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Purpose:Treatment options for the management of upper tract urothelial cancer are based on accurate staging. However, the performance of conventional cross-sectional imaging for clinical lymph node staging (N-staging) remains poorly investigated. This study aims to evaluate the diagnostic accuracy of conventional cross-sectional imaging for upper tract urothelial cancer N-staging.Materials and Methods:This study was a multicenter, retrospective, observational study. We included 865 nonmetastatic (M0) upper tract urothelial cancer patients treated with curative intended surgery and lymph node dissection who had been staged with conventional cross-sectional imaging before surgery. We compared clinical (c) and pathological (p) N-staging results to evaluate the concordance of node-positive (N+) and node-negative (N0) disease and calculate cN-staging's diagnostic accuracy.Results:Conventional cross-sectional imaging categorized 750 patients cN0 and 115 cN+. Lymph node dissection categorized 641 patients pN0 and 224 pN+. The cN-stage was pathologically downstaged in 6.8% of patients, upstaged in 19%, and found concordant in 74%. The sensitivity and specificity of cN-staging were 25% (95% CI 20; 31) and 91% (95% CI 88; 93). Positive and negative likelihood ratios were 2.7 (95% CI 2.0; 3.8) and 0.83 (95% CI 0.76; 0.89). The area under the receiver operating characteristics curve (0.58, 95% CI 0.55; 0.61) revealed low diagnostic accuracy.Conclusions:Conventional cross-sectional imaging had low sensitivity in detecting upper tract urothelial cancer pN+ disease. However, cN+ increased the likelihood of pN+ by almost threefold. Thus, conventional cross-sectional imaging is a rule-in but not a rule-out test. Lymph node dissection should remain the standard during extirpative upper tract urothelial cancer surgery to obtain accurate N-staging. cN+ could be a strong argument for early systemic treatment.

A stoma exposes patients to several complications which could impair their quality of life (QoL). In the last decade, the market for stoma therapy in France has evolved, with a significant increase in the activities of home health providers, meeting a need for patient follow-up and companionship. International studies have demonstrated the impact of the stoma therapist (ST) follow-up on the improvement of an ostomy patient's QoL. However, the impact of home stoma nurse management has not been analysed. In this context we would like to assess the added value on health-related QoL from the enhanced follow-up of ostomy patients by STs.This is a randomized, controlled, open, national and multicentre trial (12 centres) which includes patients with an ostomy who benefit from either standard follow-up or from an enhanced and personalized follow-up with, in particular, regular consultations with an ST after discharge. The primary end-point is the 3-month QoL score obtained from the Stoma-QoL questionnaire. The secondary end-points are satisfaction of the care, comparison of QoL scores (Stoma-QoL and EuroQuol EQ-5D) and the economic gains by calculating the consumption of resources between the two arms. There will be a modified intention-to-treat analysis with 6-month follow-up in both study arms.The StomaCare trial will be the first randomized controlled study in France to evaluate the impact on QoL of an enhanced follow-up at home of ostomy patients by an ST.

Docetaxel and gemcitabine have different mechanisms of action, are well tolerated as monotherapies, and are affordable. This combination represents a good option for the second-line, bladder-preserving standard of care for non-muscle-invasive bladder cancer unresponsive to bacillus Calmette-Guérin.

To determine whether use of neoadjuvant chemotherapy (NAC) is associated with a higher risk of post-operative complications following radical cystectomy (RC) for bladder cancer (BCa).We retrospectively reviewed records of patients undergoing RC for non-metastatic urothelial BCa at 13 tertiary care centres from 2007-2019. Patients who received NAC ('NAC + RC' group) were compared with those who underwent upfront RC ('RC alone' group) for intra-operative variables, incidence of post-operative complications as per the Clavien-Dindo classification (CDC) and rates of re-admission and re-intervention. Multivariable logistic regression analysis was performed to determine predictors of CDC overall and CDC major (grade III-V) complications. We also analysed the trend of NAC utilization over the study period.Of the 3113 patients included, 968 (31.1%) received NAC while the remaining 2145 (68.9%) underwent upfront RC for BCa. There was no significant difference between the NAC + RC and RC alone groups with regards to 30-day CDC overall (53.2% vs 54.6%, p = 0.4) and CDC major (15.5% vs 16.5%, p = 0.6) complications. The two groups were comparable for the rate of surgical re-intervention (14.6% in each group) and re-hospitalization (19.6% in NAC + RC vs 17.9% in RC alone, p = 0.2%) at 90 days. On multivariable regression analysis, NAC use was not found to be a significant predictor of 90-day CDC overall (OR 1.02, CI 0.87-1.19, p = 0.7) and CDC major (OR 1.05, CI 0.87-1.26, p = 0.6) complications. We also observed that the rate of NAC utilization increased significantly (p 0.001) from 11.1% in 2007 to 41.2% in 2019, reaching a maximum of 48.3% in 2018.This large multicentre analysis with a substantial rate of NAC utilization showed that NAC use does not lead to an increased risk of post-operative complications following RC for BCa. This calls for increasing NAC use to allow patients to avail of its proven oncologic benefit.

Objective: To evaluate the educational impact of a pilot MOOC (Massive Open Online Course), validated by the French College of Urology Teachers (FCUT), on the surgical technique of kidney transplantation.Materials and methods: We developed a MOOC on the surgical technique of kidney transplantation, based on a video of a surgical procedure, performed by an expert surgeon. The MOOC has been validated by the FCUT. We have created 2 student groups: 1) MOOC-pre-QCM group: visualization of the MOOC then answer to the MCQs and satisfaction questions; 2) MOOC-post-QCM group: answer to the MCQs then visualization of the MOOC then answers to the satisfaction questions. In total, 20 MCQs on the kidney transplantation technique were completed by the 2 groups. The answers were anonymous.Results: A total of 142 people answered the MCQs (MOOC-pre-QCM group (n=66) and MOOC-post-QCM group (n=76)). Twenty-nine percent (41/142) of the participants were fellows and 71 % (101/142) were residents. The proportion of fellows and residents was identical between the 2 groups. The rate of correct answers to the 20 MCQs was statistically higher in the MOOC-pre-QCM group, compared to the MOOC-post-QCM group (88.6 % versus 73.3 %, P, ObjectifÉvaluer l’impact pédagogique d’un MOOC (Massive Open Online Course) pilote, validé par le Collège français des enseignants en urologie (CFEU), sur la technique chirurgicale de transplantation rénale.Matériel et méthodesNous avons réalisé un MOOC sur la technique chirurgicale de transplantation rénale, à partir d’une vidéo d’une intervention chirurgicale, réalisée par un chirurgien expert. Le MOOC a été validé par le CFEU. Nous avons créé 2 groupes d’étudiants : 1) groupe MOOC-pré-QCM : visualisation du MOOC, puis réponse aux QCM et aux questions de satisfaction ; 2) groupe MOOC-post-QCM : réponse aux QCM, puis visualisation du MOOC, puis réponse aux questions de satisfaction. Au total, 20 QCM sur la technique transplantation rénale ont été remplis par les 2 groupes. Les réponses étaient anonymes.RésultatsAu total, 142 personnes ont répondu aux QCM (groupe MOOC-pré-QCM (n = 66) et groupe MOOC-post-QCM (n = 76)). 29 % (41/142) des participants étaient des CCA ou assistants et 71 % (101/142) étaient des internes. La proportion de CCA/assistants et d’internes était identique entre les 2 groupes. Le taux de réponses correctes aux 20 QCM était statistiquement supérieur dans le groupe MOOC-pré-QCM, en comparaison au groupe MOOC post-QCM (88,6 % contre 73,3 %, p < 0,0001). Au total, 91 % des étudiants ont trouvé le MOOC « Très Utile » ou « Utile ». La médiane de la note du MOOC, donnée par les étudiants, était de 8/10.ConclusionCette étude a montré un impact positif du MOOC sur les connaissances théoriques de la technique chirurgicale de transplantation rénale. Ce MOOC pourrait servir de projet pilote pour le développement d’autres MOOC sur la chirurgie urologique.Niveau3.

Periprostatic adipose tissue (PPAT) abundance correlates with prostate cancer progression, but the mechanism remains unexplained. Here, we used a statistical approach to define abundant PPAT by normalizing PPAT volume to prostate volume in a cohort of 351 patients with a linear regression model. Applying this definition, we find tumors specifically from patients with abundant PPAT exhibit several hallmarks of aggressiveness, suggesting that PPAT abundance might be used to improve risk stratification. We show that abundant PPAT expands by adipocyte hypertrophy but this does not result in inflammation. Extensive extracellular matrix remodeling, notably of the collagen network, and decreased expression of mechano-sensing proteins in adipocytes explains this inflammation-free expansion by decreasing the mechanical constraints on the adipocytes. Moreover, collagen VI degradation in abundant PPAT is associated with production of endotrophin, a matrikine that promotes cancer progression. We find high levels of endotrophin specifically in the urine of patients with abundant PPAT, indicating the clinical relevance of our findings.SummaryThe abundance of periprostatic adipose tissue favors prostate cancer aggressiveness. The increase in extracellular matrix remodeling that occurs in expanded periprostatic fat allows adipocyte hypertrophy without tissue inflammation and generates a matrikine, endotrophin, which favors tumor progression.

INTRODUCTION Artificial urinary sphincter is considered the gold standard of treatment for male urinary incontinence because of intrinsic sphincter deficiency. The objective of our study was to compare the functional results and complications of the penoscrotal and perineal incision for the implantation of artificial urinary sphincter. MATERIAL AND METHODS A retrospective, monocentric study comparing the perioperative and long-term results of primary implantation of an artificial urinary sphincter in men, performed by the penoscrotal or the perineal incision, was conducted in a French university hospital. RESULTS Between April 2004 and February 2019, 175 patients were implanted (118 by penoscrotal incision and 57 by perineal incision) by 19 surgeons. Cuff placement approach depended on surgeon preference. The average follow-up was 34.2 ± 35.6 months. Cuff size was smaller in the penoscrotal group (4 [4;5] vs 4.5[4;5] p

To describe the clinico-pathological characteristics of NMIBC treated in metropolitan France over one year when BCG was subject to a national quota. In the context of recurrent shortages of intravesical BCG for non-muscle-invasive bladder cancer (NMIBC), it is interesting to document the real-life indications for adjuvant treatment.Between February 2021 and February 2022, the French National Agency for the Safety of Medicines (ANSM) asked the French Association of Urology (AFU) to propose a science-based quota solution for BCG using a clinical score. The ANSM then asked the distributor of the drug, MEDAC, to collect the scores for all patients for whom BCG was requested by healthcare institutions and to prioritise the requests for patients with the highest scores. Tumour stage, grade, size, number, time to recurrence, carcinoma in situ, age, accessibility of alternative treatments (total cystectomy, radio-chemotherapy, thermo-chemotherapy) and BCG treatment progress (initiation or maintenance) were documented for each intravesical BCG prescription. A descriptive analysis of the data collected during the quota year was performed.During the 1-year quota, 25 878 requests for BCG were made for 19 024 patients, 60.5% of whom were ≥70-years-old. Requests for induction and maintenance treatment accounted for 12 704 (49.1%) and 13 174 (50.9%) of prescriptions, respectively. NMIBCs treated with BCG maintenance therapy were more frequently high-risk NMIBCs (91.7% vs. 90.2%, p0.0001) than NMIBCs for which induction therapy was requested. The number of cases of NMIBC leading to BCG adjuvant treatment was estimated at 12 704 cases/66 062 188 inhabitants over 1 year in metropolitan France.Our data suggest that the incidence of NMIBC at high-risk of recurrence and progression is underestimated in reference epidemiological studies. These results should help to better define future care needs.

Bladder cancer detection and follow-up is based on cystoscopy and/or cytology, but it remains imperfect and invasive. Current research focuses on diagnostic biomarkers that could improve bladder cancer detection and follow-up by discriminating patients at risk of aggressive cancer who need confirmatory TURBT (Transurethral Resection of Bladder Tumour) from patients at no risk of aggressive cancer who could be spared from useless explorations.To perform a systematic review of data on the clinical validity and clinical utility of eleven urinary biomarkers (VisioCytAll available studies on the 11 biomarkers published between May 2010 and March 2021 and present in MEDLINEMost studies on urinary biomarkers had a prospective design and high level of evidence. However, their results should be interpreted with caution given the heterogeneity among studies. Most of the biomarkers under study displayed higher detection sensitivity compared with cytology, but lower specificity. Some biomarkers may have clinical utility for NMIBC surveillance in patients with negative or equivocal cystoscopy or negative or atypical urinary cytology findings, and also for recurrence prediction.Urinary biomarkers might have a complementary place in bladder cancer diagnosis and NMIBC surveillance. However, their clinical benefit remains to be confirmed.

Upper urinary tract urothelial carcinoma (UTUC) is an uncommon disease and its gold-standard treatment is radical nephroureterectomy (RNU). Distal ureterectomy (DU) might be an alternative for tumors of the distal ureter but its indications remain unclear. Here, we aimed to evaluate the oncological outcomes of DU for UTUC of the pelvic ureter. We performed a multicenter retrospective analysis of patients with UTUC who underwent DU. The primary endpoint was 5-year cancer-specific survival (CSS), followed by overall survival (OS), intravesical recurrence-free (IVR) and homolateral urinary tract recurrence-free (HUR) survivals as secondary endpoints. Univariate and multivariate Cox regressions were performed to assess factors associated with outcomes. 155 patients were included, 91% of which were high-risk. 5-year CSS was 84.4%, OS was 71.9%, IVR-free survival was 43.6% and HUR-free survival was 74.4%. Multifocality, high grade and tumor size were the most significant predictors of survival endpoints. Of note, neither hydronephrosis nor pre-operative diagnostic ureteroscopy/JJ stent were associated with any of the endpoints. Perioperative morbidity was minimal. In conclusion, DU stands as a possible alternative to RNU for UTUC of the pelvic ureter. Close monitoring is mandatory due to the high risk of recurrence in the remaining urinary tract.

Purpose The main objective was to compare minor (Clavien I-II) and major (Clavien >= III) intra- and postoperative complications of living donor robotic assisted kidney transplantation (RAKT) in obese (>= 30 kg/m(2)BMI), overweight (< 30/ >= 25 kg/m(2)BMI) and non-overweight recipients (< 25 kg/m(2)BMI). Methods For the present retrospective study, we reviewed the multi-institutional ERUS-RAKT database to select consecutive living donor RAKT recipients. Functional outcomes, intra- and postoperative complications were compared between obese, overweight and non-overweight recipients. Results 169 living donor RAKTs were performed, by 10 surgeons, from July 2015 to September 2018 in the 8 European centers. 32 (18.9%) recipients were obese, 66 (39.1%) were overweight and 71 (42.0%) were non-overweight. Mean follow-up was 1.2 years. There were no major intra-operative complications in either study group. Conversion to open surgery occurred in 1 obese recipient, in 2 overweight recipients and no conversion occurred in non-overweight recipients (p = 0.3). Minor and major postoperative complications rates were similar in the 3 groups. At one-year of follow-up, median eGFR was similar in all groups [54 (45-60) versus 57 (46-70) versus 63 (49-78) ml/min/1.73 m(2)in obese, overweight and non-overweight recipient groups, respectively,p = 0.5]. Delayed graft function rate was similar in the 3 groups. Only the number of arteries was an independent predictive factor of suboptimal renal function at post-operative day 30 in the multivariate analysis. Conclusion RAKT in obese recipients is safe, compared to non-overweight recipients and yields very good function, when it performed at high-volume referral centers by highly trained transplant teams.

International audience; Bladder cancer is the 10th most common cancer in the world and has a high risk of recurrence and metastasis. In order to sustain high energetic needs, cancer cells undergo complex metabolic adaptations, such as a switch toward aerobic glycolysis, that can be exploited therapeutically. Reactive oxygen species (ROS) act as key regulators of cancer metabolic reprogramming and tumorigenesis, but the sources of ROS remain unidentified. Monoamine oxidases (MAOs) are mitochondrial enzymes that generate H 2 O 2 during the breakdown of catecholamines and serotonin. These enzymes are particularly important in neurological disorders, but recently, a new link between MAOs and cancer has been uncovered, involving their production of ROS. At present, the putative role of MAOs in bladder cancer has never been evaluated. We observed that human urothelial tumor explants and the bladder cancer cell line AY27 expressed both MAO-A and MAO-B isoforms. Selective inhibition of MAO-A or MAO-B limited mitochondrial ROS accumulation, cell cycle progression and proliferation of bladder cancer cells, while only MAO-A inhibition prevented cell motility. To test whether ROS contributed to MAO-induced tumorigenesis, we used a mutated form of MAO-A which was unable to produce H 2 O 2. Adenoviral transduction of the WT MAO-A stimulated the proliferation and migration of AY27 cells while the Lys305Met MAO-A mutant was inactive. This was consistent with the fact that the antioxidant Trolox strongly impaired proliferation and cell cycle progression. Most interestingly, AY27 cells were highly dependent on glucose metabolism to sustain their growth, and MAO inhibitors potently reduced glycolysis and oxidative phosphorylation, due to pyruvate depletion. Accordingly, MAO inhibitors decreased the expression of proteins involved in glucose transport (GLUT1) and transformation (HK2). In conclusion, urothelial cancer cells are characterized by a metabolic shift toward glucose-dependent metabolism, which is important for cell growth and is under the regulation of MAO-dependent oxidative stress.

Summary Background Standard treatment for high-risk non-muscle-invasive bladder cancer is transurethral resection of bladder tumour followed by intravesical BCG immunotherapy. However, despite high initial responses rates, up to 50% of patients have recurrence or become BCG-unresponsive. PD-1 pathway activation is implicated in BCG resistance. In the KEYNOTE-057 study, we evaluated pembrolizumab, a PD-1 inhibitor, in BCG-unresponsive non-muscle-invasive bladder cancer. Methods We did this open-label, single-arm, multicentre, phase 2 study in 54 sites (hospitals and cancer centres) in 14 countries. In cohort A of the trial, adults aged 18 years or older with histologically confirmed BCG-unresponsive carcinoma in situ of the bladder, with or without papillary tumours, with an Eastern Cooperative Oncology Group performance status of 0–2, and who were ineligible for or declined radical cystectomy were enrolled. All enrolled patients were assigned to receive pembrolizumab 200 mg intravenously every 3 weeks for up to 24 months or until centrally confirmed disease persistence, recurrence, or progression; unacceptable toxic effects; or withdrawal of consent. The primary endpoint was clinical complete response rate (absence of high-risk non-muscle-invasive bladder cancer or progressive disease), assessed by cystoscopy and urine cytology approximately 3 months after the first dose of study drug. Patient follow-ups were done every 3 months for the first 2 years and every 6 months thereafter for up to 5 years. Efficacy was assessed in all patients who received at least one dose of the study drug and met BCG-unresponsive criteria. Safety was assessed in all patients who received at least one dose of the study drug. This trial is registered with ClinicalTrials.gov number, NCT02625961 , and is ongoing. Findings Between Dec 9, 2015, and April 1, 2018, we screened 334 patients for inclusion. 186 patients did not meet inclusion criteria, and 47 patients were assigned to cohort B (patients with BCG-unresponsive high grade Ta or any grade T1 papillary disease without carcinoma in situ; results will be reported separately). 101 eligible patients were enrolled and assigned to receive pembrolizumab. All 101 patients received at least one dose of the study drug and were included in the safety analysis. Five patients had disease that did not meet the US Food and Drug Administration definition of BCG-unresponsive non-muscle-invasive bladder cancer and were therefore not included in the efficacy analysis (n=96). Median follow-up was 36·4 months (IQR 32·0–40·7). 39 (41%; 95% CI 30·7–51·1) of 96 patients with BCG-unresponsive carcinoma in situ of the bladder with or without papillary tumours had a complete response at 3 months. Grade 3 or 4 treatment-related adverse events occurred in 13 (13%) patients; the most common were arthralgia (in two [2%] patients) and hyponatraemia (in three [3%] patients). Serious treatment-related adverse events occurred in eight (8%) patients. There were no deaths that were considered treatment related. Interpretation Pembrolizumab monotherapy was tolerable and showed promising antitumour activity in patients with BCG-unresponsive non-muscle-invasive bladder cancer who declined or were ineligible for radical cystectomy and should be considered a a clinically active non-surgical treatment option in this difficult-to-treat population. Funding Merck Sharp & Dohme.

Recently, the use of targeted biopsy has been subject to critics, as it has been speculated that targeted biopsy might lead to overdiagnosis of clinically significant prostate cancer (PCa). In this study, we tried to evaluate whether targeted sampling in patients with organ-confined disease and ISUP 2 disease was associated with downgrading of the prostatectomy specimen, hence, leading to an unnecessary treatment, in terms of radical surgery. We relied on a prospectively-maintained multi-institutional database and identified 1293 patients with ISUP 2 disease on targeted biopsy only. Median (IQR) patients' age at diagnosis was 65 (60, 70) years. Median PSA was 6.8 (5.0, 9.6) ng/ml. Overall, only 33 (2.6%) patients presented downgrading on their RP specimens. Patients who experienced downgrading were biopsied more frequently trans-rectally, had a lower total tumor length in mm and lower percentage of maximum core involvement and lower rates of cancer on systematic biopsy (all p ≤ 0.03). The strongest factors associated with reduced risk of downgrading were total tumor length, in mm, (OR: 0.71, 95% CI: 0.62,0.82, p 0.001) and transperineal biopsy route (OR: 0.38, 95% CI: 0.14,1.00, p = 0.05).

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.

Resume Introduction L’objectif principal etait de rapporter les resultats per-, post-operatoires et fonctionnels de la transplantation renale robot-assistee (TRRA) avec donneur vivant (DV), realisees par un chirurgien expert en chirurgie robotique urologique. L’objectif secondaire etait de comparer les resultats de la TRRA avec DV, en fonction de l’experience du chirurgien. Materiels et methodes Pour cette etude de cohorte retrospective, nous avons analyse les donnees de patients consecutifs ayant eu une TRRA avec DV, de juillet 2015 a mars 2020 et nous avons compare les resultats de la TRRA en fonction de l’experience du chirurgien (groupe 1 : 1–14e TRRA versus groupe 2 : 15–29e TRRA). Resultats Au total, 29 TRRA avec DV ont ete realisees. L’âge et l’IMC median des receveurs etaient : 57,0 (44,0–66,0) ans et 32,7 (23,5–39,6) kg/m2. La duree operatoire totale mediane et le temps de console median etaient de : 140,0 (122,5–165,0) et 120,0 (107,5–137,5) minutes. Les durees medianes d’ischemie tiede, d’anastomose arterielle, veineuse et urinaire etaient de : 35,0 (27,5–45,0), 15,0 (11,0–20,0), 12,0 (10,0–16,0), 20,0 (16,0–23,0) minutes. Au total, 2 (6,9 %) complications mineures et 5 (17,2 %) complications majeures (Clavien-Dindo ≥ III) postoperatoires sont survenues. A 2 ans de suivi, la survie du patient et du transplant etait de 100 % (n = 29) et 93,1 % (n = 27). Apres la 14e TRRA, la duree d’ischemie tiede (p = 0,01) et de l’anastomose veineuse (p = 0,004) etaient statistiquement plus courtes. Conclusion La transplantation renale robot-assistee avec donneur vivant chez les receveurs obeses, presente de bons resultats fonctionnels a moyen terme. Niveau de preuve 3.

Introduction The main purpose was to assess the failure free survival of adjustable continence therapy ACT®/proACT® after continence was obtained and to seek factors influencing it. Material and methods Retrospective, single-center survival study of peri-urethral balloons implanted between 2007 and 2014. Efficacy was defined by the wearing of 0 or 1 safety pad per day. The primary end point was time to failure estimated from a survival curve (Kaplan-Meier). Factors that could influence failure free survival were: sex, age, radiotherapy, diabetes, number of pad before surgery, number of balloon inflation, early complications, mixed urinary incontinence and previous ACT®/proACT® placement. They were analyzed in a COX regression. Results Of the 82 peri-urethral balloons placed, 41 were effective in 36 patients. The failure free survival was 50 % at 60 months. Radiotherapy, diabetes and previous peri-urethral balloon placement appeared to significantly decrease survival (P=0.031;P=0.025;P=0.029, respectively). Fifteen peri-urethral balloons were still effective at the last follow-up, one was lost to follow-up and 25 required re-intervention for loss of efficacy. The main cause of efficacy loss was system leakage. Fifty-two percent of peri-urethral balloons that became ineffective were replaced by new peri-urethral balloons and 28% by an artificial urinary sphincter. Conclusion Patients who became continent with adjustable continence therapy (ACT®/proACT®) had a 50 % new surgery probability at 5 years for a loss of efficacy. Radiotherapy seems to be the main risk factor of the efficacy loss. Level of evidence IV.

Objectives: The objective of this study was to assess the impact of complete transurethral resection of bladder tumors (TURBTs) before radical cystectomy on pathological and oncological outcomes of patients with muscle-invasive bladder cancer (MIBC) and high-risk non-MIBC. Materials and Methods: The charts of all patients who underwent radical cystectomy for bladder cancer in 2 academic departments of urology between 1996 and 2016 were retrospectively reviewed. Patients were divided into 2 groups according to the completeness of the last endoscopic resection before radical cystectomy: macroscopically complete transurethral resection (complete) or macroscopically incomplete transurethral resection (incomplete). The primary end point was the recurrence-free survival (RFS). Secondary end points included cancer-specific survival (CSS) and rates of pT0 and downstaging. Results: Out of 486 patients included for analysis, the TURBT immediately preceding radical cystectomy was considered macroscopically complete in 253 patients (52.1%) and incomplete in 233 patients (47.9%). In multivariate analysis, macroscopically complete TURBT was the strongest predictor of both pT0 disease (OR = 3.1; p = 0.02) and downstaging (OR = 7.1; p < 0.0001). After a median follow-up of 41 months, macroscopically complete TURBT was associated with better RFS (5-year RFS: 57 vs. 37%; p < 0.0001) and CSS (5-year CSS: 70.8 vs. 54.5%; p = 0.002). In multivariate analysis adjusting for multifocality, weight of endoscopic resection specimen, cT4 stage on preoperative imaging, interval between endoscopic resection and radical cystectomy, neoadjuvant chemotherapy, pT stage, and associated carcinoma in situ, macroscopically complete endoscopic resection remained the main predictor of better RFS (HR = 0.4; p = 0.0003) and the only preoperative factor associated with CSS (HR = 0.5; p = 0.01). Conclusion: A macroscopically complete TURBT immediately preceding radical cystectomy may improve pathological and oncological outcomes in patients with MIBC and high-risk MIBC.

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.

Background The prognostic role of multiparametric magnetic resonance imaging (mpMRI) and systematic biopsy in predicting biochemical recurrence (BCR) after radical prostatectomy (RP) in prostate cancer (PCa) patients has not been addressed yet. Objective To develop a risk tool predicting BCR after RP in patients diagnosed with magnetic resonance imaging (MRI)-targeted biopsy. Design, setting, and participants A total of 804 patients with a clinical suspicion of PCa and positive mpMRI diagnosed with MRI-targeted plus concomitant systematic biopsy treated with RP were identified. Outcome measurements and statistical analyses The outcome was represented by BCR defined as two prostate-specific antigen (PSA) values ≥0.2 ng/ml after surgery. Multivariable Cox regression analyses assessed the predictors of BCR. A risk tool model based on imaging and biopsy parameters was developed and validated internally. The c-index, calibration plot, and decision curve analyses were used to assess discrimination, calibration, and the net benefit associated with its use in predicting BCR at 36 mo. Results and limitations Median (interquartile range) follow-up was 28 (25–29) mo, and 89 patients experienced BCR. The 36-mo BCR-free survival rate was 89%. The maximum diameter of the index lesion and seminal vesicle invasion (SVI) at mpMRI as well as the presence of clinically significant PCa at systematic biopsy (defined as a grade group of >2) were associated with BCR (all p ≤ 0.03). A model based on PSA, Prostate Imaging Reporting and Data System score, SVI at mpMRI, diameter of the index lesion, grade group at MRI-targeted biopsy, and clinically significant PCa at systematic biopsy achieved the highest discrimination (77%) among all clinical models, as well as the European Association of Urology risk groups (62%) and the Cancer of the Prostate Risk Assessment (CAPRA) score (60%). This tool was characterized by excellent calibration at internal validation and the highest net benefit when predicting BCR for the threshold risk between 0% and 30%. Conclusions The adoption of predictive models accounting for mpMRI and MRI-targeted biopsy-derived variables and concomitant systematic biopsy would improve clinicians’ ability to identify patients at a higher risk of early recurrence after surgery. Patient summary The use of information obtained at multiparametric magnetic resonance imaging (mpMRI), and MRI-targeted and concomitant systematic biopsy would improve clinicians’ ability to identify prostate cancer patients at a higher risk of experiencing early biochemical recurrence after surgery.

Summary Objective. - To update French guidelines for the management of bladder cancer specifically non-muscle invasive (NMIBC) and muscle-invasive bladder cancers (MIBC). Methods. - A Medline search was achieved between 2018 and 2020, notably regarding diagnosis, options of treatment and follow-up of bladder cancer, to evaluate different references with levels of evidence. Results. - Diagnosis of NMIBC (Ta, T1, CIS) is based on a complete deep resection of the tumor. The use of fluorescence and a second-look indication are essential to improve initial diagnosis. Risks of both recurrence and progression can be estimated using the EORTC score. A stratification of patients into low, intermediate and high risk groups is pivotal for recommending adjuvant treatment: instillation of chemotherapy (immediate post-operative, standard schedule) or intravesical BCG (standard schedule and maintenance). Cystectomy is recommended in BCG-refractory patients. Extension evaluation of MIBC is based on contrast-enhanced pelvic-abdominal and thoracic CT-scan. Multiparametric MRI can be an alternative. Cystectomy associated with extended lymph nodes dissection is considered the gold standard for non-metastatic MIBC. It should be preceded by cisplatin-based neoadjuvant chemotherapy in eligible patients. An orthotopic bladder substitution should be proposed to both male and female patients with no contraindication and in cases of negative frozen urethral samples; otherwise transileal ureterostomy is recommended as urinary diversion. All patients should be included in an Early Recovery After Surgery (ERAS) protocol. For metastatic MIBC, first-line chemotherapy using platin is recommended (GC or MVAC), when performans status (PS 60 mL/min) allow it (only in 50% of cases). In second line treatment, immunotherapy with pembrolizumab demonstrated a significant improvement in overall survival. Conclusion. - These updated French guidelines will contribute to increase the level of urological care for the diagnosis and treatment of patients diagnosed with NMIBC and MIBC.

summary Introduction. –The purpose was to propose an update of the French guidelines from the national committee ccAFU on upper tract urothelial carcinomas (UTUC). Methods. – A systematic Medline search was performed between 2018 and 2020, as regards diagnosis, options of treatment and follow-up of UTUC, to evaluate different references with levels of evidence. Results. – The diagnosis of this rare pathology is based on CT-scan acquisition during excretion and ureteroscopy with histological biopsies. Radical nephroureterectomy (RNU) remains the gold standard for surgical treatment, nevertheless a conservative endoscopic approach can be proposed for low risk lesion: unifocal tumor, possible complete resection and low grade and absence of invasion on CT-scan. Close monitoring with endoscopic follow-up (flexible ureteroscopy) in compliant patients is therefore necessary. After RNU, bladder instillation of chemotherapy is recommended to reduce risk of bladder recurrence. A systemic chemotherapy is recommended after RNU in pT2–T4 N0–3 M0 disease. Conclusion. – These updated guidelines will contribute to increase the level of urological care for diagnosis and treatment for UTUC.

Ileal orthotopic neobladder (IONB) reconstruction is the preferred urinary diversion among selected patients who have undergone radical cystectomy (RC) for bladder cancer (BCa). There is insufficient data regarding patients’ quality of life (QoL), sexual and urinary outcomes. Our objectives were to assess QoL in a multicentre cohort study, and to identify related clinical, oncological and functional factors. Patients who underwent RC with IONB reconstruction for BCa from 2010 to 2017 at one of the three French hospitals completed the following self-reported questionnaires: European Organization for Research and Treatment of Cancer (EORTC) generic (QLQ-C30) and bladder cancer specific instruments (QLQ-BLM30). To assess urinary symptoms, patients completed the Urinary Symptom Profile questionnaire (USP) and a three-day voiding diary. Univariate and multivariate analyses were computed to identify clinical, pathological, and functional predictors of global QoL score. Seventy-three patients completed questionnaires. The median age was 64 years and 86.3% were men. The median interval between surgery and responses to questionnaires was 36 months (range 12–96). Fifty-five percent of patients presented a high global QoL (EORTC-QLQC30, median score 75). A pre-RC American Society of Anesthesiologists score > 2, active neoplasia, sexual inactivity, and stress urinary incontinence were associated with a worse QoL. After a multivariate analysis, sexual inactivity was the only independent factor related to an altered QoL. Patients with IONB reconstruction after RC have a high global QoL. Sexual activity could independently impact the global QoL, and it should be assessed pre- and post-operatively by urologists.

Over the past decade, prostate cancer (PCa) diagnosis drastically evolved from systematic biopsies (SBs) to multiparametric magnetic resonance imaging (mpMRI) and targeted biopsy (TB), which have emerged as powerful imaging tools for diagnosis, staging, and preoperative planning. MRI and TB should now be widely adopted for assessing prognosis and be incorporated into predictive models. To date, the standard intermediate risk classification (IRC) defined unfavourable and favourable disease with clinical information and overall biopsy data. Roumiguie et al have proposed a new model based on mpMRI staging and grade group on TB and validated it using radical prostatectomy (RP) pathology (Urol Oncol 2020;38:386–92). The aim of our study was to validate the accuracy of this new IRC with early oncologic outcomes and biochemical recurrence (BCR) after RP. From a prospective database of RP patients with positive prebiopsy mpMRI (Prostate Imaging-Reporting and Data System score ≥3) followed by SB in combination with TB, 454 patients with intermediate-risk PCa were included. Median follow-up was 31.5 mo. The new IRC outperformed the standard IRC in predicting BCR (p = 0.007). The area under the curve was 0.613 for the new MRI- and TB-based IRC versus 0.575 for the standard IRC. This new IRC could optimise the prediction of recurrence risk before treatment decision-making. Patient summary Outcomes after surgery confirm the accuracy of the new classification of intermediate-risk prostate cancer based on magnetic resonance imaging (MRI) staging and targeted biopsy data. We found that this new classification outperformed the standard classification in predicting biochemical recurrence of cancer for men with positive MRI findings undergoing targeted biopsies.

BACKGROUND: Complications can occur following radical nephroureterectomy (RNU) in 20–40% of patients. The Comprehensive Complication Index (CCI) is an alternative grading system to the Clavien-Dindo (CD) grading system that aggregates all complications experienced by a patient on a continuous (as opposed to categorical) scale. We investigate whether the cumulative nature of CCI renders it superior to CD in predicting perioperative course after RNU. METHODS: The records of 596 patents who underwent RNU at 7 academic medical centers from 2005 to 2015 were reviewed. Complications occurring within 30 days of RNU were annotated using both the CD and CCI classification systems. Logistic regression was used to determine associations between CD and CCI with perioperative covariates as well as measures of convalescence [hospital length of stay (LOS) and readmission]. RESULTS: A total of 377 men and 219 women with a median age of 71, BMI of 27, and Charlson comorbidity score of 4 were included. Over half underwent a minimally invasive RNU. Median LOS following RNU was 6.0 days (range, 1–37 days) and readmission within 30-days occurred in 45 (8%) patients. Overall, 136 patients (23%) experienced a post-operative complication with 91 having a single complication and 45 with multiple (range, 2–6); 44 (7%) patients had Clavien III or greater complications, and the median CCI for those patients experiencing a complication was 20.9 (range, 8.7–100). Both the upper quartile of CCI (≥75th %) and major CD complications were associated with higher baseline Charlson score, ECOG ≥2, and CKD stage ≥ III (all P

To compare perioperative and functional outcomes of two different energy sources, holmium laser and bipolar current for endoscopic enucleation of prostate larger than 60 mL. A prospective, monocentric, comparative, non-randomized study was conducted including all patients treated for prostate larger than 60 mL, measured by transrectal ultrasound. Patients were assigned to each group based on the surgeons' practice. Perioperative data were collected (preoperative characteristics, operating, catheterization and hospitalization times, hemoglobin loss, complications) and functional outcomes (IPSS, IPSS Quality of Life (QoL), PSA) at 3 months and 1 year. 100 patients were included in each group from October 2015 to March 2018. No differences between HoLEP and plasma groups were observed at baseline, except for mean IPSS score, IPSS QoL score and preoperative PVR that were significantly higher in the HoLEP group. Operating time (142.1 vs 122.4 min; p = 0.01), catheterization time (59.6 vs 44.4 h; p = 0.01) and hospitalization time (2.5 vs 1.8 days; p = 0.02) were significantly shorter in the plasma group. Complication and transfusion rate were no significantly different between HoLEP and plasma. No significant differences were observed concerning functional outcomes at 3 months and 1 year. The urinary incontinence rate was higher 21.1% vs 6.4% (p

Introduction Treatment decision-making for intermediate-risk prostate cancer (CaP) is mainly based on grade and tumor involvement on systematic biopsy. We aimed to assess the added value of multi-parametric magnetic resonance imaging (mpMRI) and targeted biopsy (TB) features for predicting final pathology and for improving the well-established favourable/unfavourable systematic biopsy-based sub-classification. Materials and Methods From a prospective database of 377 intermediate risk CaP cases, we evaluated the performance of the standard intermediate risk classification (IRC), and the predictive factors for unfavourable disease on final pathology aiming to build a new model. Overall unfavourable disease (OUD) was defined by any pT3-4 and/or pN1 and/or grade group (GG) ≥ 3. Results The standard IRC was found to be predictive for unfavourable disease in this population. However, in multivariable analysis regression, ECE on mpMRI and GG ≥3 on TB remained the 2 independent predictive factors for OUD disease (HR = 2.7, P = 0.032, and HR = 2.41, P = 0.01, respectively). By using the new IRC in which unfavorable risk was defined by ECE on mpMRI and/or GG ≥3 on TB, the proportion of unfavorable cases decreased from 62.3% to 34.1% while better predicting unfavorable disease in RP speciments. The new model displayed a better accuracy than the standard IRC for predicting OUD (AUC: 0.66 vs. 0.55). Conclusions The integration of imaging and TB features drastically improves the intermediate risk sub-classification performance and better discriminates the unfavourable risk group that could benefit from more aggressive therapy such as neo-adjuvant and/or adjuvant treatment, and the favourable group that could avoid over-treatment. External validation in other datasets is needed.

OBJECTIVE To assess the impact of concomitant targeted biopsies (TB) for predicting final disease reclassification in MRI-positive low-risk prostate cancer patients eligible for active surveillance (AS) on systematic biopsies (SB). MATERIALS AND METHODS From a prospective database, we included all prebiopsy MRI-positive men fulfilling AS criteria at diagnosis (Toronto [n = 114], UCSF [n = 82], or PRIAS [n = 60] criteria) on SB. All patients underwent a combination of SB and software-based fusion TB, and an immediate radical prostatectomy. The primary endpoints were the pathologic upgrading and upstaging rates. RESULTS Biopsy grade group was upgraded to grade group (GG) 2 and to GG≥3 on TB in 65.9%-76.7% and in 12.2-16.7%, respectively. The rate of GG ≥3 in radical prostatectomy specimens varied from 31.6% to 43.3% with no relation between strictest criteria and lower upgrading rates. The proportion of not organ-confined disease (35%-39%) was comparable among the AS cohorts. Negative TB was strongly associated with the absence of final GG ≥3. Tumor grade on TB was significantly correlated with the risk of final GG ≥3 in both Toronto and UCSF cohorts, not in the PRIAS cohort. In the PRIAS cohort, the only independent predictive factor for GG ≥3 disease was the maximal tumor length in any core (P = .034). CONCLUSION In MRI-positive patients, the risk of disease reclassification was comparable whatever the SB-based AS criteria used. TB were predictive of final upgrading, with a varied impact according to the AS criteria. SB features remained relevant for reclassification prediction even in case of positive TB. The risk of upstaged disease remains important, approximately one third, and neither TB/SB parameters nor MRI findings could accurately predict it.

Prostate is surrounded by a specific fat depot called periprostatic adipose tissue (PPAT) that contributes through paracrine mechanisms to prostate cancer (PCa) progression. Like other white adipose tissues, PPAT stores lipids and is an endocrine organ. However, PPAT is still poorly characterized. Nevertheless, current evidence highlights that soluble factors secreted from PPAT might promote PCa aggressiveness and local dissemination. In addition, the ability of adipocytes to provide lipids to tumor cells participates in tumor aggressiveness. The secretory and metabolic profile of PPAT is modified by obesity, a state associated with greater occurrences of aggressive diseases. Beyond obesity, the excessive accumulation of PPAT, independently of the ponderal status of the patients, is an emerging risk factor in aggressive diseases. Characterization of the role of human PPAT on PCa progression will undoubtedly provide, in the near future, new therapeutic strategies and new risk stratification factors in PCa.

A trend towards greater benefit from adjuvant chemotherapy (ACT) in pN+ bladder cancer (BCa) has been observed in multiple randomized controlled trials. However, it is still unclear which patients might benefit the most from this approach. We retrospectively analyzed a multicenter cohort of 1381 patients with pTany pN1-3 cM0 R0 urothelial BCa treated with radical cystectomy (RC) with or without cisplatin-based ACT. The main endpoint was overall survival (OS) after RC. We performed 1:1 propensity score matching to adjust for baseline characteristics and conducted a classification and regression tree (CART) analysis to assess postoperative risk groups and Cox regression analyses to predict OS. Overall, 391 patients (28%) received cisplatin-based ACT. After matching, two cohorts of 281 patients with pN+ BCa were obtained. CART analysis stratified patients into three risk groups: favorable prognosis (≤pT2 and positive lymph node [PLN] count ≤2; odds ratio [OR] 0.43), intermediate prognosis (≥pT3 and PLN count ≤2; OR 0.92), and poor prognosis (pTany and PLN count ≥3; OR 1.36). Only patients with poor prognosis benefitted from ACT in terms of OS (HR 0.51; p 0.001). We created the first algorithm that stratifies patients with pN+ BCa into prognostic classes and identified patients with pTany BCa with PLN ≥3 as the most suitable candidates for cisplatin-based ACT. PATIENT SUMMARY: We found that overall survival among patients with bladder cancer and evidence of lymph node involvement depends on cancer stage and the number of positive lymph nodes. Patients with more than three nodes affected by metastases seem to experience the greatest overall survival benefit from cisplatin-based chemotherapy after bladder removal. Our study suggests that patients with the highest risk should be prioritized for cisplatin-based chemotherapy after bladder removal.

Background Despite the key importance of magnetic resonance imaging (MRI) parameters, risk classification systems for biochemical recurrence (BCR) in prostate cancer (PCa) patients treated with radical prostatectomy (RP) are still based on clinical variables alone. Objective We aimed at developing and validating a novel classification integrating clinical and radiological parameters. Design, setting, and participants A retrospective multicenter cohort study was conducted between 2014 and 2020 across seven academic international referral centers. A total of 2565 patients treated with RP for PCa were identified. Outcome measurements and statistical analysis Early BCR was defined as two prostate-specific antigen (PSA) values of ≥0.2 ng/ml within 3 yr after RP. Kaplan-Meier and Cox regressions tested time and predictors of BCR. Development and validation cohorts were generated from the overall patient sample. A model predicting early BCR based on Cox-derived coefficients represented the basis for a nomogram that was validated externally. Predictors consisted of PSA, biopsy grade group, MRI stage, and the maximum diameter of lesion at MRI. Novel risk categories were then identified. The Harrel’s concordance index (c-index) compared the accuracy of our risk stratification with the European Association of Urology (EAU), Cancer of the Prostate Risk Assessment (CAPRA), and International Staging Collaboration for Cancer of the Prostate (STAR-CAP) risk groups in predicting early BCR. Results and limitations Overall, 200 (8%), 1834 (71%), and 531 (21%) had low-, intermediate-, and high-risk disease according to the EAU risk groups. The 3-yr overall BCR-free survival rate was 84%. No differences were observed in the 3-yr BCR-free survival between EAU low- and intermediate-risk groups (88% vs 87%; p = 0.1). The novel nomogram depicted optimal discrimination at external validation (c-index 78%). Four new risk categories were identified based on the predictors included in the Cox-based nomogram. This new risk classification had higher accuracy in predicting early BCR (c-index 70%) than the EAU, CAPRA, and STAR-CAP risk classifications (c-index 64%, 63%, and 67%, respectively). Conclusions We developed and externally validated four novel categories based on clinical and radiological parameters to predict early BCR. This novel classification exhibited higher accuracy than the available tools. Patient summary Our novel and straightforward risk classification outperformed currently available preoperative risk tools and should, therefore, assist physicians in preoperative counseling of men candidate to radical treatment for prostate cancer.

International audience; White adipose tissue accumulates at various sites throughout the body and some adipose tissue depots exist in close proximity to organs, whose function they could influence in a paracrine manner. Prostate gland is surrounded by a poorly characterized adipose depot called periprostatic adipose tissue (PPAT) playing emerging roles in prostate-related disorders. Unlike all other adipose depots, PPAT secretes pro-inflammatory cytokines even in lean individuals and does not increase in volume during obesity. These unique features remain unexplained due to the poor structural and functional characterization of this tissue. We characterized the structural organization of PPAT in patients in comparison to abdominopelvic adipose tissue (APAT), an extraperitoneal adipose depot whose accumulation is correlated to BMI. Confocal microscopy followed by 3D reconstructions showed a sparse vascular network in PPAT when compared with that in APAT, suggesting that this tissue is hypoxic. Unbiased comparisons of PPAT and APAT transcriptomes found that most differentially expressed genes were related to the hypoxia response. High levels of the hypoxia-inducible factor HIF-2α confirmed the presence of an adaptive response to hypoxia in PPAT. This chronic hypoxic state was associated with inflammation and fibrosis, which were not further upregulated by obesity. This fibrosis and inflammation explain the failure of PPAT to expand in obesity and open new mechanistic avenues to explain its role in prostate-related disorders including cancer

Background: Robotic-assisted radical cystectomy (RARC) with intracorporeal urinary diversion (ICUD) is surging worldwide. Aim of the study was to perform a multicentric cost-analysis of RARC by comparing the gross cost of the intervention across hospitals in four different European countries. Methods: Patients who underwent RARC + ICUD were recruited from eleven European centers in four European countries (Belgium, France, Netherlands, and UK) between 2015 and 2020. Costs were divided into six parts: cost for hospital stay, cost for ICU stay, cost for surgical theater occupation, cost for transfusion, cost for robotic instruments, and cost for stapling instruments. These costs were individually assessed for each patient. Results: A total of 490 patients were included. Median operative time was 300(270–360) minutes and median hospital length-of-stay was 11(8–15) days. The average total cost of RARC was 14.794€ (95%CI 14.300–15.200€). A significant difference was found for the total cost, as well as the various subcosts abovementioned, between the four included countries. Different sets and types of robotic instruments were used by each center, leading to a difference in cost of robotic instrumentation. Nearly 84% of costs of RARC were due to hospital stay (42%), ICU stay (3%) and operative time (39%), while 16% of costs were due to robotic (8%) and stapling (8%) instruments. Conclusion: Costs and subcosts of RARC + ICUD vary significantly across European countries and are mainly dependent of hospital length-of-stay and operative time rather than robotic instrumentation. Decreasing length-of-stay and reducing operative time could help to decrease the cost of RARC and make it more widely accessible.

LBA442 Background: Although most pts with HR NMIBC respond to BCG, pts whose cancer does not respond or who relapse within 12 mo have poor prognosis and require radical cystectomy (RC). The single-arm, multicohort phase 2 KEYNOTE-057 trial (NCT02625961) was designed to investigate the safety and efficacy of pembro monotherapy for pts with BCG-unresponsive HR NMIBC (per FDA) who were ineligible or declined to undergo RC. Results from cohort A (carcinoma in situ [CIS] ± papillary tumors) showed a clinical complete response rate of 41% at 3 mo and led to approval of pembro monotherapy for such pts in the United States. We describe the results from cohort B (papillary tumors without CIS). Methods: Pts were aged ≥18 y with BCG-unresponsive HR NMIBC with papillary tumors only (high-grade Ta or any-grade T1) at baseline and ECOG PS 0-2. Pts received pembro 200 mg every 3 wk (Q3W) for ≤35 cycles (~2 y). Cancer was assessed at 12 wk and Q12W thereafter if no recurrent HR NMIBC or progression was observed; CT urography was done Q24W. Primary end points for cohort B were 12-mo disease-free survival (DFS) rate of HR NMIBC as assessed by central pathology/radiology review and safety, assuming a 12-mo DFS of >20% for HR NMIBC. Secondary efficacy end points were 12-mo DFS rate of any disease; progression-free survival (PFS) to worsening of grade, stage, or death; PFS to muscle invasion, metastasis, or death; and overall survival (OS). Results: Overall, 132 pts received pembro for a median of 9.5 cycles (range, 1.0-35.0). Median age was 72 y (range, 37-87); 57 pts (43.2%) had T1 stage; all pts (100%) had urothelial histology; 104 pts (78.8%) were male; pts received a median of 10 (range, 6-33) prior BCG instillations. Median follow-up was 45.4 mo (range, 14.9-77.1). Efficacy data are shown in Table. Thirty-one pts (23.5%) had RC after stopping pembro. Treatment-related AEs occurred in 97 pts (73.5%); 19 (14.4%) had a grade 3/4 treatment-related AE and 14 pts (10.6%) discontinued due to a treatment-related AE. No deaths from treatment-related AEs occurred. Conclusions: Pembro showed notable antitumor activity in pts with BCG-unresponsive non-CIS papillary HR NMIBC after ~45 mo of follow-up. Toxicity was manageable and consistent with that in cohort A, with no new safety signals. Results suggest pts with non-CIS papillary HR NMIBC unresponsive to BCG who declined or were ineligible to undergo RC may also benefit from pembro monotherapy. Clinical trial information: NCT02625961 . [Table: see text]