhibitors [ARSI] vs. taxane-based chemotherapy) and allows to assess eligibility for PARPi use. Thus, olaparib (combined with androgen deprivation therapy) recently improved overall survival in mCRPC HRD patients, after new hormonal therapy (NHT) and led to its approvement for patients with an alteration in 14 of 15 prespecified HRR genes. Moreover, since preclinical data suggested synergic action between PARPi and ARSI, the use of either olaparib or niraparib has also been proposed in combination with NHT, with a radiological progression-free survival improvement when used with abiraterone. In urothelial carcinoma, a DDR gene alteration is identified in 23–54% of patients mostly in muscle-invasive bladder cancer, with a strong association between DDR gene mutation and a higher tumor mutation burden and sensitivity to cisplatin-based chemotherapy and immunotherapy. Recent phase 2 trials supported the use of HRR status to select patients for PARPi treatment in advanced urothelial carcinoma. Finally, in renal cell carcinomas (RCCs), pathogenic germline variants in DDR genes were identified in 7.3% of the cases, and deleterious somatic alterations have also been described as recurrent genomic events in patients with advanced RCC.

International audience; Objective Annual countrywide data are scarce when comparing surgical approaches in terms of hospital stay outcomes and costs for radical prostatectomy (RP). We aimed to assess the impact of surgical approach on post-operative outcomes and costs after RP by comparing open (ORP), laparoscopic (LRP), and robot-assisted (RARP) RP in the French healthcare system. Patients and methods Data from all patients undergoing RP in France in 2020 were extracted from the central database of the national healthcare system. Primary endpoints were length of hospital stay (LOS including intensive care unit (ICU) stay if present), complications (estimated by severity index), hospital readmission rates (at 30 and 90 days), and direct costs of initial stay. Results and limitations A total of 19,018 RPs were performed consisting in ORP in 21.1%, LRP in 27.6%, and RARP in 51.3% of cases. RARP was associated with higher center volume (p < 0.001), lower complication rates (p < 0.001), shorter LOS (p < 0.001), and lower readmission rates (p = 0.004). RARP was associated with reduced direct stay costs (2286 euros) compared with ORP (4298 euros) and LRP (3101 euros). The main cost driver was length of stay. The main limitations were the lack of mid-term data, readmission details, and cost variations due to surgery system. Conclusions This nationwide analysis demonstrates the benefits of RARP in terms of post-operative short-term outcomes. Higher costs related to the robotic system appear to be balanced by patient care improvements and reduced direct costs due to shorter LOS.

International audience; PURPOSE: To review current evidence regarding the management of de novo, oligometastatic, castration-sensitive prostate cancer (PCa). METHODS: A literature search was conducted on PubMed/Medline and a narrative synthesis of the evidence was performed in August 2022. RESULTS: Oligometastatic disease is an intermediate state between localized and aggressive metastatic PCa defined by ≤ 3-5 metastatic lesions, although this definition remains controversial. Conventional imaging has limited accuracy in detecting metastatic lesions, and the implementation of molecular imaging could pave the way for a more personalized treatment strategy. However, oncological data supporting this strategy are needed. Radiotherapy to the primary tumor should be considered standard treatment for oligometastatic PCa (omPCa). However, it remains to be seen whether local therapy still has an additional survival benefit in patients with de novo omPCa when treated with the most modern systemic therapy combinations. There is insufficient evidence to recommend cytoreductive radical prostatectomy as local therapy; or stereotactic body radiotherapy as metastasis-directed therapy in patients with omPCa. Current data support the use of intensified systemic therapy with androgen deprivation therapy (ADT) and next-generation hormone therapies (NHT) for patients with de novo omPCa. Docetaxel has not demonstrated benefit in low volume disease. There are insufficient data to support the use of triple therapy (i.e., ADT + NHT + Docetaxel) in low volume disease. CONCLUSION: The present review discusses current data in de novo, omPCa regarding its definition, the increasing role of molecular imaging, the place of local and metastasis-directed therapies, and the intensification of systemic therapies.

Summary Objectif Evaluate kidney autotransplantation (KAT) and ileal ureter substitution (IUS) practice and outcome as alternatives to indwelling ureteral stents for the management of long ureteral stenosis (US). Material We included all patients treated for US with KAT or IUS in 5 French university urology centers between 2010 and 2018. We excluded US due to urothelial carcinoma. Primary endpoint was the preservation of ipsilateral kidney and renal function without any urinary diversion. Results 22 patients were treated with KAT (n = 8, 36.4%) and IUS (n = 14, 63.6%). Mean US length was 4.6 cm and 6 cm (P = 0.52) in KAT and IUS groups respectively. US etiologies were lithiasis, iatrogenic, retroperitoneal fibrosis or extrinsic compression. US level was varied. The surgery was described as difficult because of peritoneal adhesions or major peri-ureteral fibrosis. Mean operating time and hospital stay were 336 and 346 minutes (P = 0.87) and 8 and 15 days respectively (P = 0.001). Postoperative complications were mostly Clavien ≤ 2 (n = 17, 77.3%). Revision surgery was required in the KAT group in 3 cases (37.5%), for textiles, renal vein thrombosis and anastomotic leak, none in the IUS group. The mean follow-up was 15.7 months. All but one (in the KAT group) ipsilateral kidneys were preserved, without renal function impairment (Δcreat +2.1 vs. +2.4 μmol/l respectively, P = 0.67), nor urinary diversion. Conclusion KAT and IUS are safe alternatives whose indication depends on surgeons expertise. Our study pointed out the scarcity of this practice suggesting the need to refer patients to expert centers. Level of evidence 3.

Objectives: The aim of this study was to assess the natural history of prostate cancer (PCa) in renal transplant recipients (RTRs) and to clarify the controversy over whether RTRs have a higher risk of PCa and poorer outcomes than non-RTRs, due to factors such as immunosuppression. Patients and Methods: We performed a retrospective multicenter study of RTRs diagnosed with cM0 PCa between 2001 and 2019. Primary outcomes were overall (OS) and cancer-specific survival (CSS). Secondary outcomes included biochemical recurrence and/or progression after active surveillance (AS) and evaluation of variables possibly influencing PCa aggressiveness and outcomes. Management modalities included surgery, radiation, cryotherapy, HIFU, AS, and watchful waiting. Results: We included 166 men from nine institutions. Median age and eGFR at diagnosis were 67 (IQR 60–73) and 45.9 mL/min (IQR 31.5–63.4). ASA score was >2 in 58.4% of cases. Median time from transplant to PCa diagnosis was 117 months (IQR 48–191.5), and median PSA at diagnosis was 6.5 ng/mL (IQR 5.02–10). The biopsy Gleason score was ≥8 in 12.8%; 11.6% and 6.1% patients had suspicion of ≥cT3 > cT2 and cN+ disease. The most frequent management method was radical prostatectomy (65.6%), followed by radiation therapy (16.9%) and AS (10.2%). At a median follow-up of 60.5 months (IQR 31–106) 22.9% of men (n = 38) died, with only n = 4 (2.4%) deaths due to PCa. Local and systemic progression rates were 4.2% and 3.0%. On univariable analysis, no major influence of immunosuppression type was noted, with the exception of a protective effect of antiproliferative agents (HR 0.39, 95% CI 0.16–0.97, p = 0.04) associated with a decreased risk of biochemical recurrence (BCR) or progression after AS. Conclusion: PCa diagnosed in RTRs is mainly of low to intermediate risk and organ-confined at diagnosis, with good cancer control and low PCa death at intermediate follow-up. RTRs have a non-negligible risk of death from causes other than PCa. Aggressive upfront management of the majority of RTRs with PCa may, therefore, be avoided.

BHD syndrome is characterized by an increased risk of bilateral and multifocal renal cell carcinoma (RCCs), but is rarely metastatic. Our report aims to analyze the outcome of patients with BHD syndrome who underwent percutaneous thermal ablation (TA). The present report included six BHD syndrome patients (five men) with a mean age of 66 ± 11 (SD) years who had a proven germline FLCN gene mutation and underwent TA for a renal tumor. Nineteen renal tumors (median two tumors per patient; range: 1–3), including seven chromophobe RCCs, five clear-cell RCCs, four papillary RCCs, two clear-cell papillary RCC, and one hybrid oncocytic/chromophobe tumor were treated in 14 ablation sessions. The mean size of the tumors was 21 ± 11 (SD) mm (median: 20 mm; interquartile range (IQR): 14–25 mm) for a mean volume of 7 ± 11 (SD) mL (median: 3; IQR: 1–5 mL). Technical success was achieved in all ablation sessions (primary success rate, 100%). The procedure was well tolerated under conscious sedation with no significant Clavien–Dindo complication (grade 2, 3, 4). All patients were alive with no distant metastasis during a median follow-up period of 74 months (range: 33–83 months). No local tumor progression was observed. The mean decrease in estimated glomerular filtration rate was 8 mL/min/1.73 m2. No patients required dialysis or renal transplantation. In this case series, percutaneous TA appeared as a safe and efficient nephron-sparing treatment for treating RCCs associated with BHD syndrome, even in the case of advanced chronic kidney disease.

To externally validate the STAR-CAP prognostic system for prostate cancer (PCa) and compare it to the CAPRA score to predict for biochemical recurrence (BCR) after radiation therapy (RTx). We included patients treated with RTx between 2002 and 2021 for non-metastatic PCa at our institution. BCR was defined based on Phoenix criteria. The 5-year BCR-free survival was assessed by univariable Kaplan–Meier analyses and log-rank test. Multivariable Cox regression models tested the independent association of each model for BCR. Performance of both models to predict 5-year BCR-free survival was assessed using the area under the curve (AUC). The 2768 patients included were treated with high dose rate brachytherapy (13.3%) as a boost to external beam radiation therapy (EBRT), low dose rate seed brachytherapy (50.4%) or EBRT alone (35.9%). 14.4% of patients received concomitant androgen deprivation therapy (ADT). 222 patients experienced BCR (8%), with a median follow-up of 56 months. The 5-year BCR-free survival ranged from 88 (high risk) to 96% (low risk) in the STAR-CAP classification, and from 87 (high risk) to 97% (low risk) in the CAPRA system (p

Summary Introduction Neoadjuvant chemotherapy (NAC) is now recommended to treat muscle-invasive bladder cancer (MIBC) but is not always executed in real life. This study aims to evaluate the proportion of patients with MIBC who receive an optimal NAC, and to present the predictive factors of its achievement. Methods This monocenter retrospective study included all the patients who underwent radical cystectomy for ≥ pT2NxM0 MIBC between 2013, January and 2018, December. NAC consisted in 4–6 cycles of MVAC (methotrexate, vinblastine, adriamycin, and cisplatin) or 4 cycles of GC (gemcitabin, and carboplatin). Demographic (sex, age, ECOG-PS, glomerular filtration rate [GFR], and cN stage), surgical (urinary derivation, time of surgery, blood loss, and complications), and oncological characteristics were analyzed. Multivariate analysis are made to find predictors of administration of NAC. Results One hundred and twenty-seven patients were included. Thirty received CNA (24%). Patients who underwent CNA were younger, with better ECOG and better GFR. Multivariate analysis showed that cN+ stage and better GFR were significantly associated to administration of NAC. Eight patients (27%) couldn’t receive an optimal treatment due to toxicity. Perioperative complication rates were similar, with or without NAC. Patients who underwent NAC had a worse GFR after treatment (−17 versus +5 mL/min, P Conclusion Due to the risks of toxicity, NAC can only be proposed to selected population, which is not the current patients. Immunotherapy could allow to treat more patients because of better tolerance. Level of evidence 3.

Recently, Eggener et al. reignited a debate consisting to redefine Gleason Grade Group (GGG) 1 prostate cancer (PCa) as a precancerous lesion to reduce overdiagnosis and overtreatment. However, historical cohorts showed that some GGG1-labeled disease at biopsy may be underestimated by the standard PCa diagnostic workup. The aim was to assess whether the risk of adverse features at radical prostatectomy (RP) in selected GGG1 patients still exists in the era of pre-biopsy mpMRI and image-guided biopsies.We retrospectively reviewed our data from a European RP dataset to assess in contemporary patients with GGG1 at mpMRI-targeted biopsy the rate of adverse features at final pathology, defined as ≥ pT3a and/or pN+ and/or GGG ≥ 3.A total of 419 patients with cT1-T2 cN0 GGG1-PCa were included. At final pathology, 143 (34.1%) patients had adverse features. In multivariate analysis, only unfavorable intermediate-risk/high-risk disease (defined on PSA or stage) was predictive of adverse features (OR 2.45, 95% CI 1.11-5.39, p = 0.02). A significant difference was observed in the 3-year biochemical recurrence-free survival between patients with and without adverse features (93.4 vs 87.8%, p = 0.026). In sensitivity analysis restricted low- and favorable intermediate-risk PCa, 122/383 patients (31.8%) had adverse features and no preoperative factors were statistically associated with this risk.In this European study, we showed that there is still a risk of underestimating GGG1 disease at biopsy despite the routine use of image-guided biopsies. Future studies are warranted to improve the detection of aggressive disease in GGG1-labeled patients by incorporating the latest tools such as genomic testing or radiomics.

The risk of acute renal failure (ARF) following iodinated contrast media injection has long been overestimated because of the previous use of more toxic ICPs and uncontrolled studies. Nowadays, this concept is being questioned. Patients with severe renal failure and/or ARF are the only group still considered at risk. In these patients, it is necessary to discuss an alternative without an iodinated contrast agent. Contrast-enhanced ultrasound, MRI, spectral CT or PET-CT scan can be used instead of contrast-enhanced CT. Preventive measures should be applied when appropriate substitute to CT is not available or not diagnosed (minimum necessary dose of ICP, interruption of some treatments and prior hydration). These recommendations formalized by the European Society of Urogenital Radiology (ESUR) in 2018 address most situations faced by clinicians. In complex situations, an opinion from a nephrologist remains necessary after asking the radiologist about the availability of acceptable substitutes.

The aim was to evaluate the prognostic role of sub-categories of ISUP 4 prostate cancer (PCa) on final pathology, and assess the tumor architecture prognostic role for predicting biochemical recurrence (BCR) after radical prostatectomy.From a prospectively-maintained database, we included 370 individuals with ISUP 4 on final pathology. The main outcomes were to evaluate the relationship between different ISUP patterns within the group 4 with pathological and oncological outcomes. Binary logistic regression and Kaplan-Meier estimator were used to evaluate the role of the different categories (3 + 5, 4 + 4, 5 + 3) and tumor architecture (intraductal and/or cribriform) on pathological and oncological outcomes.Among the 370 individuals with ISUP considered for the study, 9, 85 and 6% had grade 3 + 5, 4 + 4 and 5 + 3 PCa, respectively. Overall, 74% had extracapsular extension, while lymph node invasion (LNI) was documented in 9%. A total of 144 patients experienced BCR during follow-up. After adjusting for PSA, pT, grade group, LNI and positive surgical margins (PSM), grade 3 + 5 was a protective factor (HR: 0.30, 95% CI: 0.13,0.68, p = 0.004) in predicting BCR relative to grade 4 + 4. Intraductal or cribriform architecture was correlated with BCR (HR: 5.99, 95% CI: 2.68, 13.4, p 0.001) after adjusting for PSA, pT, grade group, LNI and PSM.Patients with tumor grade 3 + 5 had better pathological and prognostic outcomes compared to 4 + 4 or 5 + 3. When accounting for tumor architecture, the sub-stratification into subgroups lost its prognostic role and tumor architecture was the sole predictor of poorer prognosis in terms of biochemical recurrence.

159 Background: Abiraterone acetate (ABI) improves survival in mCRPC. In a previous observational study, worse PSA response and shorter progression-free survival (PFS) were associated with mean ABI plasma through concentration (ABI Cmin) < 8.5 ng/mL within the first three months (ms) of treatment (Carton E et al. Eur J Cancer 2017). The OPTIMABI study, a multicenter non-randomized study (NCT 03458247), aimed to investigate whether a dose escalation of ABI improve PFS in underexposed progressive mCRPC pts. Methods: In step 1, pts with docetaxel-naive progressive mCRPC received ABI at the standard dose of 1000 mg/d + Prednisone 10 mg/d. Mean ABI Cmin was calculated from three monthly dosages. Pts experiencing progression within the first 6 ms and for whom mean ABI Cmin was < 8.5 ng/mL were included in step 2 and received 1000 mg twice daily (2000 mg/d) of ABI. ABI Cmin was assessed every month. The primary endpoint was the non-progression rate at 12 weeks in step 2. Identification of risk factors of 6 ms-PFS was done using Cox regression analysis. Results: From 06/2018 to 09/2021, 81 of 93 pts (median age: 72 yrs) included in step 1 were evaluable for statistical analysis. The median ABI Cmin was 10.0 (IQR: 4.5-15. 0) ng/mL over the first three ms. Inter-individual variability was 59%. The 6 ms-PFS was 68% (IC 95%: 56% - 80%) with no statistical difference between pts with mean ABI Cmin ≥ or < 8.5 ng/mL (log-rank test, p= 0.24). In multivariate analysis, liver metastasis (Hazard ratio, HR = 5.95, CI95% = 1.22–28.92; p=0.027) and creatinine clearance < 60 mL/min (HR = 3.51, CI95% = 1.12–10.99; p=0.031) were independently associated with 6 ms-PFS. Among 21 pts (25.9%), with mean ABI Cmin < 8.5 ng/mL, 8 pts (38.1%) experienced tumor progression within the first 6 ms; four of them could be included in step 2. None of them fulfilled the primary endpoint despite a significant increase in plasma ABI Cmin (p

Despite an expected increase in prostate cancer (PCa) incidence in the renal transplant recipient (RTR) population in the near future, robot-assisted radical prostatectomy (RARP) in these patients has been poorly detailed. It is not well understood whether results are comparable to RARP in the non-RTR setting.To describe the surgical technique for RARP in RTR and report results from our multi-institutional experience.This was a retrospective review of the experience of four referral centers.Transperitoneal RARP with pelvic lymph node dissection in selected patients.We measured patient, PCa, and graft baseline features; intraoperative and postoperative parameters; complications, (Clavien classification); and oncological and functional outcomes.We included 41 men. The median age, American Society of Anesthesiologists score, preoperative renal function, and prostate-specific antigen were 60 yr (interquartile range [IQR] 57-64), 2 points (IQR 2-3), 45 ml/min (IQR 30-62), and 6.5 ng/ml (IQR 5.2-10.2), respectively. Four men (9.8%) had a biopsy Gleason score7. The majority of the patients (70.7%) did not undergo lymphadenectomy. The median operating time, hospital stay, and catheterization time were 201 min (IQR 170-250), 4 d (IQR 2-6), and 10 d (IQR 7-13), respectively. At final pathology, 11 men had extraprostatic extension and seven had positive surgical margins. At median follow-up of 42 mo (IQR 24-65), four men had biochemical recurrence, including one case of local PCa persistence and one local recurrence. No metastases were recorded while two patients died from non-PCa-related causes. Continence was preserved in 86.1% (p not applicable) and erections in 64.7% (p = 0.0633) of those who were continent/potent before the procedure. Renal function remained unchanged (p = 0.08). No intraoperative complications and one major (Clavien 3a) complication were recorded.RARP in RTR is safe and feasible. Overall, operative, oncological, and functional outcomes are comparable to those described for the non-RTR setting, with graft injury remaining undescribed. Further research is needed to confirm our findings.Robot-assisted removal of the prostate is safe and feasible in patients who have a kidney transplant. Cancer control, urinary and sexual function results, and surgical complications seem to be similar to those for patients without a transplant, but further research is needed.

International audience; Despite recent improvements in survival, metastatic castration-resistant prostate cancers (mCRPCs) remain lethal. Alterations in genes involved in the homologous recombination repair (HRR) pathway are associated with poor prognosis. Poly-ADP-ribose polymerase (PARP) inhibitors (PARPis) have demonstrated anti-tumoral effects by synthetic lethality in patients with mCRPCs harboring HRR gene alterations, in particular BRCA2. While both olaparib and rucaparib have obtained government approvals for use, the selection of eligible patients as well as the prescription of these treatments within the clinical urology community are challenging. This review proposes a brief review of the rationale and outcomes of PARPi treatment, then a pragmatic vision of PARPi use in terms of prescription and the selection of patients based on molecular screening, which can involve potential genetic counseling in the case of associated germinal alterations.

The effect of prostate artery embolization (PAE) on male sexual function is currently the subject of debate in the literature. The main purpose of this study was to define changes in all domains of sexual activity after PAE, using the international index of erectile function score (IIEF-15). A single-center retrospective study was conducted on 129 patients (mean age of 65.5 ± 7 years), who underwent PAE from February 2014 to January 2017 for symptomatic benign prostatic hyperplasia (BPH). Fifty consecutive patients fulfilling the inclusion criteria were evaluated before and after PAE follow-up using the IIEF-15, IPSS, prostate volume (PV) and cardiovascular risk factor and BPH drugs. The IIEF-15 domains analyzed were: erectile function (EF) ejaculation and orgasm (Ej/O), sexual desire (SD), intercourse satisfaction (IS) and overall satisfaction (OS). A paired sample t test or Wilcoxon signed-rank test was used to compare IIEF-15 between baseline and follow-up. The study showed nonsignificant change in IIEF-15 total score (58.0 ± 13.8 SD; p = 0.71) and the five domains (EF 24.5 ± 7.0 SD, p = 0.82; EJ/O 8.2 ± 2.3 SD, p = 0.50; SD 7.2 ± 2.7 SD, p = 0.57; IS 10.3 ± 3.0 SD, p = 0.77; OS 8.2 ± 2.7 SD; p = 0.11) after PAE. We also found a significant improvement in IPSS score after PAE. Based on the IIEF-15 questionnaire, PAE was showed to allow good urinary symptoms results and no deterioration in sexual function.

The aim of this study was to compare observation and early drainage by ureteral stenting in patients with blunt renal trauma and urinary extravasation.A retrospective national multicenter study was performed including all patients admitted for renal trauma at 17 hospitals between 2005 and 2015. Patients presenting with a urinary extravasation on initial imaging were considered for inclusion. Patients were divided in two groups according to the initial approach: observation vs. early drainage by ureteral stent (within 48 h after admission). The primary endpoint was the persistence of urinary extravasation on follow-up imaging.Out of 1799 patients with renal trauma, 238 were included in the analysis (57 in the early drainage and 181 in the observation group). In the early drainage group, 29 patients had persistent urinary extravasation vs. 77 in the observation group (50.9% vs. 42.5%; p value = 0.27). The rates of secondary upper urinary tract drainage did not differ significantly between the early drainage group (26.4%) and the observation group (16%) (p = 0.14). There were no statistically significant differences between the two groups in terms of secondary nephrectomy (0% vs. 2.8%; p = 0.34), and death from trauma (0% vs. 1.8%; p = 0.99). In multivariate analysis, early drainage remained not statistically associated with persistence of urinary extravasation on follow-up imaging (OR = 1.35; p = 0.36) CONCLUSION: In this multicenter cohort, observation was not different from early drainage in terms of persistent urinary extravasation after grade IV blunt renal trauma. Further randomized controlled prospective trials are needed to confirm these findings.

Laparoscopic living-donor nephrectomy (LLDN) is the gold-standard procedure for kidney procurement. Ipsilateral orchialgia has barely been described. Some authors reported that ligation of gonadal vein (GV) above iliac vessel bifurcation could prevent orchialgia. We aimed to assess incidence and duration of orchialgia after LLDN in male donors despite distal ligation of GV. Patients who underwent LLDN from 2014 to 2017 were included. Standard procedure consisted in distal ligation of GV, close to the renal vein confluence and proximal ureteral ligation. Patients’ demographics, per-operative data, and post-operative consultation reports were retrospectively reviewed. Orchialgia and scrotal symptoms were assessed through a non-validated questionnaire by phone interview. Sixty-nine donors were included. Orchialgia incidence and testicular swelling were 31.9% (n = 22) and 15.9% (n = 11), respectively. Median symptom duration was 15.5 months. Orchialgia led to medical consultation in 41.7% (n = 10) of cases. All patients declared having been informed, prior to donation, about possible residual pain but not specifically orchialgia. Orchialgia after LLDN affects more than 30% of donors, despite distal ligation of GV and led less than 50% of them to medical consultation, suggesting a large underestimation in clinical practice. Emphasis should be put on this complication during pre-donation information.

The diagnosis of prostate cancer (PCa) can be challenging due to the limited performance of current diagnostic tests, including PSA, digital rectal examination and transrectal conventional US. Multiparametric MRI has improved PCa diagnosis and is recommended prior to biopsy; however, mp-MRI does miss a substantial number of PCa. Advanced US modalities include transrectal prostate elastography and contrast-enhanced US, as well as improved B-mode, micro-US and micro-Doppler techniques. These techniques can be combined to define a novel US approach, multiparametric US (mp-US). Mp-US improves PCa diagnosis but is not sufficiently accurate to obviate the utility of mp-MRI. Mp-US using advanced techniques and mp-MRI provide complementary information which will become even more important in the era of focal therapy, where precise identification of PCa location is needed.

Introduction The purpose of this study was to assess oncologic and functional outcomes of both percutaneous ablation (cryoablation and radiofrequency ablation) and robot-assisted partial nephrectomy (RAPN) in the treatment of renal tumors larger than 4 cm. Materials and Methods We retrospectively analyzed prospectively collected data from 102 consecutive patients, who underwent minimally invasive treatment for cT1b renal tumors at our institution. Primary renal function outcome was assessed by estimated glomerular filtration rate preservation at baseline and 1 year postoperatively. Perioperative data and functional and oncologic outcome were collected. Multivariate regression models were used to compare functional outcomes between groups. Cancer-specific survival and recurrence-free survival were estimated at 2 years using the Kaplan-Meier method and compared with Cox proportional hazards regression model to calculate hazard ratios (HRs). To control for selection bias between the different treatments, we adjusted our models with an inverse probability of treatment weighting propensity score. Results There was no significant difference in renal preservation between the groups (P = .664). Multivariate analysis did not show a statistically significant difference in terms of renal function outcomes between the RAPN and percutaneous thermal ablation groups. The adjusted HR regarding the local recurrence-free survival was significantly shorter for the cryoablation group (HR, 4.3; 95% confidence interval, 1.78-10.37; P = .001). Conclusions Our study demonstrated the equivalence between RAPN and percutaneous ablative techniques for the preservation of renal function in the treatment of T1b tumors. RAPN offers a better local control than percutaneous ablation, in terms of primary success rate.

QTc prolongation is linked to Torsade de Pointes, sudden cardiac death, and overall cardiovascular mortality. 754 prostate cancer patients undergoing brachytherapy were analyzed, prolonged QTc was defined as ���450ms. A prolonged QTc was more frequent (10.1 vs. 5.1%, p = 0.040) in patients with high-risk cancer than in low to intermediate risk patients. The absolute QTc-time was correlated with age (r = 0.125), neutrophil count (r = 0.130) and negatively correlated with the testosterone level (r=���0.205). Treating physicians should be aware of this and monitor the QTc during ADT to possibly decrease cardiac morbidity/mortality in these patients who are more likely to require ADT.

Resume Introduction Les traumatismes renaux sont frequents, retrouves dans 10 % de l’ensemble des traumatismes abdominaux. Ils sont majoritairement fermes, en rapport avec un choc direct ou une deceleration brutale. Materiel et methodes Nous avons une realise une synthese de la prise en charge des traumatismes du rein a destination des infirmieres et infirmiers. Resultats Les signes cliniques les plus frequents sont l’hematurie et la lombalgie. Le meilleur examen diagnostique est l’uroscanner. La classification la plus utilisee est celle de l’American Association for the Surgery of Trauma (AAST) qui classe les traumatismes renaux en 5 grades de gravite croissante sur la base des images scannographiques. Le traitement est conservateur dans l’immense majorite des cas et s’est largement simplifie ces dernieres annees, etant essentiellement base sur une surveillance clinique. Les traitements radio-interventionnels et endoscopiques sont reserves a des cas tres selectionnes et le recours a l’exploration chirurgicale est exceptionnel. Conclusion Le pronostic s’est egalement considerablement ameliore et les traumatismes renaux aboutissent desormais tres rarement au deces ou a la perte du rein.

International audience; Deregulation of the PI3K-Akt-mTOR pathway plays a critical role in the development and progression of many cancers. In prostate cancer, evidence suggests that it is mainly driven by PTEN loss of function. For many years, the development of selective Akt inhibitors has been challenging. In recent phase II and III clinical trials, Ipatasertib and Capivasertib associated with androgen deprivation therapies showed promising outcomes in patients with metastatic castration-resistant prostate cancer and PTEN-loss. Ongoing trials are currently assessing several Akt inhibitors in prostate cancer with different combinations, at different stages of the disease.

Stem and progenitor cells of the adult prostate epithelium have historically been believed to reside mainly or exclusively within the basal cell compartment and to possess basal-like phenotypic characteristics. Within the past decade, evidence of the existence of luminal epithelial cells exhibiting stem/progenitor properties has been obtained by lineage tracing and by functional characterization of sorted luminal-like cells. In 2020, the boom of single-cell transcriptomics led to increasingly exhaustive profiling of putative mouse luminal progenitor cells and, importantly, to the identification of cognate cells in the human prostate. The enrichment of luminal progenitor cells in genetically modified mouse models of prostate inflammation, benign prostate hypertrophy and prostate cancer, and the intrinsic castration tolerance of these cells, suggest their potential role in prostate pathogenesis and in resistance to androgen deprivation therapy. This Review bridges different approaches that have been used in the field to characterize luminal progenitor cells, including the unification of multiple identifiers employed to define these cells (names and markers). It also provides an overview of the intrinsic functional properties of luminal progenitor cells, and addresses their relevance in mouse and human prostate pathophysiology.

Simple Summary Radiotherapy may have an interesting role of reinforcing the loco-regional control of cancer, in addition to surgery, when used as a preoperative treatment. This sequence has demonstrated its efficacy and safety in various malignancies, but no strong data exist in the era of uro-oncology. In this review article, we aim to highlight the potential usefulness of preoperative radiotherapy in prostate and muscle-invasive bladder cancer, aiming to enhance pathological response and local control and to prevent intraoperative tumor seeding. We also emphasize the need for further clinical studies assessing the functional safety of subsequent surgical procedures in a competitive context of new systemic agents that have proven to demonstrate a survival benefit in locally advanced urologic cancers. Abstract Preoperative radiotherapy (RT) is commonly used for the treatment of various malignancies, including sarcomas, rectal, and gynaecological cancers, but it is preferentially used as a competitive treatment to radical surgery in uro-oncology or as a salvage procedure in cases of local recurrence. Nevertheless, preoperative RT represents an attractive strategy to prevent from intraoperative tumor seeding in the operative field, to sterilize microscopic extension outside the organ, and to enhance the pathological and/or imaging tumor response rate. Several clinical works support this research field in uro-oncology. In this review article, we summarized the oncologic impact and safety of preoperative RT in localized prostate and muscle-invasive bladder cancer. Preliminary studies suggest that both modalities can be complementary as initial primary tumor treatments and that a pre-operative radiotherapy strategy could be beneficial in a well-defined population of patients who are at a very high-risk of local relapse. Future prospective trials are warranted to evaluate the oncologic benefit of such a combination of local treatments in addition to new life-prolonging systemic therapies, such as immunotherapy, and new generation hormone therapies. Moreover, the safety and the feasibility of salvage surgical procedures due to non-response or local recurrence after pelvic RT remain poorly evaluated in that context.