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Prostate cancer (PCa) is the most frequently diagnosed cancer in men in Europe. The impact of PCa natural history and therapeutic management on the outcomes of castration-resistant prostate cancer patients with metastasis (mCRPC) remains unclear.The objective of this study was to describe retrospectively patterns of clinical progression through diagnosis sequences before the mCRPC stage and to assess how these sequences impacted patients' disease progression and overall survival at mCRPC stage.Patients with mCRPC were identified from the Prostate Cancer Registry (PCR), an observational study in a real-world setting in 16 countries between 2013 and 2016. Patients were grouped in diagnosis sequences before mCRPC and defined by date of PCa diagnosis, first metastasis, and castration resistance. Distribution of time-to-event variables were estimated using Kaplan-Meier product-limit survival curves for overall survival (OS) and progression-free survival (PFS). Non-adjusted Cox models were conducted for efficacy endpoints (OS, PFS) to estimate hazard ratios between diagnosis sequences.At the end of study, 2859 mCRPC patients were included in this analysis. Among mCRPC four diagnosis sequences were identified: 35% developed metastases (mHSPC) before becoming castration resistant (sequence 1, metachronous mHSPC), 10% developed castration resistance (nmCRPC) before metastases (sequence 2), 27% developed metastases and castration resistance within 4 months (sequence 3) and 28% of patients were de novo mHSPC (sequence 4). Median OS was 17.7 months (interquartile range (IQR): 8.8-29.9) and PFS was 6.4 months (IQR: 3.2-12.0). The univariate analyses showed no correlation between mCRPC patients' OS or PFS and the diagnosis sequence.This large European study describe four different patterns of prostate cancer progression to mCRPC stage. Our results indicate that patient survival becomes comparable after progression to mCRPC, regardless of the diagnosis sequence.ClinicalTrials.gov identifier NCT02236637; registered September 2014.

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.

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

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

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.

Background The CARMENA trial in patients with metastatic renal cell carcinoma (mRCC) demonstrated that treatment with sunitinib alone was noninferior to cytoreductive nephrectomy (CN) followed by sunitinib (nephrectomy⬜sunitinib). Objective The objective of this study was to provide updated overall survival (OS) outcomes of CARMENA and assess whether some subgroups may still benefit from upfront CN. Design, setting, and participants CARMENA was a phase III trial in 450 patients with mRCC enrolled from 2009 to 2017. Intervention Patients in the intention-to-treat population received nephrectomy⬜sunitinib (standard of care [SOC]; n = 226) or sunitinib alone (n = 224). Outcome measurements and statistical analysis Primary endpoint was OS, assessed using an updated data cut-off (October 2018; median OS event-free follow-up, 36.6 mo). Patients were reclassified by risk using International Metastatic RCC Database Consortium (IMDC) criteria. Results and limitations Sunitinib alone was noninferior to nephrectomy⬜sunitinib (hazard ratio [HR], 0.97; 95% confidence interval, 0.79⬜1.19; p = 0.8) and demonstrated longer median OS (19.8 mo vs 15.6 mo, respectively). For patients with two or more IMDC risk factors, OS was significantly longer with sunitinib alone than with nephrectomy⬜sunitinib (31.2 mo vs 17.6 mo, respectively; HR, 0.65; p = 0.03). For patients with one IMDC risk factor, OS was longer for nephrectomy⬜sunitinib versus sunitinib alone although not significantly (31.4 mo vs 25.2 mo; HR, 1.30; p = 0.2). The post hoc nature of the subgroup analyses may limit their interpretation. Conclusions Sunitinib alone was noninferior compared with nephrectomy⬜sunitinib, suggesting that CN should not be considered SOC in patients with mRCC requiring systemic treatment. Certain subgroups, including patients with one IMDC risk factor, may still benefit from upfront CN. Patient summary We assessed the survival of patients with metastatic kidney cancer in a clinical trial. Patients treated with sunitinib on its own had the same survival as patients who had surgery before sunitinib treatment. We conclude that surgery may not be necessary for some patients with metastatic kidney cancer.

Background Due to increased risk of pyelonephritis, patients with intestinal reconstruction of the lower urinary tract (IRLUT) have long been advised against kidney transplantation. The aim of this study was to compare the outcomes of transplantation between patients with IRLUT and patients with normal LUT (NLUT) using propensity score matching method. Methods The study included 23 kidney recipients with IRLUT matched to 46 kidney recipients with NLUT using known allograft survival and pyelonephritis risk factors as covariates. One‐, 5‐, and 10‐year graft survival, pyelonephritis, and surgical complications occurrence and graft function were compared. Results One‐, 5‐, and 10‐year graft survival were 96%, 91%, and 63% in the IRLUT group and 96%, 88%, and 70% in the NLUT group, respectively (p = 0.72). Patients with IRLUT had increased cumulative risk of pyelonephritis at 10 years (70% vs. 19%; log‐rank

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 To assess the impact of expanded criteria donors (ECD) on urinary complications in kidney transplantation. PATIENTS AND METHODS The UriNary Complications Of Renal Transplant (UNyCORT) is a cohort study based on the French prospective Donnees Informatisees et VAlidees en Transplantation/Computerized and VAlidated Data in Transplantation (DIVAT) cohort. Data were extracted between 1 January 2002 and 1 January 2018 with 1-year minimum follow-up, in relation to 44 pre- and postoperative variables. ECD status was included according to United Network for Organ Sharing (UNOS) definition. The primary outcome of the UNyCORT study was the association between the donor's ECD/standard criteria donors (SCD) status and urinary complications at 1 year in uni- and multivariate analysis. Sub-group analysis, stratified analysis on ECD/SCD donor's status and transplant failure analysis were then conducted. RESULTS Between 1 January 2002 and 1 January 2018, 10 279 kidney transplants in adult recipients were recorded within the DIVAT network. A total of 8559 (83.4%) donors were deceased donors and 1699 (16.6%) were living donors (LD). Among donation after circulatory death (DCD) donors, 224 (2.85%) were uncontrolled DCD and 93 (1.09%) were controlled DCD donors. A total of 3617 (43.9%) deceased donors were ECD. The overall urological complication rate was 16.26%. The donor's ECD status was significantly associated with an increased risk of urological complications at 1 year in multivariate analysis (odds ratio: 1.50, 95% CI 1.31-1.71; P

The main objective of static cold storage is to reduce cellular metabolic demands to extend the period of ischaemia prior to transplantation. Hypothermia does not halt metabolism and the absence of oxygen causes a cellular shift toward anaerobic respiratory pathways. There is emerging evidence that the introduction of oxygenation during organ preservation may help ameliorate the degree of ischaemia reperfusion injury and improve post-transplantation outcomes. This review aims to appraise and summarise all published literature that utilises oxygenation to improve kidney preservation for purposes of transplantation. We performed a scoping review of the literature using the bibliographic databases Embase and MEDLINE. The final date for searches was 20 March 2021. All research studies included were those that reported oxygen delivery during kidney preservation as well as providing a description of the oxygenation technique. 17 human and 48 animal studies met the inclusion criteria. The oxygen delivery methods investigated included hypothermic oxygenated machine perfusion (HOPE), oxygen carriers, two-layer method, venous systemic persufflation, hyperbaric oxygenation, normothermic machine perfusion and sub-normothermic machine perfusion. The COMPARE trial was the only study carried out with the most methodological robustness being a randomised, double blind, controlled, phase III trial that investigated the efficacy of HOPE versus HMP. A variety of studies reflect the evolution of oxygenation with useful lessons and encouraging outcomes. The first in human studies investigating HOPE and oxygen carriers are most robustly investigated strategies for oxygenation during kidney preservation and are, therefore, the best clinical references.

Belatacept may increase cytomegalovirus (CMV) disease risk after conversion from CNI-based therapy. We analyzed CMV disease characteristics after belatacept conversion. Propensity score matching was used to compare CMV disease incidence in belatacept- and CNI-treated kidney transplant recipients (KTRs). CMV disease characteristics and risk factors under belatacept were analyzed. In total, 223 KTRs (median age [IQR] 59.2 years [45.4-68.5]) were converted to belatacept (median of 11.5 months [2.5-37.0] post-transplantation); 40/223 (17.9%) developed CMV disease. Independent risk factors included increased age (p = .0164), D+/R- CMV serostatus (p = .0220), and low eGFR at conversion (p = .0355). Among 181 belatacept-treated patients matched to 181 controls, 32/181 (17.7%) experienced CMV disease (vs. 5/181 controls [2.8%]). CMV disease cumulative incidences were 6.33 and 0.91/100 person-years (p-y) in belatacept and control groups, respectively. CMV disease risk was particularly high in elderly patients (converted >70 years) and those with eGFR

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.

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.

Biphasic squamoid alveolar papillary renal cell carcinoma (BSA-PRCC) is a recently studied lesion considered a morphologic variant of papillary renal cell carcinoma (RCC), more closely related to type 1. Considering the role of proto-oncogene MET in both sporadic type 1 papillary RCC and hereditary papillary RCC, we aimed to explore the role of MET activation in the oncogenesis of BSA-PRCC. We identified 17 patients with either unique (n = 14) or multiple (n = 3) BSA-PRCC, all localized, and performed an integrative analysis of MET status in 18 formalin-fixed paraffin-embedded tumors combining next-generation sequencing analysis, fluorescent in situ hybridization and immunohistochemistry. Trisomy 7 was found in 86% of tumors (14/16) without MET amplification at 7q31 (15/15). A pathogenic MET genetic variant was identified in 60% (9/15) of cases, at the germline level in 57% (4/7) of tested patients or at the somatic level (5/11). MET expression was observed in all tumors with a higher value of combined score in large cells (mean 97%, range 80–100%) than in small cells (mean 74%, range 10–100%) and was lower in two cases without MET copy number gain. In conclusion, our study provides additional evidence to consider biphasic squamoid alveolar papillary RCC as a morphological variant of type 1 papillary renal RCC. Our data strongly suggest that MET represents a major oncogenic driver gene in BSA-PRCC, harboring a higher frequency of MET mutation that encourages to further explore the benefice of anti-MET targeted therapies for aggressive BSA-PRCC.

Resume Objectif Proposer des recommandations pour la prise en charge des symptomes du bas appareil urinaire (SBAU) et de l’incontinence urinaire du patient transplante renal et du candidat a la transplantation renale. Methode Une revue de la litterature (Medline) avec approche systematique a ete conduite par le CTAFU concernant les modalites therapeutiques des SBAU et des troubles de la continence du patient transplante renal et du candidat a la transplantation renale, en evaluant les references et leur niveau de preuve. Resultats La capacite vesicale fonctionnelle et la compliance vesicale sont alterees lors de la dialyse. Les SBAU, lies aux alterations pre-transplantation renale, s’ameliorent le plus frequemment spontanement apres transplantation renale. Les SBAU lies a une hyperplasie benigne de prostate (HBP) peuvent etre masques en pre-transplantation en raison de l’oligurie, des troubles de la compliance et de la capacite vesicale. En cas de SBAU lies a une HBP, seuls les anticholinergiques necessitent une adaptation de la posologie en fonction de la clairance de la creatinine. Si indiquee, la chirurgie de l’HBP peut etre realisee precocement apres transplantation renale. Concernant la prise en charge chirurgicale de l’incontinence urinaire, il ne semble pas exister d’augmentation des complications infectieuses chez le patient transplante renal. Une attention particuliere doit etre portee a la prise en charge du residu post mictionnel et des pressions vesicales en cas de vessie neurologique. La prise en charge adaptee d’un patient presentant une vessie neurologique permet une transplantation renale sans augmentation du risque de perte du transplant renal, au prix d’une augmentation de l’incidence des infections urinaires febriles. Conclusion Ces recommandations francaises doivent contribuer a ameliorer la prise en charge des symptomes du bas appareil urinaire et de l’incontinence urinaire du patient transplante renal et du candidat a la transplantation renale.

Resume Objectif Proposer des recommandations pour la prise en charge du carcinome urothelial du patient transplante renal et du candidat a la transplantation renale. Methode Une revue de la litterature (Medline) d’approche systematique a ete conduite par le CTAFU concernant l’epidemiologie, le depistage, le diagnostic et le traitement du carcinome urothelial du patient transplante renal et du candidat a la transplantation renale en evaluant les references et leur niveau de preuve. Resultats L’incidence des carcinomes urotheliaux du patient transplante renal est 3 fois plus elevee que l’incidence des carcinomes urotheliaux de la population generale. Les principaux facteurs de risque de carcinomes urotheliaux du patient transplante renal sont identiques a ceux de la population generale. La nephropathie a l’acide aristolochique et l’infection a BK virus sont des facteurs de risques plus frequents du patient transplante renal. En comparaison avec la population generale, a stade equivalent, les TVNIM du patient transplante renal sont associees a un taux de recidive plus eleve et a une recidive plus precoce, La tolerance et l’efficacite des traitements adjuvants intra-vesicaux (Mitomycine C et BCG) ont ete rapportees par des series retrospectives. Le traitement de reference des TVIM localisees du patient transplante renal est la chirurgie d’exerese carcinologique. Chez le candidat a une transplantation renale avec antecedent de tumeur urotheliale, il est recommande de realiser imperativement les cystoscopies de suivi selon la frequence recommandee en fonction du risque de recidive et de progression de la TVNIM et de maintenir ce suivi a une frequence au moins semestrielle jusqu’a la transplantation quel que soit le niveau de risque de recidive et de progression. Les donnees actuelles permettent de proposer des delais de contre-indication temporaire apres traitement d’une tumeur urotheliale, selon un avis d’expert. Conclusion Ces recommandations francaises doivent contribuer a ameliorer la prise en charge du carcinome urothelial du patient transplante renal et du candidat a la transplantation renale en integrant les objectifs oncologiques avec l’acces a la transplantation.

OBJECTIVE To propose recommendations for the management of renal cell carcinomas (RCC) of the renal transplant. METHOD Following a systematic approach, a review of the literature (Medline) was conducted by the CTAFU to evaluate prevalence, diagnosis and management of RCC arousing in the renal transplant. References were assessed according to a predefined process to propose recommendations with levels of evidence. RESULTS Renal cell carcinomas of the renal transplant affect approximately 0.2% of recipients. Mostly asymptomatic, these tumors are mainly diagnosed on a routine imaging of the renal transplant. Predominant pathology is clear cell carcinomas but papillary carcinomas are more frequent than in general population (up to 40-50%). RCC of the renal transplant is often localized, of low stage and low grade. According to tumor characteristics and renal function, preferred treatment is radical (transplantectomy) or nephron sparing through partial nephrectomy (open or minimally invasive approach) or thermoablation after percutaneous biopsy. Although no robust data support a switch of immunosuppressive regimen, some authors suggest to favor the use of mTOR inhibitors. CTAFU does not recommend a mandatory waiting time after transplantectomy for RCC in candidates for a subsequent renal tranplantation when tumor stage

Resume Objectif Le but du Comite de transplantation de l’association francaise d’urologie est de proposer des recommandations pour la prise en charge du carcinome a cellules renales du rein natif (CCRN) chez le receveur d’un transplant renal et du carcinome a cellules renales (CCR) du patient malade renal chronique terminal (MRCT) candidat a une transplantation renale (TR). Methode Une revue d’approche systematique de la litterature (Medline) a ete conduite par le CTAFU concernant l’epidemiologie, le diagnostic et le traitement du CCRN chez le receveur d’un transplant renal et du CCR chez le MRCT en evaluant les references et leur niveau de preuve. Resultats L’incidence standardisee du CCR chez le MRCT est 4,5 fois superieure a la population generale. Le CCRN concernerait 1 a 3 % des patients transplantes avec un risque 10 a 15 fois plus eleve que la population generale. Ce risque est majore en cas de maladie renale multi-kystique acquise. Les differentes series s’accordent sur l’interet d’une imagerie annuelle de l’appareil urinaire natif par echographie. Le traitement du CCR chez le MRCT et du CCRN chez le transplante renale repose sur une prise en charge chirurgicale par nephrectomie elargie par voie ouverte ou cœlioscopie. La surveillance est une option valide pour les tumeurs kystiques ou de petite taille. La prise en charge des formes localisees ne necessite aucune modification dans le traitement de fond immunosuppresseur sauf pour les patients sous inhibiteurs de mTOR compte tenu des donnees montrant un taux plus eleve de complications chirurgicales. Le CTAFU ne recommande pas de delai de carence apres traitement d’un CCR localise chez un patient MRCT et candidat a une transplantation renale si la tumeur est de stade Conclusion Ces recommandations francaises doivent contribuer a ameliorer la prise en charge du CCRN chez le patient transplante renal et CCR chez le candidat a une transplantation renale en integrant les objectifs oncologiques dans le contexte de transplantation renale.

Resume Objectif Le but du Comite de transplantation de l’Association francaise d’urologie est de proposer des recommandations pour la prise en charge du cancer de la prostate localise (CaP) chez le candidat ou le receveur d’un transplant renal. Methode Une revue de la litterature d’approche systematique (Medline) a ete conduite par le CTAFU concernant l’epidemiologie, le depistage, le diagnostic et le traitement du CaP chez le candidat ou le receveur d’un transplant renal en evaluant les references et leurs niveaux de preuve. Resultats L’incidence du CaP chez le transplante renal est similaire a la population generale. Le depistage dans cette population doit suivre les recommandations du CCAFU. Le depistage est systematique chez le candidat a un transplant renal de plus de 50 ans. Le diagnostic repose sur les biopsies de la prostate realisees apres IRM multiparametrique et sans specificite de l’antibioprophylaxie. Les recommandations therapeutiques du CaP proposees par le CCAFU restent applicables a la population des patients transplantes avec certaines specificites en particulier pour le traitement des aires ganglionnaires. Pour les candidats a la transplantation renale, la problematique de l’acces a la transplantation doit etre prise en compte. Les donnees actuelles permettent de proposer des delais de carence apres traitement du CaP avec un faible niveau de preuve. Conclusion Ces recommandations francaises doivent contribuer a ameliorer la prise en charge du CaP chez le patient candidat ou receveur d’un transplant renal en integrant objectifs oncologiques et acces a la transplantation.

Resume Objectif Proposer des recommandations pour la prise en charge des calculs urinaires chez le donneur ou le receveur d’un transplant renal. Methode Une revue d’approche systematique de la litterature (Medline) a ete conduite par le CTAFU concernant l’epidemiologie, le diagnostic et le traitement des calculs urinaires chez le donneur ou le receveur d’un transplant renal. Resultats La prevalence des calculs urinaires est inconnue chez les donneurs decedes mais peut atteindre 9,3 % chez les donneurs vivants dans les pays industrialises. Chez tous types de donneurs de reins, hormis ceux de la categorie 2 de Maastricht, le diagnostic repose sur la tomodensitometrie faisant partie du bilan avant tout prelevement d’organes en France. Aucune etude n’a compare les strategies de traitements envisageables en cas de calcul detecte chez le donneur : l’ureteroscopie ou la lithotripsie extracorporelle chez le donneur vivant avant prelevement, un traitement ex vivo (pyelotomie ou ureteroscopie), une ureteroscopie chez le receveur apres transplantation, une surveillance en cas de petit calcul. Les calculs de novo chez le receveur impliquent un processus de lithogenese a identifier et traiter pour eviter les recidives. Le contexte de rein unique fonctionnel fait toute la gravite de la pathologie lithiasique. Le diagnostic est en general fait au decours d’un bilan pour alteration de la fonction renale, d’une hematurie ou d’un sepsis. L’echographie detecte la dilatation des cavites pyelocalicielles, le scanner precise la topographie et la taille du calcul. Il n’existe aucune etude prospective comparative evaluant les techniques de traitement d’un calcul chez un transplante renal qui sont identiques a celles de la population generale. Conclusion Ces recommandations francaises doivent contribuer a ameliorer la prise en charge des calculs urinaires chez le patient donneur ou receveur d’un transplant renal.

Resume Objectif Proposer des recommandations chirurgicales pour la nephrectomie dans le cadre d’un don de rein pour transplantation. Methode Une revue de la litterature (Medline) avec approche systematique a ete conduite par le CTAFU concernant les elements d’evaluation fonctionnelle et anatomique du candidat au don, les options dans le choix du rein a prelever et des differentes techniques chirurgicales, en evaluant les references et leur niveau de preuve. Resultats Les recommandations precisent le cadre legal et reglementaire du don de rein. Une evaluation de qualite du candidat au don est un des prerequis indispensable a la securite du donneur qui est une priorite absolue. L’impact de la nephrectomie sur la fonction renale doit etre evalue. En cas de vascularisation modale des deux reins sans difference relative de fonction ni anomalie urologique, le rein gauche doit etre preleve afin d’avoir une veine plus longue. Les techniques chirurgicales de nephrectomie mini-invasives ont pour avantages une recuperation plus rapide, une hospitalisation plus courte et une diminution des douleurs pour le donneur. Ces techniques mini-invasives doivent etre proposees a la place d’une voie incisionnelle ouverte. Conclusion Ces recommandations francaises doivent contribuer a ameliorer la prise en charge chirurgicale des patients candidats a un don de rein.

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.

Summary Background Whether multiparametric MRI improves the detection of clinically significant prostate cancer and avoids the need for systematic biopsy in biopsy-naive patients remains controversial. We aimed to investigate whether using this approach before biopsy would improve detection of clinically significant prostate cancer in biopsy-naive patients. Methods In this prospective, multicentre, paired diagnostic study, done at 16 centres in France, we enrolled patients aged 18–75 years with prostate-specific antigen concentrations of 20 ng/mL or less, and with stage T2c or lower prostate cancer. Eligible patients had been referred for prostate multiparametric MRI before a first set of prostate biopsies, with a planned interval of less than 3 months between MRI and biopsies. An operator masked to multiparametric MRI results did a systematic biopsy by obtaining 12 systematic cores and up to two cores targeting hypoechoic lesions. In the same patient, another operator targeted up to two lesions seen on MRI with a Likert score of 3 or higher (three cores per lesion) using targeted biopsy based on multiparametric MRI findings. Patients with negative multiparametric MRI (Likert score ≤2) had systematic biopsy only. The primary outcome was the detection of clinically significant prostate cancer of International Society of Urological Pathology grade group 2 or higher (csPCa-A), analysed in all patients who received both systematic and targeted biopsies and whose results from both were available for pathological central review, including patients who had protocol deviations. This study is registered with ClinicalTrials.gov, number NCT02485379, and is closed to new participants. Findings Between July 15, 2015, and Aug 11, 2016, we enrolled 275 patients. 24 (9%) were excluded from the analysis. 53 (21%) of 251 analysed patients had negative (Likert ≤2) multiparametric MRI. csPCa-A was detected in 94 (37%) of 251 patients. 13 (14%) of these 94 patients were diagnosed by systematic biopsy only, 19 (20%) by targeted biopsy only, and 62 (66%) by both techniques. Detection of csPCa-A by systematic biopsy (29·9%, 95% CI 24·3–36·0) and targeted biopsy (32·3%, 26·5–38·4) did not differ significantly (p=0·38). csPCa-A would have been missed in 5·2% (95% CI 2·8–8·7) of patients had systematic biopsy not been done, and in 7·6% (4·6–11·6) of patients had targeted biopsy not been done. Four grade 3 post-biopsy adverse events were reported (3 cases of prostatitis, and 1 case of urinary retention with haematuria). Interpretation There was no difference between systematic biopsy and targeted biopsy in the detection of ISUP grade group 2 or higher prostate cancer; however, this detection was improved by combining both techniques and both techniques showed substantial added value. Thus, obtaining a multiparametric MRI before biopsy in biopsy-naive patients can improve the detection of clinically significant prostate cancer but does not seem to avoid the need for systematic biopsy. Funding French National Cancer Institute.

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.

Resumen Este articulo presenta una actualizacion sobre los aspectos tecnicos de la cirugia del donante vivo de rinon. Se ha realizado una busqueda bibliografica exhaustiva a partir de Medline y Embase utilizando las siguientes palabras clave (Medical Subject Headings [MeSH]) solas o en combinacion: «donante vivo; extraccion vaginal; nefrectomia en donante; nefrectomia laparoscopica asistida por robot». Tambien se han consultado los documentos legislativos franceses y estadounidenses. La via laparoscopica se ha impuesto como una via de acceso de referencia. La via asistida por robot esta en fase de desarrollo sin que se hayan demostrado beneficios respecto a las otras tecnicas minimamente invasivas. La via laparoscopica con asistencia manual se utiliza poco en Francia y se asocia a una tasa mas elevada de complicaciones de tipo Clavien I, esencialmente debido a dolor postoperatorio. La cirugia del donante vivo ha experimentado muchos avances tecnicos, sobre todo con procedimientos minimamente invasivos, dirigidos a reducir los efectos secundarios en el donante, a la vez que se mantiene el riesgo de morbilidad mas bajo posible para esta cirugia particular realizada en pacientes sanos.

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.

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; Background: Benign prostatic hyperplasia (BPH) is commonly responsible for lower urinary tract symptoms (LUTS) in men aged 50 or over. Sexual dysfunctions, such as ejaculatory disorders (EjD), go along with LUTS but are frequently overlooked in the initial evaluation. This review aimed to detail BPH-related EjD, as well as their modifications by medical, surgical, and interventional treatments. Methods: We conducted a narrative review looking for publications between 1990 and 2020, regarding physiopathology, epidemiology, evaluation, and therapeutic management (medical, surgical, and interventional) of BPH-related EjD. Results: Sixty-five articles were included in our final analysis. Forty-six percent of men presenting with LUTS reported EjD. If the prevalence increases with age and LUTS severity, the functional impairment is not correlated with age. Several self-questionnaires evaluated the sexual function, but only four approaches are specific to EjD. Medical therapies were exposed to anejaculation, rather than retrograde ejaculation (RE) (4–30% (alpha-blockers), 4–18% (5-alpha-reductase inhibitors)). Regarding surgical therapies, trans-urethral resection of the prostate (TURP) and incision of the prostate (TUIP) are associated with 50–70% and 21–35% of RE. The RE rate is important after open simple prostatectomy but can be reduced with robotic approaches and urethral sparing techniques (19%). Anatomic endoscopic enucleation of the prostate (AEEP) with or without a laser source is associated with an 11–36% RE rate, according to supramontanal preservation. Recent surgical techniques (Rezum©, Aquablation©, or Urolift©) were developed to preserve antegrade ejaculation with promising short-term results. Regardless of the surgical approach, anatomic studies suggest that the preservation of peri-montanal tissue (7.5 mm laterally; 10 mm proximally) is primordial to avoid post-operative RE. Finally, prostate artery embolization (PAE) limits the RE rate but exposes it to a 12 months 10% re-intervention rate. Conclusion: EjD concerns almost half of the patients presenting BPH-related LUTS. Initial evaluation of EjD impairment is primordial before medical or surgical therapy. Peri-montanal tissue preservation represents a key point for antegrade ejaculation preservation, regardless of the surgical option.