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Objectives: To describe the clinico‐pathological characteristics of non‐muscle‐invasive bladder cancer (NMIBC) treated in metropolitan France over 1 year when bacille Calmette‐Guérin (BCG) was subject to a national quota, and to document, in the context of recurrent shortages of intravesical BCG for NMIBC, the real‐life indications for adjuvant treatment. Materials and Methods: Between February 2021 and February 2022, the French National Agency for the Safety of Medicines (ANSM) asked the French Association of Urology 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 prioritize 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. Results: During the 1‐year quota, 25 878 requests for BCG were made for 19 024 patients, 60.5% of whom were aged ≥70 years. Requests for induction and maintenance treatment accounted for 12 704 (49.1%) and 13 174 prescriptions (50.9%), respectively. NMIBC treated with BCG maintenance therapy was more frequently high‐risk NMIBC (91.7% vs 90.2%; P < 0.0001) than NMIBC 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. Conclusions: 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. [ABSTRACT FROM AUTHOR]

Background: 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. Objective: To perform a systematic review of data on the clinical validity and clinical utility of eleven urinary biomarkers (VisioCyt®, Xpert®Bladder, BTA stat®, BTA TRAK™, NMP22 BC®, NMP22® BladderChek® Test, ImmunoCyt™/uCyt1+™, UroVysion Bladder Cancer Kit®, Cxbladder, ADXBLADDER, Urodiag®) for bladder cancer diagnosis and for non-muscle invasive bladder cancer (NMIBC) follow-up. Methods: All available studies on the 11 biomarkers published between May 2010 and March 2021 and present in MEDLINE® were reviewed. The main endpoints were clinical performance for bladder cancer detection, recurrence or progression during NMIBC monitoring, and additional value compared to cytology and/or cystoscopy. Results: Most 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. Conclusion: Urinary biomarkers might have a complementary place in bladder cancer diagnosis and NMIBC surveillance. However, their clinical benefit remains to be confirmed. [ABSTRACT FROM AUTHOR]

Purpose: PSA is known to be lowered in obese patients. There is a lack of data regarding patients with prostate cancer. Our objective was to prospectively assess the relationship PSA concentration, PSA mass and BMI in a cohort of patients with localized prostate cancer. Methods: A prospective, multicenter cohort study was conducted including patients undergoing radical prostatectomy. Clinical and biological data were collected for each patient before surgery. Results: A total of 1343 patients were analyzed. Mean age was 64.0 years. Mean weight was 82.2 kg and mean BMI was 26.8 kg/m2. Mean PSA concentration was 8.7 ng/mL and mean PSA mass 29.3 ng. On univariate analysis, an association was found between PSA mass and either BMI, weight and waist circumference. No association was found between PSA concentration and each weight parameters. On multivariate analysis, obesity was not an independent predictor of PSA concentration (p = 0.73). Independent predictors of PSA concentration were cardiovascular disease (negative association, p = 0.034), predominant Gleason 4 (positive association, p < 0.001) and pT3a (positive association, p < 0.001). BMI was an independent predictor of PSA mass (positive association, p = 0.009). PSA mass was negatively associated with TT (p = 0.015) and cardiovascular disease (p = 0.003), and positively associated with BT (p = 0.032), Gleason grade ≥ 4 + 3 (p < 0.001) and pT3a (p < 0.001). Conclusion: In this prospective study of patients with localized prostate cancer, higher BMI was associated with higher PSA mass but not with higher PSA concentration. Screening obese patients with a specific PSA method does not appear to be critical. [ABSTRACT FROM AUTHOR]

Background: We aim to correlate multiparametric magnetic resonance imaging (mpMRI) of the prostate reporting (Prostate Imaging Reporting and Data System [PI-RADS] version 2) with the Gleason score into both radical prostatectomy (RP) specimen and MRI fusion-targeted biopsies (FTB). Methods: mpMRI of 74 patients who underwent an RP after FTB were retrospectively reviewed. The Gleason score distribution was compared according to the PI-RADS score using the Kruskal-Wallis test. Results were compared to those of the mpMRI-guided biopsy of the same anatomical zone. For comparison, 903 RP specimen and their corresponding classical biopsies were also reviewed. Cohen's kappa concordance test was used to compare biopsies and prostatectomy specimen analyses. Results: An exact match between Gleason grade in RP specimen and FTB was found in 62% of the cases. There was no significant difference in Gleason score ≤ 7 (3 + 4) vs. ≥ 7 (4 + 3) distribution according to the PI-RADS scores (p = 0.096). Overall, Kappa coefficients were similar with MRI-targeted biopsies compared to classical biopsies (k = 0.378, 95% CI [0.194-0.563], and k = 0.316, 95% CI [0.259-0.374], respectively). Conclusions: PI-RADS score was not associated with significant differences regarding Gleason score distribution within target. Moreover, concordance of Gleason score in both MRI-targeted and classical biopsies with those within target in RP specimen was weak. [ABSTRACT FROM AUTHOR]

Context Pelvic organ-preserving radical cystectomy ( POPRC) for women may improve postoperative sexual and urinary functions without compromising the oncological outcome compared with standard radical cystectomy ( RC). Objective To determine the effect of POPRC on sexual, oncological and urinary outcomes compared with RC in women who undergo standard curative surgery and orthotopic neobladder substitution for bladder cancer. Evidence acquisition Medline, Embase, Cochrane controlled trials databases and clinicaltrial.gov were systematically searched for all relevant publications. Women with bladder cancer who underwent POPRC or standard RC and orthotopic neobladder substitution with curative intent were included. Prospective and retrospective comparative studies and single-arm case series were included. The primary outcomes were sexual function at 6-12 months after surgery and oncological outcomes including disease recurrence and overall survival ( OS) at >2 years. Secondary outcomes included urinary continence at 6-12 months. Risk of bias (RoB) assessment was performed using standard Cochrane review methodology including additional domains based on confounder assessment. Evidence synthesis The searches yielded 11 941 discrete articles, of which 15 articles reporting on 15 studies recruiting a total of 874 patients were eligible for inclusion. Three papers had a matched-pair study design and the rest of the studies were mainly small, retrospective case series. Sexual outcomes were reported in seven studies with 167/194 patients (86%) having resumed sexual activity within 6 months postoperatively, with median (range) patients' sexual satisfaction score of 88.5 (80-100)%. Survival outcomes were reported in seven studies on 197 patients, with a mean follow-up of between 12 and 132 months. At 3 and 5 years, cancer-specific survival was 70-100% and OS was 65-100%. In all, 11 studies reported continence outcomes. Overall, the daytime and night-time continence rates were 58-100% and 42-100%, respectively. Overall, the self-catheterisation rate was 9.5-78%. Due to poor reporting and large heterogeneity between studies, instead of subgroup-analysis, a narrative synthesis approach was used. The overall RoB was high across all studies. Conclusion For well-selected patients, POPRC with orthotopic neobladder may potentially be comparable to standard RC for oncological outcomes, whilst improving sexual and urinary function outcomes. However, in women undergoing RC, oncological and functional data regarding POPRC remain immature and require further evaluation in a prospective comparative setting. [ABSTRACT FROM AUTHOR]

Purpose: Positive surgical margins (PSMs) after radical prostatectomy (RP) are a known factor associated with biochemical recurrence (BCR) and raise the issue of adjuvant treatment by radiotherapy versus salvage treatment at recurrence. To help this choice, our study aimed to analyze BCR-free survival and factors associated with BCR in patients with PSM and undetectable postoperative prostate-specific antigen (PSA). Methods: Between 2005 and 2008, 630 patients had RP for localized prostate cancer in our center. We included patients with PSM, uninvaded nods, undetectable postoperative PSA and no adjuvant treatment. The 5-year BCR-free survival was calculated using Kaplan-Meier method. Logistic regression models were used to determine the factors associated with BCR in univariate and multivariate analyses (Cox model). Results: The PSM rate was 32.7 % ( n = 206 patients), and 110 patients corresponded to the inclusion criteria. The median follow-up was 72 months. The BCR rate was 30 % with a 5-year BCR-free survival of 83.9 %. The factors significantly associated with BCR were preoperative PSA, predominance and percentage of Gleason 4, tumor volume, PSM length and predominance of Gleason 4 at the margin. In the multivariate analysis, the remaining two significant factors were PSM length [OR 4.35, 95 % CI (1.011-1.421), p = 0.037] and tumor volume [OR 4.29, 95 % CI (1.011-1.483), p = 0.038]. Conclusion: Over a 5-year follow-up, only one-third of patients experienced BCR. It might be reasonable to postpone adjuvant radiotherapy for patients with PSM and undetectable PSA after RP. Tumor volume and PSM length were associated with BCR and should be taken into account in the postoperative treatment management. [ABSTRACT FROM AUTHOR]

Purpose: To compare histological features of prostate cancer according to both obesity, defined by a body mass index (BMI) ≥30 kg/m2, and androgenic status in patients who underwent radical prostatectomy. Materials and methods: Between March 2007 and September 2013, clinical, pathological and biological data were prospectively collected for patients referred for radical prostatectomy in a single European center. Preoperative total testosterone (TT) and bioavailable testosterone (bioT) serum determinations were performed. The threshold for hypogonadism was set at TT <3 ng/mL. The preoperative PSA value was registered. Gleason score (GS) and predominant Gleason pattern (PrdGP) were determined in prostate tissue specimens, and crosschecked by two uro-pathologists. Statistical analyzes were done for PrdGP4 risk assessment. Results: A total of 937 consecutive patients were included. One hundred and thirty-five filled the criterion for obesity (14.4%), out of which 42 had TT <3 ng/mL (31.1%), while in non-obese patients, only 97 had TT <3 ng/mL (12.0%). In prostate specimens, mean GS was 6.8±0.5: 291 patients (31.1%) had a PrdGP4. The incidence of PrdGP4 was higher (p<0.001) in the 135 obese patients [50% when hypogonadal (p<0.02) or 42% when eugonadal (p<0.005)] than in non-obese patients (28.9% and 27.1%, respectively). In multivariable analyzis for PrdGP4 risk, obesity, TT <3 ng/mL, PSA, and age were independent risk factors. Conclusions: Both obesity and hypogonadism are independent risk factors for PrdGP4 in patients who underwent radical prostatectomy and should be taken into account in localized prostate cancer management, to improve the therapeutic choice, especially when prostate sparing approach is considered. [ABSTRACT FROM AUTHOR]

Objective In accordance with the European Association of Urology guidelines, a second transurethral resection of the bladder (TURB) is recommended for high-grade or T1-category tumors. This practice brings into question the benefit of photodynamic diagnosis (PDD) in reducing the residual disease after TURB in patients with positive results on urine cytology showing high-grade cancer cells. Methods and materials A prospective, bicentric, randomized study comparing white light cystoscopy (WLC)+PDD with hexaminolevulinate arm with WLC alone (control arm) during the first TURB in patients with primary non–muscle-invasive bladder cancer and with positive results on urine cytology showing high-grade cancer cells. Patients underwent a first TURB with WLC and PDD or WLC alone, and then a second TURB with WLC and PDD, after 4 to 6 weeks. The number of tumors visualized in WLC and PDD and histology of the TURB specimen was recorded to perform a statistical analysis comparing both the 2 arms. Results A total of 151 patients were enrolled (hexaminolevulinate, n = 72; control, n = 79). The number of visualized tumors did not increase with PDD in the first or second TURB. During the second TURB, the residual tumor rate was not reduced in patients who had PDD during the first TURB. No significant difference was observed regarding the pattern of category and grade, the size, and the recurrence and progression risks during either the first or the second TURB. Conclusions In the setting of primary non–muscle-invasive bladder cancer with positive results on urine cytology, performing a second TURB allows to diagnose residual tumor in approximately half of the cases. This rate was not significantly reduced by the use of the PDD during the first TURB. [ABSTRACT FROM AUTHOR]

What's known on the subject? and What does the study add? Positive surgical margin ( PSM) frequency after radical cystectomy has been estimated to be 4-15%. Studies that have not distinguished between the different sites of PSM have failed to show that they are an independent prognostic factor for disease-free survival. Only perivesical soft tissue PSMs have been associated with an increased risk of cancer recurrence and cancer-specific death., This is the first comprehensive published analysis of PSMs occurring during radical cystectomy for pTx pN0 M0 bladder cancer according to their location, comparing their cancer-specific survival ( CSS) and other outcomes with those of a control group paired according to TNM status, age, sex and urinary diversion method. Local recurrence-free survival rates were found to be lower in patients with both soft tissue and urethral PSMs. Moreover, soft-tissue PSMs were associated with lower metastatic recurrence-free and CSS rates., Objective To compare the prognoses associated with positive surgical margins ( PSMs) according to their urethral, ureteric and/or soft tissue locations in patients with pN0 M0 bladder cancer who have not undergone neoadjuvant chemotherapy., Patients and Methods A retrospective, case-control study was conducted between 1991 and 2011 using data from 17 academic centres in France., A total of 154 patients (cases) with PSMs met the eligibility criteria and were matched according to centre, p T stage, gender, age and urinary diversion method with a population-based sample of 154 patients (controls) from 3651 patients who had undergone cystectomies., The median follow-up period was 23.9 months., Multivariable Cox regression analysis was used to test the effects of PSMs on local recurrence ( LR)-free survival, metastatic recurrence ( MR)-free survival and cancer-specific survival ( CSS)., Results The 5-year LR-free survival and CSS rates of patients with urethral and soft tissue PSMs were lower than those in the control group., A significant decrease in CSS was associated with soft tissue PSMs ( P = 0.003, odds ratio = 0.425, 95% confidence interval 0.283-0.647). The prognosis was not affected in cases of ureteric PSMs., Conclusions Soft tissue PSMs were associated with poor CSS rates in patients with pN0 M0 bladder cancer., A correlation between urethrectomy and a reduction of the risk of LR in a urethral PSM setting was observed. [ABSTRACT FROM AUTHOR]

Study Type - Prognosis (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Patients with end-stage renal disease (ESRD) have an increased risk of developing RCC in their native kidneys. The prevalence of RCC is 3-4% in cases of ESRD in dialyzed and/or transplanted patients, which corresponds to a rate 100-times higher than that in the general population. This is the first study, to our knowledge, comparing the characteristics of kidney cancer in the ESRD population according to their dialysis or transplantation status at the time of diagnosis. The differences in stage and survival we observed may be due to differences in surveillance strategies between transplanted and not transplanted patients, nevertheless, the differences in pathological subtypes suggest they could also be due to differences in the tumorigenesis process. OBJECTIVE To compare clinical, pathological and outcome features of renal cell carcinomas (RCCs) arising in patients with chronic renal failure (CRF) with or without renal transplantation., PATIENTS AND METHODS In all, 24 French University Departments of Urology and Kidney Transplantation participated in this retrospective study comparing RCCs arising in patients with CRF according to their dialysis or transplantation status at the time of diagnosis., Information about age, sex, symptoms, duration of CRF, mode and duration of dialysis, renal transplantation, tumour staging and grading, histological subtype and outcome were recorded in a unique database., Qualitative and quantitative variables were compared by using chi-square and Student statistical analysis. Survival was assessed by Kaplan-Meier and Cox methods., RESULTS Data on 303 RCC cases diagnosed between 1985 and 2009 were identified in 206 men (76.3%) and 64 women (23.7%)., Transplanted and not transplanted patients accounted for 213 (70.3%) and 90 cases (29.7%), respectively., In transplant recipients, RCC was diagnosed at a younger age [mean ( sd) 53 (11) vs 61 (14) years, P < 0.001), the mean tumour size was smaller [3.4 (2.3) vs 4.2 (3.1) cm, P= 0.02), pT1a stage (75 vs 60%, P= 0.009) and papillary histological subtype (44 vs 22%, P < 0.001) were more frequent than in their dialysis-only counterparts., Nodal (1 vs 6%, P= 0.03) and distant metastases rates (0 vs 5%, P < 0.001) were significantly increased in patients who had not had a transplant. However, Fürhman grading, symptoms, tumour multifocality or bilaterality, presence of acquired cystic kidney disease, were not significantly different between the groups., Estimated 5-year survival rates were 97% and 77% for transplanted and not transplanted patients, respectively ( P < 0.001). In univariate analysis, presence of symptoms ( P= 0.008), poor performance status ( P= 0.04), large tumour size, advanced TNM stage ( P < 0.001), high Führman grade ( P= 0.005) and absence of transplantation ( P < 0.001) were all adverse prognostic factors. In multivariate analysis, only T stage remained an independent predictor for cancer-related death ( P < 0.001)., CONCLUSION RCC arising in native kidneys of transplant patients seems to exhibit many favourable clinical, pathological and outcome features compared with those diagnosed in dialysis-only patients. Further research is needed to determine whether it is due to particular molecular pathways or to biases in relation to mode of diagnosis. [ABSTRACT FROM AUTHOR]

Purpose: To describe the epidemiology, clinical features, and prognostic factors of local recurrence (LR) in a large case series of patients treated by radical cystectomy (RC) for bladder cancer. Methods: A retrospective study was conducted on 903 patients treated in a single tertiary reference center. All cases of LR were identified. Descriptive analysis was performed on the clinical features, evolution, and overall mortality of these patients. Prognostic factors of LR were assessed using the Mann-Whitney test for continuous variables and the χ test for categorical variables. Results: Fifty-three patients were diagnosed with LR during follow-up (5.9 %). One patient had concomitant distant metastasis. Pain was the most frequent symptom leading to diagnosis. Mean time interval from RC to LR was 14.4 ± 13 months (1-64) with 50 % of cases diagnosed in the first postoperative year. Overall median survival of patients diagnosed with LR was 9 months [95 % confidence interval (6-11)]. Advanced pathological stage (T3 or T4) and lymph-node invasion were associated with increased LR rate in univariate and multivariate analysis. Presence of squamous cell carcinoma (SCC) was associated with a poorer prognosis after LR compared to pure urothelial carcinoma ( p = 0.04). None of the parameters tested was associated with time interval between RC and LR diagnosis. Conclusions: LR is not uncommon, favored by high pathological stage (T3/T4), and has a very bad prognosis, particularly when SCC is present. LR must be carefully tracked during follow-up after RC, and optimal management of these cases remains to be determined. [ABSTRACT FROM AUTHOR]

TP53 and FGFR3 mutations are the most common mutations in bladder cancers. FGFR3 mutations are most frequent in low-grade low-stage tumours, whereas TP53 mutations are most frequent in high-grade high-stage tumours. Several studies have reported FGFR3 and TP53 mutations to be mutually exclusive events, whereas others have reported them to be independent. We carried out a meta-analysis of published findings for FGFR3 and TP53 mutations in bladder cancer (535 tumours, 6 publications) and additional unpublished data for 382 tumours. TP53 and FGFR3 mutations were not independent events for all tumours considered together (OR = 0.25 [0.18-0.37], p = 0.0001) or for pT1 tumours alone (OR = 0.47 [0.28-0.79], p = 0.0009). However, if the analysis was restricted to pTa tumours or to muscle-invasive tumours alone, FGFR3 and TP53 mutations were independent events (OR = 0.56 [0.23-1.36] (p = 0.12) and OR = 0.99 [0.37-2.7] (p = 0.35), respectively). After stratification of the tumours by stage and grade, no dependence was detected in the five tumour groups considered (pTaG1 and pTaG2 together, pTaG3, pT1G2, pT1G3, pT2-4). These differences in findings can be attributed to the putative existence of two different pathways of tumour progression in bladder cancer: the CIS pathway, in which FGFR3 mutations are rare, and the Ta pathway, in which FGFR3 mutations are frequent. TP53 mutations occur at the earliest stage of the CIS pathway, whereas they occur would much later in the Ta pathway, at the T1G3 or muscle-invasive stage. [ABSTRACT FROM AUTHOR]

Study Type - Therapy (retrospective cohort) Level of Evidence 2b What's known on the subject? and What does the study add? The more that bladder cancer progresses from the urothelium to the outside of the bladder the worse the prognosis. To date, the use of adjuvant chemotherapy has not been completely defined. The present study clarifies the prognosis and benefits of adjuvant chemotherapy for different stages of bladder cancer that invade perivesical fat. OBJECTIVE To assess the prognosis of pT2b, pT3a and pT3b bladder cancers after radical cystectomy (RC) in order to define potential situations where chemotherapy may be of benefit., PATIENTS AND METHODS Between 1985 and 2009, 903 patients underwent a RC and pelvic bilateral lymphadenectomy in an Institutional Referral Centre., In all, 87 patients (9.6%) had a pT2b tumour, 111 patients (12.3%) a pT3a tumour, and 129 patients (14.3%) a pT3b tumour., The median (range) overall follow-up was 23 (1-350) months., Overall (OS), disease-specific (DSS), metastases-free (MFS) and local recurrence-free survival (LRFS) was estimated and compared using Kaplan-Meier plots and log-rank test., RESULTS The 5-year survivals pT2b and pT3a were similar for LRFS (86% vs 84%), MFS (69% vs 63%), DSS (72% vs 70%) and OS (66% vs 61%), and the prognosis was better than for pT3b stage tumours (69%, 44%, 40%, and 31% respectively)., In pN0 disease, MFS differences between pT2b-pT3a and pT3b tumours were not significant in patients who had received adjuvant chemotherapy (MSF of 87%, 69% and 56%, respectively) while they were significant in patients without adjuvant chemotherapy (MFS of 70%, 68% and 42%, respectively)., CONCLUSIONS Bladder cancers invading perivesical tissue macroscopically have a greater propensity to produce lymph node metastases, local recurrence, and have lower MFS, DSS, and OS. In pN0 disease, pT3b tumours may receive more benefit from adjuvant chemotherapy., Our results could be a useful for selecting patients for adjuvant chemotherapy. [ABSTRACT FROM AUTHOR]

Simple Summary: In this study, we investigated the oncological outcomes of muscle-invasive bladder cancer patients harboring positive surgical margins following radical surgery. We found that half of them will recur within a year after treatment and will eventually die of the disease. We observed a potential role for adjuvant chemotherapy in this patient population, but clinical trials are needed in this population. Introduction: Adjuvant therapy has no defined role for patients with positive surgical margins (PSMs) following radical cystectomy (RC) for muscle-invasive bladder cancer (MIBC). The aim of our study was to describe loco-regional recurrence-free survival (LRFS), metastatic-free survival (MFS), recurrence-free survival (RFS), cancer-specific survival (CSS) and overall survival (OS) and identify predictors of each endpoint in patients with PSMs following RC for MIBC. Methods: A collaborative retrospective cohort study was conducted on 394 patients with PSMs who underwent RC for MIBC between January 2000 and December 2018 at 10 tertiary referral centers. Patients receiving perioperative radiotherapy were excluded from the study. Kaplan–Meier curves were used to estimate patient survival. Cox regression analysis was used to identify predictors of survival. Results: Median age at surgery was 70 years (IQR 62–76) with 129 (33%) and 204 (52%) patients had pT3 and pT4 tumors, respectively. Nodal metastasis (pN+) was identified in 148 (38%). Soft tissue PSMs were found in 283 (72%) patients, urethral PSMs in 65 (16.5%), and ureteral PSMs were found in 73 (18.5%). The median follow-up time was 44 months (95% CI 32–60). Median LRFS, MRFS, RFS, CSS, and OS were 14 (95% CI 11–17), 12 (95% CI 10–16), 10 (95% CI 8–12), 23 (95% CI 18–33), and 16 months (95% CI 12–19), respectively. On multivariable Cox regression analysis, the pT3–4 stage, pN+ stage, and multifocal PSMs were independent predictors of LRFS, MRFS, RFS, and OS. Adjuvant chemotherapy improved all oncological outcomes studied (p < 0.05). The number of lymph nodes removed was independently associated with better LRFS, MRFS, and RFS. Advanced age at diagnosis was independently associated with worse OS. Conclusion: Patients with PSMs following RC have poor outcomes since half of them will recur within a year and will die of their disease. Among all PSMs types, patients with multifocal PSMs harbor the worst prognosis. We observed a benefit of adjuvant chemotherapy, but clinical trials evaluating innovative adjuvant strategies for these patients remain an unmet need. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Uncomplicated cystitis is one of the most frequent community infections. We report the French results of the international ARESC study on the clinical aspects, epidemiology, and antimicrobial susceptibility of uropathogens. Patient and methods: Female patients between 18 and 65 years of age, with symptoms of uncomplicated cystitis, were investigated clinically with urinalysis and urine culture. Uropathogens were identified and their susceptibility was tested with nine antimicrobials. Results: Four thousand and four hundred patients were included, 871 in France, forming the largest national cohort. Urine culture was positive (cfu≥104/ml) in 550 (63.1%); 533 (96.9%) presented with a single bacterium infection. 488 uropathogens, collected from 479 patients, were analyzed. The most frequent were: Escherichia coli (83.8%), Staphylococcus saprophyticus (4.3%), Proteus mirabilis (3.1%), enterococci (1.2%), and Klebsiella pneumoniae (1.0%). E. coli was highly susceptible to fosfomycin (99.0%) (97.1%), nitrofurantoin (97.3%), and ciprofloxacin (98.3%). The lowest susceptibility rates were found for ampicillin (60.9%) and cotrimoxazole (87.8%). Fosfomycin (97.8%), ciprofloxacin (98.3%), and nitrofurantoin (91.5%) had the highest susceptibility rate. The lowest susceptibility rates were observed with ampicillin (61.4%) and cotrimoxazole (86.5%). Conclusions: Fosfomycin, pivmecillinam (not available in France), and nitrofurantoin have preserved their in vitro activity and are suitable for empiric therapy. Cotrimoxazole (trimethoprim+sulfamethoxazole) and fluoroquinolones are not usually recommended as first intention drugs for the empiric therapy of uncomplicated cystitis, because of increasing resistance rates. [Copyright &y& Elsevier]

Study Type - Therapy (case series) Level of Evidence 4 OBJECTIVE To evaluate the results in terms of functional results and morbidity of Z-shaped ileal neobladder performed in a single center. PATIENTS AND METHODS 329 consecutive male patients who had an orthotopic bladder replacement using the Z-shaped ileal neobladder between May 1990 and January 2009. RESULTS The mean age of the patients was 64.4 ± 9.6 years, with a mean follow-up of 59.4 ± 55 months. Eighty-three early complications in 80/294 patients (27.2%) occurred. The average Clavian rate of these early complications was 2.24. Among these, 12 complications in 12 patients (4.1%) were pouch-related, and 3 reoperations were required. Two patients died from cardiac complications. Sixty-three late complications in 60/294 patients (20.4%) were recorded. The average Clavian rate of these late complications was 2.98. Among these, 47 complications in 45/294 patients (15.3%) were pouch-related, and 18 reoperations were required, essentially for ureteral anastomosis stricture. Satisfactory daytime urinary continence was achieved in 92% of patients. Daytime continence was obtained within, on average, 6.8 ± 16.4 months. The interval between each daytime urination was 2.6 ± 0.8 h (median = 2.5 [1-5] h). Forty-four (15%) patients developed metabolic acidosis which only required oral medication. Satisfactory nocturnal urinary continence was achieved in 87% of patients. Night-time continence was obtained within, on average, 10.8 ± 22.4 months. Hyper-continence with subsequent need for CISC was observed in 4%. CONCLUSION In our series of 329 patients, compared with the other techniques, the Z-shaped ileal neobladder had an 'expected' complication rate for this high risk surgery with satisfactory daytime and night-time continence in nine out of ten patients. [ABSTRACT FROM AUTHOR]

Abstract: Background: Patients with end-stage renal disease (ESRD) are at risk of developing renal tumours. Objective: Compare clinical, pathologic, and outcome features of renal cell carcinomas (RCCs) in ESRD patients and in patients from the general population. Design, setting, and participants: Twenty-four French university departments of urology participated in this retrospective study. Intervention: All patients were treated according to current European Association of Urology guidelines. Measurements: Age, sex, symptoms, tumour staging and grading, histologic subtype, and outcome were recorded in a unique database. Categoric and continuous variables were compared by using chi-square and student statistical analyses. Cancer-specific survival (CSS) was assessed by Kaplan-Meier and Cox methods. Results and limitations: The study included 1250 RCC patients: 303 with ESRD and 947 from the general population. In the ESRD patients, age at diagnosis was younger (55±12 yr vs 62±12 yr); mean tumour size was smaller (3.7±2.6cm vs 7.3±3.8cm); asymptomatic (87% vs 44%), low-grade (68% vs 42%), and papillary tumours were more frequent (37% vs 7%); and poor performance status (PS; 24% vs 37%) and advanced T categories (≥3) were more rare (10% vs 42%). Consistently, nodal invasion (3% vs 12%) and distant metastases (2% vs 15%) occurred less frequently in ESRD patients. After a median follow-up of 33 mo (range: 1–299 mo), 13 ESRD patients (4.3%), and 261 general population patients (27.6%) had died from cancer. In univariate analysis, histologic subtype, symptoms at diagnosis, poor PS, advanced TNM stage, high Fuhrman grade, large tumour size, and non-ESRD diagnosis context were adverse predictors for survival. However, only PS, TNM stage, and Fuhrman grade remained independent CSS predictors in multivariate analysis. The limitation of this study is related to the retrospective design. Conclusions: RCC arising in native kidneys of ESRD patients seems to exhibit many favourable clinical, pathologic, and outcome features compared with those diagnosed in patients from the general population. [Copyright &y& Elsevier]

Background: The aim of this study was to characterize the aggressiveness of prostate cancer as assessed by the Gleason score (GS), the predominant Gleason pattern (pGP), and testosterone (T) serum concentration. Methods: A total of 247 patients, referred to our Department (from January 2007 to December 2009) for a radical prostatectomy, underwent preoperative T and bioavailable testosterone (samplings between 07:00 and 10:00 h). Serum determinations (radioimmunoassayed in a central laboratory). GS and pGP were determined in prostate biopsies and prostate tissue specimens. Results: In biopsy specimens, a GS7 was observed in 105 (43%) patients; 25 (10%) had pGP4. In prostate specimens, 163 (66%) had a GS7; 60 (24%) had pGP4. For prostate specimens, comparing the 75 patients with pGP4 (GS 4+3, 4+4 and 4+5) to the 172 with pGP3 (GS 3+3 and 3+4), T was lower (4.03 vs. 4.75 ng/mL, p=0.003) and prostrate-specific antigen (PSA) higher (11.1 vs. 7.3 ng/mL, p<0.00001). Extra prostatic extension and positive margins were observed more frequently (52% vs. 18%, p<0.000001 and 29% vs. 15%, p=0.009, respectively). The 40 patients with T <3.0 ng/mL were larger (+5 kg, body mass index: +1.7 kg/m2), PSA was higher (9.9 vs. 8.2 ng/mL, p=0.07). They had a higher percent of GS with pGP4: 53% vs. 25% (p=0.0008). Conclusions: Aggressiveness of the tumor cannot be properly estimated by the GS and pGP found in biopsies. The pGP in prostate specimens is of paramount importance, particularly in the case of a Gleason 7, to appreciate the outcomes and to choose the treatment. Preoperative testosterone should be added to PSA determination to improve prediction of treatment outcomes. [ABSTRACT FROM AUTHOR]

Objective. Bacteriuria is a usual complication of enterocystoplasty following cystectomy. Cranberry products may decrease the number of urinary tract infections because of a non-dialysable compound, a condensed tannin, the proanthocyanidin (PAC) type A. This study determined the effectiveness of treatment with a cranberry preparation highly dosed in proanthocyanidin A in prevention of repeated bacteriuria in patients with an ileal enterocystoplasty. Material and methods. Between November 2004 and November 2009, a controlled study was open to patients seen in consultation for follow-up after a radical cystectomy and ileal cystoplasty. Patients had a history of repeated urinary infection and/or bacteriuria during the pretreatment phase. During the treatment phase, patients received a cranberry ( Vaccinium macrocarpon) preparation highly dosed in proanthocyanidin A (36 mg measured by the dimethylaminocinnamaldehyde method), one capsule a day. The primary endpoint was the absence of bacteria in urine culture. The secondary endpoints were the presence or absence of symptoms (pain, fever), continence status and upper excretory tract enlargement. Each patient was his or her own historical control. Results. Fifteen patients were included. The median duration of the period without treatment with cranberry compound was 18.5 (1–93) months. The median duration of the period with treatment with cranberry compound was 32.8 (13–60) months. There was a significant decrease in the number of positive urine cultures during cranberry compound treatment. Conclusions. Treatment with a cranberry compound seems to be effective in reducing asymptomatic bacteriuria in patients with an ileal enterocystoplasty. These results need to be validated by further double-blind randomized studies. [ABSTRACT FROM AUTHOR]

Prognostic factors in the setting of treated metastatic renal cell carcinoma (mRCC) can theoretically predict drug response, progression-free survival or overall survival. These factors are potentially useful for informing patients and for tailoring medical treatment according to risk assessment. Prognostic factors were well defined in the era of immunotherapy. Since 2006, tyrosine kinase inhibitors and anti-angiogenic drugs have revolutionized the treatment of mRCC by improving progression-free survival and overall survival. Physicians now need new predictive tools adapted to targeted therapies. The aim of our study was to review the current knowledge about prognostic factors in mRCC by focusing on anatomical, clinical, biological, histological, radiological and molecular parameters. The most recent integrated prognostic models will be reviewed as well. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the morbidity and surgical complications of retropubic radical prostatectomy (RRP) in renal transplant recipients (RTRs) and compare these results with the observed morbidity in a control group of nontransplanted patients. Methods: We conducted a multicenter retrospective study and reviewed the charts and records of 20 RTRs who had undergone RRP for localized prostate cancer at four French renal transplant centers belonging to the Renal Transplantation Committee of the French Urological Association from April 1996 to April 2007. A total of 40 patients who had undergone RRP at the same centers, by the same surgeons, were analyzed as the case-control population. Results: The mean operating time (163 ± 41 vs 160 ± 66 minutes), blood loss (516 ± 279 vs 566 ± 449 mL), transfusion rate (20% vs 22.5%), and hospital stay (11.9 ± 5.44 vs 9.45 ± 2.8 days) were similar in the RTR and case-control populations. No graft loss or graft injury was reported in the RTRs, except for two ureteral injuries that were immediately repaired during RRP. No decrease in the kidney graft function was observed after RRP. The rate of medical complication (deep venous thrombosis, pulmonary embolism, urinary tract infection) was similar in both groups, except for the rate of bacterial systemic infection, which was significantly greater in the RTRs than in the controls (15% vs 2.5%, P = .01). Conclusions: In our study, RRP was a safe procedure to treat localized prostate cancer in RTRs. RRP resulted in the same morbidity in RTRs as in the case-control population. [Copyright &y& Elsevier]

Abstract: Objectives: To evaluate the outcome of patients with oncocytoma of the kidney diagnosed in our center by percutaneous biopsy and treated with watchful waiting. Methods: From January 1998 to April 2004, of 148 solid renal tumors biopsied in our center, 15 were renal oncocytomas. The mean (± standard deviation) follow-up was 30 ± 19.8 months. We report on the outcome of these patients. Results: The mean age at diagnosis was 57.6 ± 14.4 years, and mean tumor size was 3.49 ± 2.43 cm, corresponding to a mean tumor volume of 62.3 ± 135.4 cm3. During follow-up, 6 of 15 patients needed surgery: two partial and four total nephrectomies. Indications for surgery were initial tumor burden, greater than 0.5 cm/yr tumor growth, and patient’s preference in 1 case, 4 cases, and 1 case, respectively. The patients who received surgical treatment were significantly younger (45.5 ± 11.1 years versus 65.6 ± 10.3 years) and had more bulky tumors at diagnosis (50 ± 30.1 mm versus 27.3 ± 10.5 mm). In 1 patient, a chromophobic renal cell carcinoma was associated with the oncocytoma. All 9 patients who did not receive surgical treatment remained asymptomatic. Conclusions: The evolution of renal oncocytoma seems to be increase of tumor size with variable velocity. Treatment must be conservative. Initial management might be nonsurgical with close follow-up. Monitoring should not miss the time of conservative surgery. Initial tumor volume or fast tumor growth are indications for surgery. Partial nephrectomy, if the tumor size and localization are reasonable, is currently the technique of choice. [Copyright &y& Elsevier]

Background This national multicentre retrospective cohort study aimed to assess the long-term outcomes of dual kidney transplantation (DKT) and compare them with those obtained from single kidney transplantation (SKT). Methods Our first analysis concerned all first transplants performed between May 2002 and December 2014, from marginal donors, defined as brain death donors older than 65 years, with an estimated glomerular filtration rate (eGFR) lower than 90 mL/min/1.73 m2. The second analysis was restricted to transplants adequately allocated according to the French DKT program based on donor eGFR: DKT for eGFR between 30 and 60, SKT for eGFR between 60 and 90 mL/min/1.73 m2. Recipients younger than 65 years or with a panel-reactive antibody percentage ≥25% were excluded. Results The first analysis included 461 DKT and 1131 SKT. DKT donors were significantly older (77.6 versus 74 years), had a more frequent history of hypertension and a lower eGFR (55.1 versus 63.6 mL/min/1.73 m2). While primary nonfunction and delayed graft function did not differ between SKT and DKT, 1-year eGFR was lower in SKT recipients (39 versus 49 mL/min/1.73 m2, P < 0.001). Graft survival was significantly better in DKT, even after adjustment for recipient and donor risk factors. Nevertheless, patient survival did not differ between these groups. The second analysis included 293 DKT and 687 SKT adequately allocated with donor eGFR and displayed similar results but with a smaller benefit in terms of graft survival. Conclusions In a context of organ shortage, DKT is a good option for optimizing the use of kidneys from very expanded criteria donors. [ABSTRACT FROM AUTHOR]

Patient's preference was well balanced between enzalutamide and darolutamide. Fatigue and cognitive impairments were major concerns under new-generation hormonotherapy (NHT). For the first time, cognitive function deterioration under NHT was investigated prospectively. Darolutamide was associated with a significant benefit in verbal learning compared with enzalutamide. Darolutamide and enzalutamide are second-generation androgen receptor inhibitors with activity in men with castrate-resistant prostate cancer (CRPC) and different toxicity profiles. ODENZA is a prospective, randomized, multicenter, cross-over, phase 2 trial designed to assess preference between darolutamide and enzalutamide in men with asymptomatic or mildly symptomatic metastatic CRPC (mCRPC). Patients were randomized 1:1 to receive either darolutamide 1200 mg/d for 12 wk followed by enzalutamide 160 mg/d for 12 wk or enzalutamide followed by darolutamide. In both arms, the second treatment was given in absence of cancer progression. The primary endpoint was patient preference between the two drugs, as assessed by a preference questionnaire (p value calculated with the Prescott test). After week 24, patients entered an extension period during which they received their preferred treatment until progression or toxicity. The main secondary objectives included reasons for patient preference, response at week 12, tolerance of each drug, and measurement compared with baseline of cognitive outcomes assessed using tablet questionnaires. Overall, 249 patients, with a median age of 72 yr, were randomized. Among the 200 patients who fulfilled the preplanned criteria for the evaluation of the primary endpoint of preference, 97 (49% [41; 56]), 80 (40% [33; 47]), and 23 (12% [7; 16]) chose darolutamide, chose enzalutamide, and had no preference, respectively (p = 0.92). Reduced fatigue, easier administration, and better quality of life were the main criteria that influenced patient choice. A moderate benefit in episodic memory from darolutamide was observed for the acquisition of new information (least square [LS] means difference = 2.2, effect size = 0.5) and for the recall of that information after a brief delay (LS means difference = 0.7, effect size = 0.3). Using the Brief Fatigue Inventory questionnaire, patients reported greater fatigue with enzalutamide (3.3 [3.0; 3.6]) than with darolutamide (2.7 [2.4; 3.0]). There was no difference in terms of depression, seizures, and falls. The study did not show a difference in preference between the two treatments. In men with mCRPC, darolutamide was associated with a clinically meaningful benefit in episodic memory and less fatigue compared with enzalutamide. Preference between darolutamide and enzalutamide was well balanced in men with castrate-resistant prostate cancer. Darolutamide was associated with a significant benefit in verbal learning and less fatigue compared with enzalutamide. [ABSTRACT FROM AUTHOR]

The objective of the European Association of Urology guidelines is to provide practical evidence-based recommendations and consensus statements on the clinical management of urological conditions, with a focus on diagnosis and treatment. In this context the summary of the 2023 guideline on muscle-invasive and metastatic bladder cancer provides updated information on the diagnosis and treatment of this disease for incorporation in clinical practice. We present an overview of the updated 2023 European Association of Urology (EAU) guidelines for muscle-invasive and metastatic bladder cancer (MMIBC). To provide practical evidence-based recommendations and consensus statements on the clinical management of MMIBC with a focus on diagnosis and treatment. A broad and comprehensive scoping exercise covering all areas of the MMIBC guidelines has been performed annually since 2017. Searches cover the Medline, EMBASE, and Cochrane Libraries databases for yearly guideline updates. A level of evidence and strength of recommendation are assigned. The evidence cutoff date for the 2023 MIBC guidelines was May 4, 2022. Patients should be counselled regarding risk factors for bladder cancer. Pathologists should describe tumour and lymph nodes in detail, including the presence of histological subtypes. The importance of the presence or absence of urothelial carcinoma (UC) in the prostatic urethra is emphasised. Magnetic resonance imaging (MRI) of the bladder is superior to computed tomography (CT) for disease staging, specifically in differentiating T1 from T2 disease, and may lead to a change in treatment approach in patients at high risk of an invasive tumour. Imaging of the upper urinary tract, lymph nodes, and distant metastasis is performed with CT or MRI; the additional value of flurodeoxyglucose positron emission tomography/CT still needs to be determined. Frail and comorbid patients should be evaluated by a multidisciplinary team. Postoperative histology remains the most important prognostic variable, while circulating tumour DNA appears to be an interesting predictive marker. Neoadjuvant systemic therapy remains cisplatin-based. In motivated and selected women and men, sexual organ–preserving cystectomy results in better functional outcomes without compromising oncological outcomes. Robotic and open cystectomy have comparable outcomes and should be combined with (extended) lymph node dissection. The diversion type is an individual choice after taking patient and tumour characteristics into account. Radical cystectomy remains a highly complex procedure with considerable morbidity and risk of mortality, although lower rates are observed for higher hospital volumes (>20 cases/yr). With proper patient selection, trimodal therapy (chemoradiation) has comparable outcomes to radical cystectomy. Adjuvant chemotherapy after surgery improves disease-specific survival and overall survival (OS) in patients with high-risk disease who did not receive neoadjuvant treatment, and is strongly recommended. There is a weak recommendation for adjuvant nivolumab, as OS data are not yet available. Health-related quality of life should be assessed using validated questionnaires at baseline and after treatment. Surveillance is needed to monitor for recurrent cancer and functional outcomes. Recurrences detected on follow-up seem to have better prognosis than symptomatic recurrences. This summary of the 2023 EAU guidelines provides updated information on the diagnosis and treatment of MMIBC for incorporation into clinical practice. The European Association of Urology guidelines panel on muscle-invasive and metastatic bladder cancer has released an updated version of the guideline containing information on diagnosis and treatment of this disease. Recommendations are based on studies published up to May 4, 2022. Surgical removal of the bladder and bladder preservation are discussed, as well as updates on the use of chemotherapy and immunotherapy in localised and metastatic disease. [ABSTRACT FROM AUTHOR]

Background: Upper urinary tract urothelial carcinoma (UTUC) is often locally advanced at initial diagnosis and is associated with high recurrence and mortality rates after radical nephroureterectomy (RNU). Adjuvant platinum-based chemotherapy has shown a recurrence-free survival benefit in a randomised phase III trial, while neoadjuvant treatment seems promising in retrospective series. On the contrary, little is known about the role of perioperative immunotherapy and its combination with chemotherapy for UTUC patients, although initial positive results have been published for muscle-invasive bladder cancer. Study design and endpoints: Against this backdrop, we are running a multi-centre single-arm phase 2 trial of neoadjuvant Durvalumab, a monoclonal antibody targeting programmed cell death ligand 1, combined with Gemcitabine and Cisplatin or Carboplatin for high-risk UTUC patients. The primary outcome is pathological complete response rate at RNU. Secondary endpoints include the partial pathological response rate, safety, as well as disease-free and overall survival. A biomarker analysis is also planned. Patients and interventions: Included patients must have a good performance status and harbour a non-metastatic UTUC, considered at high risk of progression, defined as either biopsy-proven high-grade disease or invasive features at imaging with or, more recently, without high-grade cytology at the multidisciplinary team discretion, as specified in the latest amendment. Enrolled patients receive 3 cycles of neoadjuvant immuno-chemotherapy before RNU, and the standard of care thereafter. The trial is registered as NCT04617756 and is supervised by an independent data monitoring committee. [ABSTRACT FROM AUTHOR]

Background: Prostate cancer among black men is known to have specific molecular characteristics, especially the androgen receptor or enzymes related to the androgen metabolism. These targets are keys to the action of new hormonal therapies. Nevertheless, literature has a lack of data regarding black men. We aimed to gather the available literature data on new hormonal therapies among black populations.Methods: We conducted a literature review from the PubMed / MEDLINE database until October 2020. All clinical studies of new hormonal therapies and black populations, regardless of methodology, were included.Results: Four studies provided data on new hormonal therapies in black populations. Three studies reported a PSA decline in black patients treated with Abiraterone, higher in black men than in white men. Overall survival also appears to be higher in black patients treated with Abiraterone only or first.Conclusion: Few articles have evaluated the effectiveness and safety of use of these treatments among black populations. The first results seem to show that Abiraterone can provide a benefit in overall survival in black populations. Prospective studies are needed to answer these questions in the future. [ABSTRACT FROM AUTHOR]

Background: The insulin growth factor (IGF) pathway has been proposed as a potential therapeutic target in bladder cancer. We characterized the expression of components of the IGF pathway - insulin growth factor receptors (INSR, IGF1R, IGF2R), ligands (INS, IGF1, IGF2), and binding proteins (IGFBP1-7, IGF2BP1-3) - in bladder cancer and its correlation with IGF1R activation, and the anti-proliferative efficacy of an IGF1R kinase inhibitor in this setting.Methods: We analyzed transcriptomic data from two independent bladder cancer datasets, corresponding to 200 tumoral and five normal urothelium samples. We evaluated the activation status of the IGF pathway in bladder tumors, by assessing IGF1R phosphorylation and evaluating its correlation with mRNA levels for IGF pathway components. We finally evaluated the correlation between inhibition of proliferation by a selective inhibitor of the IGF1R kinase (AEW541), reported in 13 bladder cancer derived cell lines by the Cancer Cell Line Encyclopedia Consortium and mRNA levels for IGF pathway components.Results: IGF1R expression and activation were stronger in non-muscle-invasive than in muscle-invasive bladder tumors. There was a significant inverse correlation between IGF1R phosphorylation and IGFBP5 expression in tumors. Consistent with this finding, the inhibition of bladder cell line viability by IGF1R inhibitor was also inversely correlated with IGFBP5 expression.Conclusion: The IGF pathway is activated and therefore a potential therapeutic target for non muscle-invasive bladder tumors and IGFBP5 could be used as a surrogate marker for predicting tumor sensitivity to anti-IGF therapy. [ABSTRACT FROM AUTHOR]

Background: Parastomal incisional hernia (PH) is a frequent complication following the creation of an ileal conduit (IC), and it can be a significant detriment to quality of life. The aim of this study was to evaluate outcomes of PH repair following IC for urinary diversion. Method: A multicenter retrospective study was conducted of 6 academic hospitals in France. The study's population included patients who underwent surgical treatment for parastomal hernia following IC creation from 2013 to 2021. Results: Fifty-one patients were included in the study. Median follow up was 15.3 months. Eighteen patients presented with a recurrence (35%), with a median time to recurrence of 11.1 months. The vast majority of PH repair was performed through an open approach (88%). With regard to technique, Keyhole was the most reported technique (46%) followed by Sugarbaker (22%) and suture only (20%). The Keyhole technique was associated with a higher risk of recurrence compared to the Sugarbaker technique (52% vs 10%, p = 0.046). Overall, there was a 7.8% rate of major complications without a statistical difference between PH repair techniques for major complications. Conclusion: Surgical treatment of parastomal hernia following IC was associated with a high risk of recurrence. Novel surgical approaches to PH repair should be considered. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate variant histologies (VHs) for disease‐specific survival (DSS) in patients with invasive urothelial bladder cancer (BCa) undergoing radical cystectomy (RC). Materials and Methods: We analysed a multi‐institutional cohort of 1082 patients treated with upfront RC for cT1‐4aN0M0 urothelial BCa at eight centres. Univariable and multivariable Cox' regression analyses were used to assess the effect of different VHs on DSS in overall cohort and three stage‐based analyses. The stages were defined as 'organ‐confined' (≤pT2N0), 'locally advanced' (pT3‐4N0) and 'node‐positive' (pTanyN1‐3). Results: Overall, 784 patients (72.5%) had pure urothelial carcinoma (UC), while the remaining 298 (27.5%) harboured a VH. Squamous differentiation was the most common VH, observed in 166 patients (15.3%), followed by micropapillary (40 patients [3.7%]), sarcomatoid (29 patients [2.7%]), glandular (18 patients [1.7%]), lymphoepithelioma‐like (14 patients [1.3%]), small‐cell (13 patients [1.2%]), clear‐cell (eight patients [0.7%]), nested (seven patients [0.6%]) and plasmacytoid VH (three patients [0.3%]). The median follow‐up was 2.3 years. Overall, 534 (49.4%) disease‐related deaths occurred. In uni‐ and multivariable analyses, plasmacytoid and small‐cell VHs were associated with worse DSS in the overall cohort (both P = 0.04). In univariable analyses, sarcomatoid VH was significantly associated with worse DSS, while lymphoepithelioma‐like VH had favourable DSS compared to pure UC. Clear‐cell (P = 0.015) and small‐cell (P = 0.011) VH were associated with worse DSS in the organ‐confined and node‐positive cohorts, respectively. Conclusions: More than 25% of patients harboured a VH at time of RC. Compared to pure UC, clear‐cell, plasmacytoid, small‐cell and sarcomatoid VHs were associated with worse DSS, while lymphoepithelioma‐like VH was characterized by a DSS benefit. Accurate pathological diagnosis of VHs may ensure tailored counselling to identify patients who require more intensive management. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate variant histologies (VHs) for disease‐specific survival (DSS) in patients with invasive urothelial bladder cancer (BCa) undergoing radical cystectomy (RC). Materials and Methods: We analysed a multi‐institutional cohort of 1082 patients treated with upfront RC for cT1‐4aN0M0 urothelial BCa at eight centres. Univariable and multivariable Cox' regression analyses were used to assess the effect of different VHs on DSS in overall cohort and three stage‐based analyses. The stages were defined as 'organ‐confined' (≤pT2N0), 'locally advanced' (pT3‐4N0) and 'node‐positive' (pTanyN1‐3). Results: Overall, 784 patients (72.5%) had pure urothelial carcinoma (UC), while the remaining 298 (27.5%) harboured a VH. Squamous differentiation was the most common VH, observed in 166 patients (15.3%), followed by micropapillary (40 patients [3.7%]), sarcomatoid (29 patients [2.7%]), glandular (18 patients [1.7%]), lymphoepithelioma‐like (14 patients [1.3%]), small‐cell (13 patients [1.2%]), clear‐cell (eight patients [0.7%]), nested (seven patients [0.6%]) and plasmacytoid VH (three patients [0.3%]). The median follow‐up was 2.3 years. Overall, 534 (49.4%) disease‐related deaths occurred. In uni‐ and multivariable analyses, plasmacytoid and small‐cell VHs were associated with worse DSS in the overall cohort (both P = 0.04). In univariable analyses, sarcomatoid VH was significantly associated with worse DSS, while lymphoepithelioma‐like VH had favourable DSS compared to pure UC. Clear‐cell (P = 0.015) and small‐cell (P = 0.011) VH were associated with worse DSS in the organ‐confined and node‐positive cohorts, respectively. Conclusions: More than 25% of patients harboured a VH at time of RC. Compared to pure UC, clear‐cell, plasmacytoid, small‐cell and sarcomatoid VHs were associated with worse DSS, while lymphoepithelioma‐like VH was characterized by a DSS benefit. Accurate pathological diagnosis of VHs may ensure tailored counselling to identify patients who require more intensive management. [ABSTRACT FROM AUTHOR]

Objectives To retrospectively assess the long-term outcome of patients initially diagnosed with TaG1 non–muscle-invasive bladder cancer (NMIBC) with no immediate postoperative instillation of intravesical chemotherapy and evaluate the reproducibility of the European Organization for Research and Treatment of Cancer (EORTC) scoring system for predicting bladder cancer outcome. Methods and materials A retrospective analysis of 481 consecutive cases of initially diagnosed TaG1 NMIBC according to the 1973 World Health Organization classification between 1995 and 2008 in a single institution was performed. Time to first recurrence, time to progression to T1 or G3 bladder cancer, and time to progression to muscle-invasive bladder cancer were studied. Time to event distributions was estimated by means of cumulative incidence functions to accurately take into account the patients who died (competing risk) before recurrence or progression. The Harrell c statistic calculation was used for our study׳s data results as well the original data from EORTC to compare the predictive power of a survival model. Results The median follow-up was 88 months (interquartile range: 51–135 mo). The 10-year recurrence-free, T1 or G3 NMIBC progression-free, and muscle-invasive bladder cancer progression-free survival rates were 64.2%, 96.6%, and 97%, respectively. In multivariate analysis, tumor size and number of lesions were prognostic variables of the risk of recurrence. In our study and EORTC data sets, the Harrell c values obtained were c = 0.85 (95% CI: [0.75, 0.93]) and c = 0.85 (95% CI: [0.75, 0.93]), respectively. Conclusion Our study reports a detailed and extensive outcome of TaG1 NMIBC treated by TURB with no immediate postoperative intravesical instillation of chemotherapy. Our results suggest that the EORTC is a useful external validation scoring system for predicting bladder cancer outcome. [ABSTRACT FROM AUTHOR]

Introduction: Mutations in the TP53 gene are indicative of worse outcome in bladder cancer and are usually assessed by immunohistochemistry. To define p53-overexpression, a threshold of >10% is most commonly used (cut-off1). Recently, a novel cut-off (aberrant = 0% or ≥50%) (cut-off2) showed better correlation to clinical outcome. In this study, we evaluate the association between p53-immunohistochemistry cut-offs, clinico-pathological variables and disease-specific survival (DSS). Methods: Seven-hundred-fifty chemotherapy-naïve patients who underwent radical cystectomy were included (92% muscle-invasive bladder cancer. In addition to cut-off1 and cut-off2, a third cut-off (cut-off3) was determined based on the highest Youden-index value. Cut-off values were associated with clinico-pathological variables and FGFR3 mutation status. The Kaplan-Meier method was used to estimate DSS. Results: Aberrant p53-expression was found in 489 (65%) (cut-off1) and 466 (62%) (cut-off2) tumors. Cut-off3 was determined at 25% and aberrant p53-expression in 410 cases (55%) (cutoff3). p53-expression levels were significantly associated with higher pT-stage (cut-off1/2/3: P = 0.047, P = 0.006 and P = 0.0002, respectively), higher grade (all, P < 0.0001), and FGFR3 wild-type (cut-off1: P = 0.02, cut-offs2&3: P = 0.001). Median follow-up was 5.3 years (interquartile range, 4.0-6.0 years). p53-expression was not associated with DSS for any of the three cut-offs (cut-off1/2/3: P-log-rank = 0.566, 0.77 and 0.50, respectively). If we only considered locally advanced bladder cancer, results on DSS remained non-significant. Conclusion: This multi-center, multi-laboratory study showed that, regardless of the cut-off used, p53-immunohistochemistry did not enable selection of patients with worse outcome. Our results suggest that p53-immunohistochemistry alone is not suitable to guide clinical decision making after radical cystectomy. [ABSTRACT FROM AUTHOR]

Objective: To analyze de novo graft carcinoma characteristics from our updated national multicentric retrospective cohort.Methods: Thirty-two transplant centers have retrospectively completed the database. This database concerns all kidney graft tumors including urothelial, and others type but excludes renal lymphomas over 31 years.Results: One hundred and fifty twokidney graft carcinomas were diagnosed in functional grafts. Among them 130 tumors were Renal Cell Carcinomas. The calculated incidence was 0.18%. Median age of the allograft at diagnosis was 45.4 years old. The median time between transplantation and diagnosis was 147.1 months. 60 tumors were papillary carcinomas and 64 were clear cell carcinomas. Median tumor size was 25 mm. 18, 64, 21 and 1 tumors were respectively Fuhrman grade 1, 2, 3 and 4. Nephron sparing surgery (NSS) was performed on 68 (52.3%) recipients. Ablative therapy was performed in 23 cases (17.7%). Specific survival rate was 96.8%.Conclusion: This study confirmed that renal graft carcinomas are a different entity: with a younger age of diagnosis; a lower stage at diagnosis; a higher incidence of papillary subtypes. [ABSTRACT FROM AUTHOR]

Aim: 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. Methods: 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. Discussion: 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. [ABSTRACT FROM AUTHOR]

Simple Summary: Radical nephroureterectomy (RNU) is the standard treatment for high-risk upper tract urothelial carcinoma (UTUC). It implies significant reduction in the renal function, compromising adjuvant chemotherapy administration and leading to risk of end stage renal disease in frail patients. Distal ureterectomy (DU) might be an alternative for tumors of the distal ureter but its indications remain unclear mainly due to concern about potential upper tract recurrences. The objective of our retrospective study was to determine the oncologic outcomes of DU for high-risk UTUC of the pelvic ureter, and to assess factors associated with recurrence in the particular population. We showed that oncological outcomes after DU were similar to those after RNU. Some of the classical prognostic factors after RNU were not identified in this cohort, pinpointing the necessity to consider tumors of the distal ureter as a specific entity. 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. [ABSTRACT FROM AUTHOR]

Introduction and hypothesis: Tapes for stress urinary incontinence (SUI) and meshes for pelvic organ prolapse can result in postoperative complications, such as urethral (UP) or bladder (BP) perforations. Martius fat pad (MFP) is an historic procedure, widely used to treat lower urinary tract (LUT) fistulae. We report our experience with the insertion of the biological small intestinal submucosa (SIS) xenograft as an alternative to MFP in these prosthetic complications. Methods: We conducted a retrospective, monocentric study which included all patients who underwent SIS insertion during surgical removal of tape/vaginal mesh for UP or BP from 2011 to 2019. Preoperative assessment was based on history, symptoms, physical examination and urethrocystoscopy. Primary outcome was successful repair defined as absence of any LUT defect. Secondary outcomes were complications, LUT symptoms, pain and additional SUI surgical procedures. Results: Thirty-eight patients were included. Twenty-six had a UP and eight a BP. In four cases, perforation involved both the bladder neck and urethra. All LUT defects were cured. Six postoperative complications were reported (five of grade ≤ 2 and one of grade 3b according to the Clavien-Dindo classification). At the mean follow-up of 37.2 (range 6–98) months, 14 patients (36.8%) presenting a postoperative SUI underwent a SUI surgical procedure and 1 patient had a laparoscopic sacrocolpopexy for cystocele recurrence. Conclusion: Absorbable SIS xenograft is an effective and safe graft for the management of lower urinary tract tape and mesh perforations. The cost has to be balanced with the good results, short operative time and no fat pad complications as in MFP. [ABSTRACT FROM AUTHOR]

Patients with treatment-naïve metastatic urothelial carcinoma are grouped according to platinum eligibility based on clear definitions. In general, first-line treatment consists of platinum-based chemotherapy in which cisplatin is to be preferred to carboplatin. Patients who are cisplatin ineligible but carboplatin eligible should receive carboplatin-gemcitabine combination chemotherapy. In case of positive programmed death ligand 1 (PD-L1) status, treatment with checkpoint inhibitors (atezolizumab or pembrolizumab) could be an alternative option. Patients unfit for both cisplatin and carboplatin (platinum unfit) can be considered for immunotherapy (U.S. Food and Drug Administration approved irrespective of PD-L1 status and European Medicines Agency approved only for PD-L1 positive) or can receive best supportive care. Treatment of metastatic urothelial carcinoma is currently undergoing a rapid evolution. This overview presents the updated European Association of Urology (EAU) guidelines for metastatic urothelial carcinoma. A comprehensive scoping exercise covering the topic of metastatic urothelial carcinoma is performed annually by the Guidelines Panel. Databases covered by the search included Medline, EMBASE, and the Cochrane Libraries, resulting in yearly guideline updates. Platinum-based chemotherapy is the recommended first-line standard therapy for all patients fit to receive either cisplatin or carboplatin. Patients positive for programmed death ligand 1 (PD-L1) and ineligible for cisplatin may receive immunotherapy (atezolizumab or pembrolizumab). In case of nonprogressive disease on platinum-based chemotherapy, subsequent maintenance immunotherapy (avelumab) is recommended. For patients without maintenance therapy, the recommended second-line regimen is immunotherapy (pembrolizumab). Later-line treatment has undergone recent advances: the antibody-drug conjugate enfortumab vedotin demonstrated improved overall survival and the fibroblast growth factor receptor (FGFR) inhibitor erdafitinib appears active in case of FGFR3 alterations. This 2021 update of the EAU guideline provides detailed and contemporary information on the treatment of metastatic urothelial carcinoma for incorporation into clinical practice. In recent years, several new treatment options have been introduced for patients with metastatic urothelial cancer (including bladder cancer and cancer of the upper urinary tract and urethra). These include immunotherapy and targeted treatments. This updated guideline informs clinicians and patients about optimal tailoring of treatment of affected patients. [ABSTRACT FROM AUTHOR]

There are conflicting data with regards to the link between diet and the prostate cancer. The purpose of this study was to assess the association of dietary factors with incidence, prevalence and mortality rates of prostate cancer worldwide. We conducted an ecological study including 170 countries, whose data on incidence, prevalence and mortality rates of prostate cancer, dietary factors, and potentially confounding factors were available and collected in May 2020. Univariable and multivariable linear regression analyses were used. Consumption of nuts and seeds was inversely associated with incidence, prevalence and mortality rates of prostate cancer (β −0.7, P < 0.001; β −2.1, P < 0.001; β −0.1, P = 0.02; respectively). Intake of alcohol was associated with increased incidence, prevalence and mortality rates of prostate cancer (β 1.8, P < 0.001; β 4.5, P < 0.001; β 0.4, P < 0.001; respectively). Consumption of processed meats was also associated with increased incidence and prevalence rates of prostate cancer (β 0.6, P = 0.003; β 2.8, P = 0.001; respectively). These data suggest that consumption of nuts and seeds have a protective effect against prostate carcinogenesis, progression, and metastasis, while alcohol and processed meat increase these risks. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the risk factors associated with positive surgical margins' (PSMs) location and their impact on disease-specific survival (DSS) in patients with bladder cancer (BCa) undergoing radical cystectomy (RC). Methods: We analyzed a large multi-institutional cohort of patients treated with upfront RC for non-metastatic (cT1-4aN0M0) BCa. Multivariable binomial logistic regression analyses were used to assess the risk of PSMs at RC for each location after adjusting for clinicopathological covariates. The Kaplan–Meier method was used to estimate DSS stratified by margins' status and location. Log-rank statistics and Cox' regression models were used to determine significance. Results: A total of 1058 patients were included and 108 (10.2%) patients had PSMs. PSMs were located at soft-tissue, ureter(s), and urethra in 57 (5.4%), 30 (2.8%) and 21 (2.0%) patients, respectively. At multivariable analysis, soft-tissue PSMs were independently associated with pathological stage T4 (pT4) (Odds ratio (OR) 6.20, p < 0.001) and lymph-node metastases (OR 1.86, p = 0.04). Concomitant carcinoma-in-situ (CIS) was an independent risk factor for ureteric PSMs (OR 6.31, p = 0.003). Finally, urethral PSMs were independently correlated with pT4-stage (OR 5.10, p = 0.01). The estimated 3-years DSS rates were 58.2%, 32.4%, 50.1%, and 40.3% for negative SMs, soft-tissue-, ureteric- and urethral PSMs, respectively (log-rank; p < 0.001). Conclusions: PSMs' location represents distinct risk factors' patterns. Concomitant CIS was associated with ureteric PSMs. Urethral and soft-tissue PSM showed worse DSS rates. Our results suggest that clinical decision-making paradigms on adjuvant treatment and surveillance might be adapted based on PSM and their location. [ABSTRACT FROM AUTHOR]

Purpose: To assess the association between PD-L1 expression and disease-free survival (DFS) in High-Risk Non-Muscle Invasive Bladder Cancer (HR-NMIBC) patients treated with intravesical Bacillus Calmette–Guerin (BCG) instillations (IBI). Methods: Retrospective study in five French centres between 2001 and 2015. Participants were 140 patients with histologically confirmed HR-NMIBC. All patients received induction and maintenance IBI. Pathological stage/grade, concomitant carcinoma in situ, lesion number and tumour size were recorded. CD3, CD8 and PD-L1 expression in tumour cells and in T cells in the tumour microenvironment (TME) was determined immunohistochemically. Median follow-up was 54.2 months. The primary outcome measure was DFS. Univariable and multivariable analyses were performed using the log rank test and Cox proportional hazards model. Results: Of the 140 NMIBC, 52 (37.1%) were Ta, 88 (62.9%) were T1 and 100% were high grade. Median number of maintenance IBI was six (range 1–30). Twenty-five (17.9%) patients had recurrence/progression. In multivariable analysis, age (HR 1.07 [95% CI 1.02–1.13], p = 0.009), PD-L1 expression in tumour cells (HR per 10 units = 1.96 [95% CI 1.28–3.00], p = 0.02) and CD3/CD8 ratio (HR per 10 units = 3.38 [95% CI 1.61–7.11], p = 0.01) were significantly associated with DFS. However, using the cut-off corresponding for each PD-L1 antibodies, PD-L1 + status was not associated with DFS. Conclusion: Despite an association between PD-L1 expression and BCG failure in HR-NMIBC, the PD-L1 + status was not a prognostic factor in the response of BCG. Moreover, we confirmed the key role played by the IC within the microenvironment in BCG treatment. These findings highlighted the rationale to combine BCG and PD-L1/PD-1 antibodies in early bladder cancer. [ABSTRACT FROM AUTHOR]

This overview presents the updated European Association of Urology (EAU) guidelines for muscle-invasive and metastatic bladder cancer (MMIBC). To provide practical evidence-based recommendations and consensus statements on the clinical management of MMIBC with a focus on diagnosis and treatment. A broad and comprehensive scoping exercise covering all areas of the MMIBC guideline has been performed annually since its 2017 publication (based on the 2016 guideline). Databases covered by the search included Medline, EMBASE, and the Cochrane Libraries, resulting in yearly guideline updates. A level of evidence and a grade of recommendation were assigned. Additionally, the results of a collaborative multistakeholder consensus project on advanced bladder cancer (BC) have been incorporated in the 2020 guidelines, addressing those areas where it is unlikely that prospective comparative studies will be conducted. Variant histologies are increasingly reported in invasive BC and are relevant for treatment and prognosis. Staging is preferably done with (enhanced) computerised tomography scanning. Treatment decisions are still largely based on clinical factors. Radical cystectomy (RC) with lymph node dissection remains the recommended treatment in highest-risk non–muscle-invasive and muscle-invasive nonmetastatic BC, preceded by cisplatin-based neoadjuvant chemotherapy (NAC) for invasive tumours in "fit" patients. Selected men and women benefit from sexuality sparing RC, although this is not recommended as standard therapy. Open and robotic RC show comparable outcomes, provided the procedure is performed in experienced centres. For open RC 10, the minimum selected case load is 10 procedures per year. If bladder preservation is considered, chemoradiation is an alternative in well-selected patients without carcinoma in situ and after maximal resection. Adjuvant chemotherapy should be considered if no NAC was given. Perioperative immunotherapy can be offered in clinical trial setting. For fit metastatic patients, cisplatin-based chemotherapy remains the first choice. In cisplatin-ineligible patients, immunotherapy in Programmed Death Ligand 1 (PD-L1)-positive patients or carboplatin in PD-L1–negative patients is recommended. For second-line treatment in metastatic disease, pembrolizumab is recommended. Postchemotherapy surgery may prolong survival in responders. Quality of life should be monitored in all phases of treatment and follow-up. The extended version of the guidelines is available at the EAU website: https://uroweb.org/guideline/bladder-cancer-muscle-invasive-and-metastatic/. This summary of the 2020 EAU MMIBC guideline provides updated information on the diagnosis and treatment of MMIBC for incorporation into clinical practice. The European Association of Urology Muscle-invasive and Metastatic Bladder Cancer (MMIBC) Panel has released an updated version of their guideline, which contains information on histology, staging, prognostic factors, and treatment of MMIBC. The recommendations are based on the current literature (until the end of 2019), with emphasis on high-level data from randomised clinical trials and meta-analyses and on the findings of an international consensus meeting. Surgical removal of the bladder and bladder preservation are discussed, as well as the use of chemotherapy and immunotherapy in localised and metastatic disease. Radical cystectomy with urinary diversion remains the mainstay of managing muscle-invasive bladder cancer (MIBC). The use of neoadjuvant chemotherapy (NAC) has improved overall survival rates, but selection of patients who will benefit most from NAC remains challenging. In case bladder-preserving strategies are considered, patient stratification according to their risk profile is imperative and management should be discussed in a multidisciplinary team. As yet, there are no validated prognostic molecular markers to guide the clinical management of MIBC. In a metastatic setting, cisplatin-based chemotherapy remains the first choice in fit patients. In unfit patients, based on interim results from two on-going clinical trials, first-line treatment with pembrolizumab or atezolizumab for urothelial cancer is restricted to Programmed Death Ligand 1-positive patients only. [ABSTRACT FROM AUTHOR]

Fibroblast growth factor receptor 3 (FGFR3) is an actionable target in bladder cancer (BC). FGFR3 mutations are common in noninvasive BC and associated with favorable BC prognosis. Overexpression was reported in up to 40% of FGFR3 wild-type muscle-invasive BC. We analyzed FGFR3 mutations, FGFR3, and p53 protein expression and assessed their prognostic value in a cohort of 1000 chemotherapy-naive radical cystectomy specimens. FGFR3 mutations were found in 11%, FGFR3 overexpression was found in 28%, and p53 overexpression was found in 69% of tumors. Among FGFR3 mutant tumors, 73% had FGFR3 overexpression versus 22% among FGFR3 wild-type tumors. FGFR3 mutations were significantly associated with lower pT stage, tumor grade, absence of carcinoma in situ, pN0, low-level p53, and longer disease-specific survival (DSS). FGFR3 overexpression was associated only with lower pT stage and tumor grade. Moreover, FGFR3 overexpression was not associated with DSS in patients with FGFR3 wild-type tumors. In conclusion, FGFR3 mutations identified patients with favorable BC at cystectomy. Our results suggest that FGFR3 mutations have a driver role and are functionally distinct from FGFR3 overexpression. Hence, patients with FGFR3 mutations would be more likely to benefit from anti-FGFR3 therapy. Ideally, further research is needed to test this hypothesis. Oncogenic fibroblast growth factor receptor 3 (FGFR3) mutations are very common in bladder cancer. In this report, we found that these FGFR3 mutations were associated with favorable features and prognosis of bladder cancer compared with patients with FGFR3 overexpressed tumors only. As a consequence, patients with FGFR3 mutant tumors would be more likely to benefit from anti-FGFR3 therapy than patients with FGFR3 protein overexpression only. Oncogenic fibroblast growth factor receptor 3 (FGFR3) mutations were associated with favorable bladder cancer in a series of 1000 radical cystectomy cases. Moreover, patients with FGFR3 mutant tumors would be more likely to benefit from anti-FGFR3 therapy than patients with overexpression only. [ABSTRACT FROM AUTHOR]

Objectives: Preoperative 18F-fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) is controversial to assess lymph node (LN) staging in patients with invasive bladder cancer. We proposed to use the maximum standardized uptake value (SUVmax) associated with axial-based LN size to improve the detection of regional LN metastasis.Methods: From May 2015 to May 2017, we prospectively included patients with urothelial bladder cancer who underwent radical cystectomy with extended pelvic LN dissection. All patients underwent preoperative 18F-FDG PET/CT staging before surgery. The gold standard comparator was the pathological examination of resected LNs. The data were reported on a regional per area- and patient-based model according to SUVmax values and axial-based LN size criteria.Results: In total, 1012 LNs were identified in 61 patients with clinically localized invasive bladder cancer who underwent radical cystectomy and extended pelvic LN dissection. Loco-regional involvement of 24 LN areas was confirmed in 17 patients. In per area analysis, diagnostic accuracy of PET/CT and CT alone were respectively 84% and 78% (p = 0.039). On patient-based analysis, combined PET/CT correctly classified pelvic LN status in 5/61 (+ 8%) additional patients using optimal thresholds compared to CT alone, with accuracies of 82% and 74%, respectively (p = 0.13).Conclusion: Combining SUVmax and axial-based LN size criteria using 18F-FDG PET/CT improved the diagnostic accuracy for preoperative LN staging in patients with invasive bladder cancer, in per area analysis.Key Points: • Combining metabolical and morphological features using18F-FDG PET/CT improves the detection of malignant lymph node in patients with bladder cancer. • 18 F-FDG PET/CT may help for initial staging of patients with muscle invasive bladder cancer. [ABSTRACT FROM AUTHOR]

Aim: To assess the prognostic value of multiple recurrences on the risk of progression in a large cohort of TaG1 bladder cancer of low and intermediate risk based on the EORTC score and to evaluate prognostic factors of multiple recurrences. Materials and methods: We retrospectively analyzed a French cohort of 470 patients with primary TaG1 bladder cancer diagnosed between 1986 and 2010 and followed until 2012. They were classified at low and intermediate risk using the EORTC risk score. Associations between the number of recurrences and the risk of progression to high grade Ta/T1 bladder cancer and progression to muscle-invasive disease were assessed. The characteristics of recurrences, as occurrence time or localization, and risk of other recurrences were evaluated. Results: Out of 470 patients, 251 had recurrence, 34 progressed to high grade Ta/T1 and 17 to muscle-invasive disease, including 4 who had non muscle-invasive progression first. The median follow-up was 7.2 years (interquartile range: 4.2–10.9). In half the progressions, no previous recurrence was observed. No association between the number of recurrences and the risk of progression was detected. Even after 5 years free of event, patients had a 15% risk of recurrence. History of two or more recurrences increased by 4.5 the risk of subsequent recurrence. Time between two recurrences inferior to six months and multifocal localization increased the risk of recurrence. Conclusion: Surveillance of patients with TaG1 should be continued beyond 5 years of follow-up. However, cystoscopy exams could be spaced after 5 years. Multiple TaG1 recurrences did not appear to be prognostic for disease progression, but increased significantly the risk of subsequent recurrences. Short time between two recurrences and multifocal localization may serve to adapt monitoring of patients with TaG1 Bladder cancer. [ABSTRACT FROM AUTHOR]

Abstract Introduction Assessment of tumour-infiltrating lymphocytes (TILs) can provide important prognostic information in various cancers and may be of value in predicting response to immunotherapy. The objective of the present study was to investigate the association of stromal lymphocytic infiltration with clinicopathological parameters and their correlation with outcomes in patients with high-grade pT1 non–muscle-invasive bladder cancer (NMIBC). Materials and methods We retrospectively analysed clinical data and formalin-fixed paraffin-embedded (FFPE) tissues of 147 patients with primary high-grade pT1 NMIBC who underwent transurethral resection of the bladder. The stromal TIL density was scored as percentage of the stromal area infiltrated by mononuclear inflammatory cells over the total intratumoural stromal area. The main end-point was correlation with cancer-specific survival (CSS). Results Median follow-up was 8.2 years (6.1–9.5). Induction Bacillus Calmette–Guérin therapy was undergone by 126 patients (86%). Stromal TILs were high (≥10%) in 82 tumours (56%) and were positively associated with the tumour invasion depth (p = 0.01) and cancers with variant histology (p = 0.01). For the CSS analysis, high (≥10%) versus. low (<10%) stromal TIL hazard ratio (95% confidence interval) was 1.70 (0.7–3.9, p = 0.2). Conclusions A higher density of stromal TILs was associated with the tumour invasion depth in pT1 NMIBC. The level of TILs was not associated with survival outcomes. These data suggest that tumour aggressiveness is associated with an increased adaptive immune response in pT1 NMIBC. Characterisation of T-cell subtypes along with B-cells may be critical to enhance our knowledge of the host immune response in patients with high-risk NMIBC. Highlights • Lymphocytic infiltration significantly increases with tumour invasion depth in primary untreated pT1 bladder cancer. • A higher density of lymphocytic infiltration is not associated with better outcomes. • These data suggest that the antitumour immune response is different in high-grade pT1 non-NMIBC as opposed to numerous findings in MIBC. • Characterisation of T-cells and B-cells responses is critical to enhance our knowledge of antitumour immunity in patients with high-risk non-NMIBC. [ABSTRACT FROM AUTHOR]

Purpose: Over the past 3 decades, no major treatment breakthrough has been reported for advanced bladder cancer. Recent Food and Drug Administration (FDA) approval of five immune checkpoint inhibitors in the management of advanced bladder cancer represent new therapeutic opportunities. This review examines the available data of the clinical trials leading to the approval of ICIs in the management of metastatic bladder cancer and the ongoing trials in advanced and localized settings.Methods: A literature search was performed on PubMed and ClinicalTrials.gov combining the MeSH terms: ‘urothelial carcinoma’ OR ‘bladder cancer’, and ‘immunotherapy’ OR ‘CTLA-4’ OR ‘PD-1’ OR ‘PD-L1’ OR ‘atezolizumab’ OR ‘nivolumab’ OR ‘ipilimumab’ OR ‘pembrolizumab’ OR ‘avelumab’ OR ‘durvalumab’ OR ‘tremelimumab’. Prospectives studies evaluating anti-PD(L)1 and anti-CTLA-4 monoclonal antibodies were included.Results: Evidence-data related to early phase and phase III trials evaluating the 5 ICIs in the advanced urothelial carcinoma are detailed in this review. Anti-tumour activity of the 5 ICIs supporting the FDA approval in the second-line setting are reported. The activity of PD(L)1 inhibitors in the first-line setting in cisplatin-ineligible patients are also presented. Ongoing trials in earlier disease-states including non-muscle-invasive and muscle-invasive bladder cancer are discussed.Conclusions: Blocking the PD-1 negative immune receptor or its ligand, PD-L1, results in unprecedented rates of anti-tumour activity in patients with metastatic urothelial cancer. However, a large majority of patients do not respond to anti-PD(L)1 drugs monotherapy. Investigations exploring the potential value of predictive biomarkers, optimal combination and sequences are ongoing to improve such treatment strategies. [ABSTRACT FROM AUTHOR]