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Objectives: To assess the comparative effectiveness of robot-assisted radical cystectomy (RARC) with intracorporeal urinary diversion (ICUD) vs open radical cystectomy (ORC) for bladder cancer (BC)., Patients and Methods: We conducted a real-life monocentric study including all consecutive patients who underwent RARC with ICUD or ORC for BC at our institution from 2014 to 2023. Uni- and multivariable logistic and Cox regression analyses were used to compare perioperative, oncological and stricture outcomes between both groups by calculating odds (ORs) and hazard (HRs) ratios with their corresponding 95% confidence intervals (CIs), respectively., Results: Overall, 316 patients underwent either RARC with ICUD (n = 228 [72.2%]) or ORC (n = 88 [27.8%]). The perioperative benefits of RARC vs ORC included decreased risks of major blood loss (OR 0.10, 95% CI 0.04-0.23; P < 0.001), perioperative transfusion (OR 0.30, 95% CI 0.16-0.57; P < 0.001), 90-day major complications (OR 0.56, 95% CI 0.29-0.99; P = 0.04), and prolonged initial length of hospital stay (OR 0.20, 95% CI 0.09-0.35; P < 0.001), as well as more days alive and out of the hospital within 90 days of surgery (OR 2.56, 95% CI 1.46-4.6; P < 0.01). In addition, the use of RARC vs ORC was associated with a higher lymph node (LN) count (OR 3.35, 95% CI 1.83-6.30; P < 0.001), while there was no significant difference in recurrence-free (HR 0.72, 95% CI 0.49-1.07; P = 0.1), cancer-specific (HR 0.69, 95% CI 0.43-1.10; P = 0.1), overall (HR 0.76, 95% CI 0.47-1.20; P = 0.3) and uretero-ileal stricture-free (HR 1.18, 95% CI 0.62-2.25; P = 0.6) survival between both groups after a median (interquartile range) follow-up of 42.3 (16.4-73.8) months., Conclusion: Our real-world study supports the effectiveness of RARC with ICUD vs ORC for BC. We generally observed better perioperative outcomes, as well as similar oncological-except for higher LN count-and uretero-ileal stricture outcomes after RARC with ICUD vs ORC., (© 2024 The Author(s). BJU International published by John Wiley & Sons Ltd on behalf of BJU International.)

Objective: To assess the oncological outcomes of patients with high-risk (HR) and very high-risk (VHR) non-muscle-invasive bladder cancer (NMIBC) treated with upfront radical cystectomy (RC) vs Bacillus Calmette-Guérin (BCG) instillations from a contemporary European multicentre cohort., Patients and Methods: We conducted a retrospective analysis of 1491 patients diagnosed with HR- or VHR-NMIBC from a European multicentre database between 2015 and 2024. Patients were included if they received either upfront RC or at least five doses of BCG. A 1:1 propensity score matching (PSM) according to clinically relevant variables was applied. Progression was defined as muscle-invasive or metastatic disease. Cumulative incidence plots and multivariable competing risk regression models addressing cancer-specific mortality (CSM) were fitted., Results: Among the 1221 patients with HR- (n = 1221 [90%]) or VHR-NMIBC (n = 121 [10%]), 87 (7.1%) underwent upfront RC. The median follow-up was 2.6 years. After PSM (87 vs 87 patients), the 5-year CSM rate was similar in patients treated with BCG (13%) vs their upfront RC counterparts (16%) (hazard ratio: 1.77, 95% confidence interval [CI] 0.66-4.73; P = 0.3). Of the 1134 patients who initially received BCG, 73 (6.6%) eventually required delayed RC, with 34 (47%) progressing to muscle-invasive bladder cancer before delayed RC. The 3-year CSM rate was comparable in upfront RC (13%) vs delayed RC (11%) among non-progressing patients (P = 0.3). However, patients who progressed before delayed RC had worse 3-year CSM relative to those who did not (13% vs 31%, hazard ratio: 0.32, 95% CI 0.13-0.83; P = 0.018)., Conclusion: Within a European cohort of patients with HR- and VHR-NMIBC, upfront RC was rarely performed. Patients treated with BCG did not exhibit a CSM disadvantage relative to their upfront RC counterparts. After matching, long-term CSM was similar between BCG therapy and upfront RC. Delayed RC, led to worse outcomes if performed after progression, but matched upfront RC when performed before progression, underscoring importance of timely surgery., (© 2025 BJU International.)

Objective: To evaluate the oncological efficacy and safety of sequential intravesical gemcitabine/docetaxel (Gem/Doce) therapy in a European cohort of patients with high-risk and very-high-risk non-muscle-invasive bladder cancer (NMIBC) after previous Bacillus Calmette-Guérin (BCG) treatment., Materials and Methods: Data were retrospectively collected from 95 patients with NMIBC, treated with Gem/Doce at 12 European centres between 2021 and 2024. Patients previously treated with BCG who had completed a full induction course and received at least one follow-up evaluation were included. One-year disease-free survival (DFS), high-grade DFS and progression-free survival (PFS) were estimated using Kaplan-Meier curves. Adverse events (AEs) were recorded through medical interviews., Results: Of 75 patients, 63 (84%) were classified as having high-risk and 12 (16%) as having very-high-risk NMIBC. Over a median (interquartile range) follow-up of 9 (5-14) months, 20 patients (27%) relapsed and five (6.7%) underwent radical cystectomy. The 1-year DFS was 73% (95% confidence interval [CI] 62-86%), 1-year high-grade DFS was 79% (95% CI 68-91%) and 1-year PFS was 95% (95% CI 90-100%). AEs occurred in 34 patients (45%), with six (8.7%) experiencing severe AEs. Limitations of the study include the short follow-up and variability in both treatment dwelling times and dosage across centres., Conclusion: The intravesical Gem/Doce regimen demonstrated promising short-term oncological outcomes and was well tolerated in this cohort of patients with high- and very-high-risk NMIBC previously treated with BCG. Prospective studies and randomised trials are awaited to define the ideal candidates for Gem/Doce therapy and to standardise treatment protocols., (© 2025 BJU International.)

Objective: To investigate the influence of statins on the survival outcomes of patients with non-muscle-invasive bladder cancer (NMIBC) treated with adjuvant intravesical bacille Calmette-Guérin (BCG) immunotherapy., Patients and Methods: A retrospective cohort of consecutive patients with NMIBC who received intravesical BCG therapy from 2001 to 2020 and statins prescription were identified. Overall survival (OS), cancer-specific survival (CSS), recurrence-free survival (RFS), and progression-free survival (PFS) were analysed between the Statins Group vs No-Statins Group using Kaplan-Meier method and multivariable Cox regression., Results: A total of 2602 patients with NMIBC who received intravesical BCG were identified. The median follow-up was 11.0 years. On Kaplan-Meier analysis, the Statins Group had significant better OS (P < 0.001), CSS (P < 0.001), and PFS (P < 0.001). Subgroup analysis indicated statins treatment started before BCG treatment had better CSS (P = 0.02) and PFS (P < 0.01). Upon multivariable Cox regression analysis, the 'statins before BCG' group was an independent protective factor for OS (hazard ratio [HR] 0.607, 95% confidence interval [CI] 0.514-0.716), and CSS (HR 0.571, 95% CI 0.376-0.868), but not RFS (HR 0.885, 95% CI 0.736-1.065), and PFS (HR 0.689, 95% CI 0.469-1.013)., Conclusions: Statins treatment appears to offer protective effects on OS and CSS for patients with NMIBC receiving adjuvant intravesical BCG., (© 2024 BJU International.)

Objective: To perform a collaborative review of the literature exploring the microsatellite instability/deficient mismatch repair (MSI/dMMR) phenotype in patients with upper tract urothelial carcinoma (UTUC)., Method: A collaborative review of the literature available on Medline was conducted by the Cancer Committee of the French Association of Urology to report studies describing the genetic mechanisms, investigation, prevalence and impact of the MSI/dMMR phenotype in UTUC patients., Results: The predominant genetic mechanism leading to the MSI/dMMR phenotype in UTUC patients is related to the constitutional mutation of one allele of the MMR genes MLH1, MSH2, MSH6 and PMS2 within Lynch syndrome. Indications for its investigation currently remain limited to patients with a clinical suspicion for sporadic UTUC to refer only those with a positive testing for germline DNA sequencing to screen for this syndrome. With regard to technical aspects, despite the interest of MSIsensor, only PCR and immunohistochemistry are routinely used to somatically investigate the MSI and dMMR phenotypes, respectively. The prevalence of the MSI/dMMR phenotype in UTUC patients ranges from 1.7% to 57%, depending on the study population, investigation method and definition of a positive test. Younger age and a more balanced male to female ratio at initial diagnosis are the main specific clinical characteristics of UTUC patients with an MSI/dMMR phenotype. Despite the conflicting results available in the literature, these patients may have a better prognosis, potentially related to more favourable pathological features. Finally, they may also have lower sensitivity to chemotherapy but greater sensitivity to immunotherapy., Conclusion: Our collaborative review summarises the available data from published studies exploring the MSI/dMMR phenotype in UTUC patients, the majority of which are limited by a low level of evidence., (© 2024 The Authors. BJU International published by John Wiley & Sons Ltd on behalf of BJU International.)

Objective: To evaluate the impact of adjuvant therapy on oncological outcomes in patients with intermediate-risk non-muscle-invasive bladder cancer (NMIBC), as due to the poorly-defined and overlapping diagnostic criteria optimal decision-making remains challenging in these patients., Patients and Methods: In this multicentre study, patients treated with transurethral resection of bladder tumour for Ta disease were retrospectively analysed. All patients with low- or high-risk NMIBC were excluded from the analysis. Associations between adjuvant therapy administration with recurrence-free survival (RFS) and progression-free survival (PFS) rates were assessed in Cox regression models., Results: A total of 2206 patients with intermediate-risk NMIBC were included in the analysis. Among them, 1427 patients underwent adjuvant therapy, such as bacille Calmette-Guérin (n = 168), or chemotherapeutic agents, such as mitomycin C or epirubicin (n = 1259), in different regimens up to 1 year. The median (interquartile range) follow-up was 73.3 (38.4-106.9) months. The RFS at 1 and 5 years in patients treated with adjuvant therapy and those without were 72.6% vs 69.5% and 50.8% vs 41.3%, respectively. Adjuvant therapy was associated with better RFS (hazard ratio [HR] 0.79, 95% confidence interval [CI] 0.70-0.89, P < 0.001), but not with PFS (P = 0.09). In the subgroup of patients aged ≤70 years with primary, single Ta Grade 2 <3 cm tumours (n = 328), adjuvant therapy was not associated with RFS (HR 0.71, 95% CI 0.50-1.02, P = 0.06). While in the subgroup of patients with at least one risk factor including patient age >70 years, tumour multiplicity, recurrent tumour and tumour size ≥3 cm (n = 1878), adjuvant intravesical therapy was associated with improved RFS (HR 0.78, 95% CI 0.68-0.88, P < 0.001)., Conclusion: In our study, patients with intermediate-risk NMIBC benefit from adjuvant intravesical therapy in terms of RFS. However, in patients without risk factors, adjuvant intravesical therapy did not result in a clear reduction in the recurrence rate., (© 2024 The Authors. BJU International published by John Wiley & Sons Ltd on behalf of BJU International.)

Objective: To report the learning curve of multiple operators for fusion magnetic resonance imaging (MRI) targeted biopsy and to determine the number of cases needed to achieve proficiency., Materials and Methods: All adult males who underwent fusion MRI targeted biopsy between February 2012 and July 2021 for clinically suspected prostate cancer (PCa) in a single centre were included. Fusion transrectal MRI targeted biopsy was performed under local anaesthesia using the Koelis platform. Learning curves for segmentation of transrectal ultrasonography (TRUS) images and the overall MRI targeted biopsy procedure were estimated with locally weighted scatterplot smoothing by computing each operator's timestamps for consecutive procedures. Non-risk-adjusted cumulative sum (CUSUM) methods were used to create learning curves for clinically significant (i.e., International Society of Urological Pathology grade ≥ 2) PCa detection., Results: Overall, 1721 patients underwent MRI targeted biopsy in our centre during the study period. The median (interquartile range) times for TRUS segmentation and for the MRI targeted biopsy procedure were 4.5 (3.5, 6.0) min and 13.2 (10.6, 16.9) min, respectively. Among the 14 operators with experience of more than 50 cases, a plateau was reached after 40 cases for TRUS segmentation time and 50 cases for overall MRI targeted biopsy procedure time. CUSUM analysis showed that the learning curve for clinically significant PCa detection required 25 to 45 procedures to achieve clinical proficiency. Pain scores ranged between 0 and 1 for 84% of patients, and a plateau phase was reached after 20 to 100 cases., Conclusions: A minimum of 50 cases of MRI targeted biopsy are necessary to achieve clinical and technical proficiency and to reach reproducibility in terms of timing, clinically significant PCa detection, and pain., (© 2024 BJU International.)

Objective: To evaluate the prognostic value of programmed death ligand-1 (PD-L1) and programmed death-1 (PD-1) expression in patients with upper tract urothelial carcinoma (UTUC)., Patients and Methods: A retrospective multicentre study was conducted in 283 patients with UTUC treated with radical nephroureterectomy (RNU) between 2000 and 2015 at 10 French hospitals. Immunohistochemistry analyses were performed using 2 mm-core tissue microarrays with NAT105® and 28.8® antibodies at a 5% cut-off for positivity on tumour cells and tumour-infiltrating lymphocytes to evaluate PD-L1 and PD-1 expression, respectively. Multivariable Cox regression models were used to determine the independent predictors of recurrence-free (RFS), cancer-specific (CSS) and overall survival (OS)., Results: Overall, 63 (22.3%) and 220 (77.7%) patients with UTUC had PD-L1-positive and -negative disease, respectively, while 91 (32.2%) and 192 (67.8%) had PD-1-positive and -negative disease, respectively. Patients who expressed PD-L1 or PD-1 were more likely to have pathological tumour stage ≥pT2 (68.3% vs 49.5%, P = 0.009; and 69.2% vs 46.4%, P < 0.001, respectively) and high-grade (90.5% vs 70.0%, P = 0.001; and 91.2% vs 66.7%, P < 0.001, respectively) disease with lymphovascular invasion (52.4% vs 17.3%, P < 0.001; and 39.6% vs 18.2%, P < 0.001, respectively) as compared to those who did not. In multivariable Cox regression analysis adjusting for each other, PD-L1 and PD-1 expression were significantly associated with decreased RFS (hazard ratio [HR] 1.83, 95% confidence interval [CI] 1.09-3.08, P = 0.023; and HR 1.59, 95% CI 1.01-2.54, P = 0.049; respectively), CSS (HR 2.73, 95% CI 1.48-5.04, P = 0.001; and HR 1.96, 95% CI 1.12-3.45, P = 0.019; respectively) and OS (HR 2.08, 95% CI 1.23-3.53, P = 0.006; and HR 1.71, 95% CI 1.05-2.78, P = 0.031; respectively). In addition, multivariable Cox regression analyses evaluating the four-tier combination of PD-L1 and PD-1 expression showed that only PD-L1/PD-1-positive patients (n = 38 [13.4%]) had significantly decreased RFS (HR 3.07, 95% CI 1.70-5.52; P < 0.001), CSS (HR 5.23, 95% CI 2.62-10.43; P < 0.001) and OS (HR 3.82, 95% CI 2.13-6.85; P < 0.001) as compared to those with PD-L1/PD-1-negative disease (n = 167 [59.0%])., Conclusions: We observed that PD-L1 and PD-1 expression were both associated with adverse pathological features that translated into an independent and cumulative adverse prognostic value in UTUC patients treated with RNU., (© 2023 BJU International.)

Objectives: To assess the impact of pathological upstaging from clinically localized to locally advanced pT3a on survival in patients with renal cell carcinoma (RCC), as well as the oncological safety of various surgical approaches in this setting, and to develop a machine-learning-based, contemporary, clinically relevant model for individual preoperative prediction of pT3a upstaging., Materials and Methods: Clinical data from patients treated with either partial nephrectomy (PN) or radical nephrectomy (RN) for cT1/cT2a RCC from 2000 to 2019, included in the French multi-institutional kidney cancer database UroCCR, were retrospectively analysed. Seven machine-learning algorithms were applied to the cohort after a training/testing split to develop a predictive model for upstaging to pT3a. Survival curves for disease-free survival (DFS) and overall survival (OS) rates were compared between PN and RN after G-computation for pT3a tumours., Results: A total of 4395 patients were included, among whom 667 patients (15%, 337 PN and 330 RN) had a pT3a-upstaged RCC. The UroCCR-15 predictive model presented an area under the receiver-operating characteristic curve of 0.77. Survival analysis after adjustment for confounders showed no difference in DFS or OS for PN vs RN in pT3a tumours (DFS: hazard ratio [HR] 1.08, P = 0.7; OS: HR 1.03, P > 0.9)., Conclusions: Our study shows that machine-learning technology can play a useful role in the evaluation and prognosis of upstaged RCC. In the context of incidental upstaging, PN does not compromise oncological outcomes, even for large tumour sizes., (© 2023 The Authors. BJU International published by John Wiley & Sons Ltd on behalf of BJU International.)

Objectives: To determine the predictive and prognostic value of a panel of systemic inflammatory response (SIR) biomarkers relative to established clinicopathological variables in order to improve patient selection and facilitate more efficient delivery of peri-operative systemic therapy., Materials and Methods: The preoperative serum levels of a panel of SIR biomarkers, including albumin-globulin ratio, neutrophil-lymphocyte ratio, De Ritis ratio, monocyte-lymphocyte ratio and modified Glasgow prognostic score were assessed in 4199 patients treated with radical cystectomy for clinically non-metastatic urothelial carcinoma of the bladder. Patients were randomly divided into a training and a testing cohort. A machine-learning-based variable selection approach (least absolute shrinkage and selection operator regression) was used for the fitting of several multivariable predictive and prognostic models. The outcomes of interest included prediction of upstaging to carcinoma invading bladder muscle (MIBC), lymph node involvement, pT3/4 disease, cancer-specific survival (CSS) and recurrence-free survival (RFS). The discriminatory ability of each model was either quantified by area under the receiver-operating curves or by the C-index. After validation and calibration of each model, a nomogram was created and decision-curve analysis was used to evaluate the clinical net benefit., Results: For all outcome variables, at least one SIR biomarker was selected by the machine-learning process to be of high discriminative power during the fitting of the models. In the testing cohort, model performance evaluation for preoperative prediction of lymph node metastasis, ≥pT3 disease and upstaging to MIBC showed a 200-fold bootstrap-corrected area under the curve of 67.3%, 73% and 65.8%, respectively. For postoperative prognosis of CSS and RFS, a 200-fold bootstrap corrected C-index of 73.3% and 72.2%, respectively, was found. However, even the most predictive combinations of SIR biomarkers only marginally increased the discriminative ability of the respective model in comparison to established clinicopathological variables., Conclusion: While our machine-learning approach for fitting of the models with the highest discriminative ability incorporated several previously validated SIR biomarkers, these failed to improve the discriminative ability of the models to a clinically meaningful degree. While the prognostic and predictive value of such cheap and readily available biomarkers warrants further evaluation in the age of immunotherapy, additional novel biomarkers are still needed to improve risk stratification., (© 2021 The Authors BJU International published by John Wiley & Sons Ltd on behalf of BJU International.)

Objective: To identify single nucleotide polymorphisms (SNPs) associated with patterns of aggressiveness of non-muscle-invasive bladder cancer (NMIBC)., Patients and Methods: From January 2011 to December 2018, 476 patients with NMIBC were prospectively included. The first step aimed to identify SNPs associated with aggressiveness patterns (e.g. ≥pT1or high-grade/Grade 3 or presence of carcinoma in situ) by analysing the data of a genome-wide association study (GWAS) on 165 patients with BC. The second step aimed to validate the SNPs previously identified, by genotyping the germline DNA of 311 patients with NMIBC., Results: Overall, the median (interquartile range) age was 66 (58-75) years and the rate of patients with aggressive NMIBC was comparable between both groups (46% vs 46%, P = 1). GWAS data analysis identified four SNPs associated with an aggressive NMIBC (rs12615669, rs4976845, rs2989734, and rs2802288). In the validation cohort, the genotype CC of rs12615669, as well as age >70 years at the time of diagnosis were associated with aggressive NMIBC (P = 0.008 and P < 0.001, respectively). Genotyping of the entire cohort showed an association between aggressive NMIBC and the T allele of rs12615669 (P = 0.0007), the A allele of rs4976845 (P = 0.012), and the A allele of rs2989734 (P = 0.007). A significant association was also found for the entire cohort between the risk of progression and the A allele of rs4976845 (P = 0.04)., Conclusion: This two-phase study identified three SNPs (rs12615669, rs4976845, and rs2989734) associated with aggressive NMIBC and one SNP (rs4976845) associated with a higher risk of progression., (© 2020 The Authors BJU International © 2020 BJU International Published by John Wiley & Sons Ltd.)

Objective: To report the functional outcomes of robot-assisted laparoscopic artificial urinary sphincter (AUS; AMS 800™, American Medical Systems, Minnetonka, MN, USA) implantation and revision in women with stress urinary incontinence (SUI)., Patients and Methods: A pilot prospective monocentric study included all consecutive female patients with SUI and undergoing an AUS surgery (implantation or revision) using a robotic approach between 2012 and 2018. The AUS was implanted through a transperitoneal robotic approach. The dissection of the bladder neck was initiated using a posterior approach with a permanent visual control. Intraoperative and early postoperative complications were reported (Clavien-Dindo classification). Continence was defined as no pad usage., Results: A total of 41 patients, median (interquartile range [IQR]) age 67.5 (57-74.7) years were included. In the group of 27 patients undergoing an AUS implantation, one conversion to laparotomy, one bladder neck and one ureteric injury occurred. The AUS was not implanted in the two latest cases. Twelve minor (Clavien-Dindo Grade I-II) early postoperative complications occurring in 10 patients were reported. The median (IQR) follow-up was 19 (11-27) months. The continence rate was 84% (21/25 patients). In the group of 14 patients undergoing an AUS revision, no vaginal or bladder injury was reported. One patient had a bowel injury with conversion to laparotomy without AUS insertion. Two major (Clavien-Dindo Grade III-V) early postoperative complications occurred in two patients: one intraoperative bowel injury, which ultimately resulted in the death of the patient and one device infection requiring an explantation of the AUS. The median (IQR) follow-up was 18 (13.5-24.2) months. The continence rate was 83.3% (10/12 patients)., Conclusion: The results obtained after robot-assisted laparoscopic AUS implantation among women are promising despite the significant morbidity due to previous pelvic surgeries. Longer follow-up studies are needed., (© 2020 The Authors BJU International © 2020 BJU International Published by John Wiley & Sons Ltd.)

Objectives: To compare trends in the use of robot-assisted radical cystectomy (RARC) and changes over time in peri-operative outcomes in selected North American and European centres., Materials and Methods: We conducted a retrospective evaluation of 2401 patients treated with open radical cystectomy (ORC) or RARC for bladder cancer at 12 centres in North America and Europe between 2006 and 2018. We used the Kruskal-Wallis and chi-squared test to evaluate differences between continuous and categorical variables., Results: Overall, 49.5% of patients underwent RARC and 51.5% ORC. RARC became the most commonly performed procedure in contemporary patients, with an increase from 29% in 2006-2008 to 54% in 2015-2018 (P < 0.001). In the North American centres the use of RARC was higher than that of ORC from 2006, and remained stable over time, whereas in the European centres its use increased exponentially from 2% to 50%. In both groups patients who underwent RARC had less advanced T stages (P < 0.001), lower American Society of Anesthesiologists scores (P < 0.05), lower blood loss (P = 0.001) and shorter length of hospital stay (P < 0.05). No differences were found in early complications. Early readmission and re-operation rates were worse for patients treated with RARC in the European centres; however, when contemporary patients only were considered, the statistical significance was lost., Conclusion: The present study shows that the use of RARC has constantly increased since its introduction, overtaking ORC in the most contemporary series. While RARC was more frequently performed than ORC since its introduction in the North American centres and its use remained substantially stable over time, its use increased exponentially in the European centres. The different trends in use of RARC/ORC and changes over time in peri-operative outcomes between the North American and European centres can be attributed to the earlier introduction and spread of RARC in the former compared with the latter., (© 2019 The Authors BJU International © 2019 BJU International Published by John Wiley & Sons Ltd.)

The aim of the present review was to assess the prognostic impact of lymphovascular invasion (LVI) in transurethral resection (TUR) of bladder cancer (BCa) specimens on clinical outcomes. A systematic review and meta-analysis of the available literature from the past 10 years was performed using MEDLINE, EMBASE and Cochrane library in August 2017. The protocol for this systematic review was registered on PROSPERO (Central Registration Depository: CRD42018084876) and is available in full on the University of York website. Overall, 33 studies (including 6194 patients) evaluating the presence of LVI at TUR were retrieved. LVI was detected in 17.3% of TUR specimens. In 19 studies, including 2941 patients with ≤cT1 stage only, LVI was detected in 15% of specimens. In patients with ≤cT1 stage, LVI at TUR of the bladder tumour (TURBT) was a significant prognostic factor for disease recurrence (pooled hazard ratio [HR] 1.97, 95% CI: 1.47-2.62) and progression (pooled HR 2.95, 95% CI: 2.11-4.13), without heterogeneity (I 2 = 0.0%, P = 0.84 and I 2 = 0.0%, P = 0.93, respectively). For patients with cT1-2 disease, LVI was significantly associated with upstaging at time of radical cystectomy (pooled odds ratio 2.39, 95% CI: 1.45-3.96), with heterogeneity among studies (I 2 = 53.6%, P = 0.044). LVI at TURBT is a robust prognostic factor of disease recurrence and progression in non-muscle invasive BCa. Furthermore, LVI has a strong impact on upstaging in patients with organ-confined disease. The assessment of LVI should be standardized, reported, and considered for inclusion in the TNM classification system, helping clinicians in decision-making and patient counselling., (© 2018 The Authors BJU International published by John Wiley & Sons Ltd on behalf of BJU International.)

Objectives: To compare the prognostic value of the World Health Organization (WHO) 1973 and 2004 classification systems for grade in T1 bladder cancer (T1-BC), as both are currently recommended in international guidelines., Patients and Methods: Three uro-pathologists re-revised slides of 601 primary (first diagnosis) T1-BCs, initially managed conservatively (bacille Calmette-Guérin) in four hospitals. Grade was defined according to WHO1973 (Grade 1-3) and WHO2004 (low-grade [LG] and high-grade [HG]). This resulted in a lack of Grade 1 tumours, 188 (31%) Grade 2, and 413 (69%) Grade 3 tumours. There were 47 LG (8%) vs 554 (92%) HG tumours. We determined the prognostic value for progression-free survival (PFS) and cancer-specific survival (CSS) in Cox-regression models and corrected for age, sex, multiplicity, size and concomitant carcinoma in situ., Results: At a median follow-up of 5.9 years, 148 patients showed progression and 94 died from BC. The WHO1973 Grade 3 was negatively associated with PFS (hazard ratio [HR] 2.1) and CSS (HR 3.4), whilst WHO2004 grade was not prognostic. On multivariable analysis, WHO1973 grade was the only prognostic factor for progression (HR 2.0). Grade 3 tumours (HR 3.0), older age (HR 1.03) and tumour size >3 cm (HR 1.8) were all independently associated with worse CSS., Conclusion: The WHO1973 classification system for grade has strong prognostic value in T1-BC, compared to the WHO2004 system. Our present results suggest that WHO1973 grade cannot be replaced by the WHO2004 classification in non-muscle-invasive BC guidelines., (© 2018 The Authors BJU International © 2018 BJU International Published by John Wiley & Sons Ltd.)

Objective: To assess the impact of hospital volume (HV) and surgeon volume (SV) on perioperative outcomes of robot-assisted partial nephrectomy (RAPN)., Patients and Methods: All consecutive patients who underwent a RAPN from 2009 to 2015, at 11 institutions, were included in a retrospective study. To evaluate the impact of HV, we divided RAPN into four quartiles according to the caseload per year: low HV (<20/year), moderate HV (20-44/year), high HV (45-70/year), and very high HV (>70/year). The SV was also divided into four quartiles: low SV (<7/year), moderate SV (7-14/year), high SV (15-30/year), and very high SV (>30/year). The primary endpoint was the Trifecta defined as the following combination: no complications, warm ischaemia time (WIT) <25 min, and negative surgical margins., Results: In total, 1 222 RAPN were included. The mean (sd) caseload per hospital per year was 44.9 (26.7) RAPNs and the mean (sd) caseload per surgeon per year was 19.2 (14.9) RAPNs. The Trifecta achievement rate increased significantly with SV (69.9% vs 72.8% vs 73% vs 86.1%; P < 0.001) and HV (60.3% vs 72.3% vs 86.2% vs 82.4%; P < 0.001). The positive surgical margins (PSM) rate (P = 0.02), length of hospital stay (LOS; P < 0.001), WIT (P < 0.001), and operative time (P < 0.001), all decreased significantly with increasing SV. The PSM rate (P = 0.02), LOS (P < 0.001), WIT (P < 0.001), operative time (P < 0.001), and major complications rate (P = 0.01), all decreased significantly with increasing HV. In multivariate analysis adjusting for HV and SV (model 3), HV remained the main predictive factor of Trifecta achievement (odds ratio [OR] 3.70 for very high vs low HV; P < 0.001), whereas SV was not associated with Trifecta achievement (OR 1.58 for very high vs low SV; P = 0.34)., Conclusion: In this multicentre study HV and SV both greatly influenced RAPN perioperative outcomes, but HV appeared to have a greater impact than SV., (© 2018 The Authors BJU International © 2018 BJU International Published by John Wiley & Sons Ltd.)

Objective: To assess the association of survivin expression with clinicopathological features and biochemical recurrence (BCR) after radical prostatectomy (RP) in a large multi-institutional cohort., Methods: Survivin expression was evaluated by immunohistochemistry on a tissue microarray of RP cores from 3 117 patients. Survivin expression was considered altered when at least 10% of the tumour cells stained positive. The association of altered survivin expression with BCR was evaluated using Cox proportional hazards regression models., Results: Survivin expression was altered in 1 330 patients (42.6%). Altered expression was associated with higher Gleason score on RP (P = 0.001), extracapsular extension (P = 0.019), seminal vesicle invasion (P < 0.001) and lymph node metastases (P = 0.009). The median (interquartile range) follow-up was 38 (21-66) months. Patients with altered survivin expression had a shorter BCR-free survival time than those with normal expression (5-year BCR-free survival estimates: 74.7 vs 79.0%; P = 0.008). Altered survivin expression did not retain its prognostic value, however, after adjustment for the effect of established clinicopathological factors (P = 0.73). Subgroup analyses also showed no independent prognostic value of survivin., Conclusions: Survivin expression is commonly altered in patients undergoing RP. Altered survivin expression is associated with the clinicopathological features of biologically and clinically aggressive PCa. Survivin expression was associated with BCR only in univariable analysis, limiting its value in daily clinical decision-making., (© 2016 The Authors BJU International © 2016 BJU International Published by John Wiley & Sons Ltd.)

Objectives: To construct a nomogram based on preoperative variables to better predict the likelihood of complications occurring within 30 days of radical nephroureterectomy (RNU)., Patients and Methods: The charts of 731 patients undergoing RNU at eight academic medical centres between 2002 and 2014 were reviewed. Preoperative clinical, demographic and comorbidity indices were collected. Complications occurring within 30 days of surgery were graded using the modified Clavien-Dindo scale. Multivariate logistic regression determined the association between preoperative variables and post-RNU complications. A nomogram was created from the reduced multivariate model with internal validation using the bootstrapping technique with 200 repetitions., Results: A total of 408 men and 323 women with a median age of 70 years and a body mass index of 27 kg/m 2 were included. A total of 75% of the cohort was white, 18% had an Eastern Cooperative Oncology Group (ECOG) performance status ≥2, 20% had a Charlson comorbidity index (CCI) score >5 and 50% had baseline chronic kidney disease (CKD) ≥ stage III. Overall, 279 patients (38%) experienced a complication, including 61 events (22%) with Clavien grade ≥ III. A multivariate model identified five variables associated with complications, including patient age, race, ECOG performance status, CKD stage and CCI score. A preoperative nomogram incorporating these risk factors was constructed with an area under curve of 72.2%., Conclusions: Using standard preoperative variables from this multi-institutional RNU experience, we constructed and validated a nomogram for predicting peri-operative complications after RNU. Such information may permit more accurate risk stratification on an individual cases basis before major surgery., (© 2016 The Authors BJU International © 2016 BJU International Published by John Wiley & Sons Ltd.)

Objective: To validate Caveolin-1 as an independent prognostic marker of biochemical recurrence (BCR) in a large multi-institutional cohort of patients with prostate cancer treated with radical prostatectomy (RP)., Patients and Methods: Caveolin-1 expression was evaluated by immunochemistry on a tissue microarray in 3 117 patients treated with RP for prostate cancer at five institutions. Univariable and multivariable Cox proportional hazards regression models assessed the association of Caveolin-1 status with BCR. Harrell's c-index quantified prognostic accuracy., Results: Caveolin-1 was overexpressed in 644 (20.6%) patients and was associated with higher pathological Gleason sum (P = 0.002) and lymph node metastases (P = 0.05). Within a median (interquartile range) follow-up of 38 (21-66) months, 617 (19.8%) patients experienced BCR. Patients with overexpression of Caveolin-1 had worse BCR-free survival than those with normal expression (log-rank test, P = 0.004). Caveolin-1 was an independent predictor of BCR in multivariable analyses that adjusted for the effects of standard clinicopathological features (hazard ratio 1.21, P = 0.037). Addition of Caveolin-1 in a model for prediction of BCR based on these standard prognosticators did not significantly improve the predictive accuracy of the model. In subgroup analyses, Caveolin-1 was associated with BCR in patients with favourable pathological features (pT2pN0 and Gleason score = 6; P = 0.021)., Conclusions: We confirmed that overexpression of Caveolin-1 is associated with adverse pathological features in prostate cancer and independently predicts BCR after RP, especially in patients with favourable pathological features. However, it did not add prognostically relevant information to established predictors of BCR, limiting its use in clinical practice., (© 2015 The Authors BJU International © 2015 BJU International Published by John Wiley & Sons Ltd.)

Objective: To evaluate the effect of adjuvant chemotherapy (AC) on mortality after radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC) with positive lymph nodes (LNs) and to identify patient subgroups that are most likely to benefit from AC., Patients and Methods: We retrospectively analysed data of 263 patients with LN-positive UTUC, who underwent full surgical resection. In all, 107 patients (41%) received three to six cycles of AC, while 156 (59.3%) were treated with RNU alone. UTUC-related mortality was evaluated using competing-risks regression models., Results: In all patients (T(all) N+), administration of AC had no significant impact on UTUC-related mortality on univariable (P = 0.49) and multivariable (P = 0.11) analysis. Further stratified analyses showed that only N+ patients with pT3-4 disease benefited from AC. In this subgroup, AC reduced UTUC-related mortality by 34% (P = 0.019). The absolute difference in mortality was 10% after the first year and increased to 23% after 5 years. On multivariable analysis, administration of AC was associated with significantly reduced UTUC-related mortality (subhazard ratio 0.67, P = 0.022). Limitations of this study are the retrospective non-randomised design, selection bias, absence of a central pathological review and different AC protocols., Conclusions: AC seems to reduce mortality in patients with pT3-4 LN-positive UTUC after RNU. This subgroup of LN-positive patients could serve as target population for an AC prospective randomised trial., (© 2014 The Authors BJU International © 2014 BJU International Published by John Wiley & Sons Ltd.)

Objective: To evaluate long-term functional outcomes of artificial urinary sphincters (AUSs) and to determine how many men required explantation because of stress urinary incontinence (SUI) caused by sphincter deficiency after prostate surgery., Patients and Methods: Men who had undergone placement of an AUS (American Medical Systems AMS 800®) between 1984 and 1992 to relieve SUI caused by sphincter deficiency after prostate surgery were included. Continence, defined as no need for pads, was assessed at the end of the follow-up. Kaplan-Meier survival curves estimated the survival rate of the device without needing explantation or revision., Results: In all, 57 consecutive patients were included with a median (interquartile range, IQR) age of 69 (64-72) years. The median (IQR) duration of follow-up was 15 (8.25-19.75) years. At the end of follow-up, 25 patients (43.8%) still had their primary AUS. The AUS was explanted in nine men because of erosion (seven) and infection (two). Survival rates, without AUS explantation, were 87%, 87%, 80%, and 80% at 5, 10, 15, and 20 years, respectively. Survival rates, without AUS revision, were 59%, 28%, 15%, and 5% at 5, 10, 15, and 20 years, respectively. At the end of the follow-up, in intention-to-treat analysis, 77.2% of patients were continent., Conclusion: In the long term (>10 years) the AMS 800 can offer a high rate of continence to men with SUI caused by sphincter deficiency, with a tolerable rate of explantation and revision., (© 2014 The Authors. BJU International © 2014 BJU International.)

Objective: To compare outcomes of patients with lymph node (LN)-positive urothelial carcinoma of the bladder (UCB) treated with or without cisplatin-based combined adjuvant chemotherapy (AC) after radical cystectomy (RC)., Patients and Methods: We retrospectively analysed 1523 patients with LN-positive UCB, who underwent RC with bilateral pelvic LN dissection. All patients had no evidence of disease after RC. AC was administered within 3 months. Competing-risks models were applied to compare UCB-related mortality., Results: Of the 1523 patients, 874 (57.4%) received AC. The cumulative 1-, 2- and 5-year UCB-related mortality rates for all patients were 16%, 36% and 56%, respectively. Administration of AC was associated with an 18% relative reduction in the risk of UCB-related death (subhazard ratio 0.82, P = 0.005). The absolute reduction in mortality was 3.5% at 5 years. The positive effect of AC was detectable in patients aged ≤70 years, in women, in pT3-4 disease, and in those with a higher LN density and lymphovascular invasion. This study is limited by its retrospective and non-randomised design, selection bias, the absence of central pathological review and lack in standardisation of LN dissection and cisplatin-based protocols., Conclusion: AC seems to reduce UCB-related mortality in patients with LN-positive UCB after RC. Younger patients, women and those with high-risk features such as pT3-4 disease, a higher LN density and lymphovascular invasion appear to benefit most. Appropriately powered prospective randomised trials are necessary to confirm these findings., (© 2014 The Authors. BJU International © 2014 BJU International.)

Objective: To establish whether the expression of forkhead box protein P3 (Foxp3) provides specific diagnostic information about neurological patients with urothelial carcinoma of the bladder (UCB)., Patients and Methods: UCB tissue samples from neurological patients were retrieved and compared with control samples. The expression of Foxp3 was analysed via immunohistochemistry of microarray tissue sections. The correlation between Foxp3 expression, histological parameters and tumour stage was assessed., Results: Overall, 20 UCB tissue samples and 20 others without UCB from neurological patients, and 46 UCB tissue samples from non-neurological patients were analysed. The distribution of pT of UCB in the neurological patients was as follows: one low-grade pTa (5%), three high-grade pTa (15%), three pT1(15%), one pT2(5%), seven pT3(35%) and five pT4(25%). Squamous cell differentiation was seen in nine UCB samples (45%). Foxp3 expression was detected in tumour tissues, including one pTa high grade, one pT1, one pT2, five pT3 and five pT4 tumours. Foxp3 was expressed in 11/13 muscle-invasive tumours. All tumours displaying squamous cell differentiation expressed Foxp3. Foxp3 was not expressed in the pT3 tumours that displayed sarcomatoid and micropapillary properties. Among the bladder samples without UCB from neurological patients, no expression of Foxp3 was observed. Among the UCB samples from the non-neurological patients, only seven displayed squamous cell differentiation. All tumours that displayed squamous cell differentiation expressed Foxp3, including one pTa high grade, four pT3 and two pT4 tumours. Other tumours displaying urothelial differentiation did not express Foxp3. The expression of Foxp3 correlated to squamous cell differentiation in neurological (P = 0.004) and non-neurological UCB tissue (P < 0.001). In neurological, but not non-neurological UCB tissue, the expression of Foxp3 correlated with the muscle-invasive stage (P = 0.022)., Conclusions: Elevated expression of Foxp3 appears to be a characteristic of neurological patients presenting with aggressive UCB and squamous cell differentiation. Targeting Foxp3 may represent a novel strategy to improve anti-tumour immunotherapy for UCB., (© 2015 The Authors. BJU International © 2015 BJU International.)

Objectives: To assess the accuracy of magnetic resonance imaging (MRI)/transrectal ultrasonography (TRUS) fusion to guide first-round biopsies in the diagnosis of localised prostate cancer (PCa) in men with a prostate-specific antigen (PSA) ≤10 ng/mL., Patients and Methods: A prospective study was conducted on men who met the following criteria: first-round biopsy, multiparametric MRI (mpMRI) showing a lesion with a Likert score ≥2 and a PSA <10 ng/mL. All men underwent a extended 12-core protocol plus a protocol of two or three targeted cores on the mpMRI index lesion. The UroStation (Koelis, Grenoble, France) and a V10 ultrasound system with an end-fire three-dimensional TRUS transducer were used for the fusion imaging procedure. Significant PCa was defined as: at least one core with a Gleason score of 3 + 4 or 6 with a maximum cancer core length ≥4 mm., Results: A total of 152 men, whose median PSA level was 6 ng/mL, were included in the study. The proportion of positive cores was significantly higher with the targeted-core protocol than with the extended 12-core protocol (P < 0.001). The proportion of men with clinically significant PCa was higher with the targeted-core protocol than with the extended 12-core protocol (P = 0.03). The proportion of patients having at least one positive biopsy (targeted-core protocol) was significantly different among the Likert score categories (P < 0.001)., Conclusions: For the first round of biopsies, MRI/TRUS-fusion targeted biopsies detected more men with clinically significant PCa than did standard extended 12-core biopsy alone., (© 2014 The Authors. BJU International © 2014 BJU International.)

Objective: To propose and validate a nomogram to predict cancer-specific survival (CSS) after radical nephroureterectomy (RNU) in patients with pT1-3/N0-x upper tract urothelial carcinoma (UTUC)., Patients and Methods: The international and the French national collaborative groups on UTUC pooled data from 3387 patients treated with RNU. Only 2233 chemotherapy naïve pT1-3/N0-x patients were included in the present study. The population was randomly split into the development cohort (1563) and the external validation cohort (670). To build the nomogram, logistic regressions were used for univariable and multivariable analyses. Different models were generated. The most accurate model was assessed using Harrell's concordance index and decision curve analysis (DCA). Internal validation was then performed by bootstrapping. Finally, the nomogram was calibrated and externally validated in the external dataset., Results: Of the 1563 patients in the nomogram development cohort, 309 (19.7%) died during follow-up from UTUC. The actuarial CSS probability at 5 years was 75.7% (95% confidence interval [CI] 73.2-78.6%). DCA revealed that the use of the best model was associated with benefit gains relative to prediction of CSS. The optimised nomogram included only six variables associated with CSS in multivariable analysis: age (P < 0.001), pT stage (P < 0.001), grade (P < 0.02), location (P < 0.001), architecture (P < 0.001) and lymphovascular invasion (P < 0.001). The accuracy of the nomogram was 0.81 (95% CI, 0.78-0.85). Limitations included the retrospective study design and the lack of a central pathological review., Conclusion: An accurate postoperative nomogram was developed to predict CSS after RNU only in locally and/or locally advanced UTUC without metastasis, where the decision for adjuvant treatment is controversial but crucial for the oncological outcome., (© 2014 The Authors. BJU International © 2014 BJU International.)

Objective: To compare perioperative outcomes of early unclamping (EUC) vs standard unclamping (SUC) during robot-assisted partial nephrectomy (RAPN), as early unclamping of the renal pedicle has been reported to decrease warm ischaemia time (WIT) during laparoscopic PN., Patients and Methods: A retrospective multi-institutional study was conducted at eight French academic centres between 2009 and 2013. Patients who underwent RAPN for a renal mass were included in the study. Patients without vascular clamping or for whom the decision to perform a radical nephrectomy was taken before unclamping were excluded. Perioperative outcomes were compared using the chi-squared and Fisher's exact tests for discrete variables and the Mann-Whitney test for continuous variables. Predictors of WIT and estimated blood loss (EBL) were assessed using multiple linear regression analysis., Results: In all, there were 430 patients: 222 in the EUC group and 208 in the SUC group. Tumours were larger (35.8 vs 32.3 mm, P = 0.02) and more complex (R.E.N.A.L. nephrometry score 6.9 vs 6.1, P < 0.001) in the EUC group but surgeons were more experienced (>50 procedures 12.2% vs 1.4%, P < 0.001). The mean WIT was shorter (16.7 vs 22.3 min, P < 0.001) and EBL was higher (369.5 vs 240 mL, P = 0.001) in the EUC group with no significant difference in complications or transfusion rates. The results remained the same when analysing subgroups of complex renal tumours (R.E.N.A.L. nephrometry score ≥7) or RAPN performed by less experienced surgeons (<20 procedures). In multivariable analysis, EUC was predictive of decreased WIT (β -0.34; P < 0.001) but was not associated with EBL (β -0.09, P = 0.16)., Conclusions: EUC can reduce WIT during RAPN without increasing morbidity even for complex renal tumours or when being performed by less experienced surgeons., (© 2014 The Authors. BJU International © 2014 BJU International.)

Objective: To assess the prognostic role of extranodal extension (ENE) and the size of the largest lymph node (LN) metastasis in predicting early biochemical relapse (eBCR) in patients with LN metastasis after radical prostatectomy (RP)., Patients and Methods: We evaluated BCR-free survival in men with LN metastases after RP and pelvic LN dissection performed in six high-volume centres. Multivariable Cox regression tested the role of ENE and diameter of largest LN metastasis in predicting eBCR after adjusting for clinicopathological variables. We compared the discrimination of multivariable models including ENE, the size of largest LN metastasis and the number of positive LNs., Results: Overall, 484 patients were included. The median (interquartile range, IQR) follow-up was 16.1 (6-27.5) months. The median (IQR) number of removed LNs was 10 (4-14), and the median (IQR) number of positive LNs was 1 (1-2). ENE was present in 280 (58%) patients, and 211 (44%) had their largest metastasis >10 mm. Patients with ENE and/or largest metastasis of >10 mm had significantly worse eBCR-free survival (all P < 0.01). On multivariable analysis, number of positive LNs (≤2 vs >2) and the diameter of LN metastasis (≤10 vs >10 mm), but not ENE, were significant predictors of eBCR (all P < 0.003). ENE and diameter of LN metastasis increased the area under the curve of a baseline multivariable model (0.663) by 0.016 points., Conclusions: The diameter of the largest LN metastasis and the number of positive LNs are independent predictors of eBCR. Considered together, ENE and the diameter of the largest LN metastasis have less discrimination than the number of positive LNs., (© 2013 The Authors. BJU International © 2013 BJU International.)

The 'gold standard' treatment for patients with carcinoma invading the bladder muscle is radical cystectomy (RC). Such patients are known to be at risk of malnutrition because of age and disease factors. Current evidence has established the nutritional and immunological benefits of immune-enhancing nutritional supplements in upper gastrointestinal surgery. There are currently no guidelines for immunonutrition (IM) use in urology and bladder cancer specifically. We carried out a systematic review of the available literature in the MEDLINE/Embase database. We assessed the rates of malnutrition in RC cohorts and analysed the clinical impacts of nutritional deficiency. The impact of immune-enhancing supplements was also investigated in RC cohorts with regard to postoperative outcomes. The prevalence of severe malnutrition was found to be 16-22%. There was a consistent association of malnourished patients with adverse postoperative outcomes in terms of mortality and morbidity. There is a paucity of data regarding IM in urological cohorts. Postoperative IM in RC was not found to have significant benefits beyond early return to a normal diet. There is not enough evidence in malnourished urological study cohorts to establish a consensus on IM. Until there are more well-controlled comparative effective studies or randomized trials, the role of IM should be considered investigational in patients with bladder cancer., (© 2013 The Authors. BJU International © 2013 BJU International.)

Objective: To assess the impact of cigarette smoking status, cumulative smoking exposure, and time from cessation on intravesical recurrence (IVR) outcomes in patients treated with radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC)., Patients and Methods: In all, 519 patients underwent RNU at five institutions. Smoking history included smoking status, quantity of cigarettes smoked per day (cpd), duration, and time from cessation. The cumulative smoking exposure was categorised as light-short-term (≤19 cpd and ≤19.9 years), moderate (all combinations except light-short-term and heavy-long-term), and heavy-long-term (≥20 cpd and ≥20 years). Univariable/multivariable cox regression analyses assessed the effects of smoking on IVR., Results: In all, 190 patients (36%) never smoked; 205 (40%) and 125 (24%) were former and current smokers, respectively. Among smokers, 42 (8%), 185 (36%), and 102 (20%) patients were light-short-term, moderate, and heavy-long-term smokers, respectively. Within a median follow-up of 37 months, 152 patients (29%) had IVR. Actuarial IVR-free-survival estimates (standard error) at 2, 5, and 10 years were 72 (2)%, 58 (3)%, and 51 (4)%, respectively. In multivariable analyses, current smoking status, smoking intensity (≥20 cpd), smoking duration (≥20 years), and heavy-long-term smoking were associated with higher risk of IVR (all P ≤ 0.01). Patients who quit smoking ≥10 years before RNU had better IVR outcomes than current smokers and those patients who quit smoking <10 years before RNU., Conclusions: Cigarette smoking is significantly associated with IVR in patients treated with RNU for UTUC. Current and heavy-long-term smokers have the highest risk of IVR. Smoking cessation for >10 years before RNU seems to mitigate these detrimental effects., (© 2013 The Authors. BJU International © 2013 BJU International.)

Objectives: To evaluate the prognostic value of the Bajorin criteria in a multi-institutional cohort of patients with disease recurrence after radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC). To investigate whether clinical, pathological and/or biological factors at time of disease recurrence are also associated with cancer-specific outcomes in these patients., Patients and Methods: We identified 242 patients with disease recurrence after RNU for UTUC from 11 centres. With regard to the Bajorin criteria, patients were categorized into three groups based on two risk factors: Karnofsky performance status <80% and the presence of visceral metastasis. Assessed variables included pathological characteristics, time to disease recurrence, age-adjusted Charlson comorbidity index (ACCI), American Society of Anesthesiologists (ASA) score, and laboratory tests at time of disease recurrence., Results: Overall, 185 patients died from their disease; the median survival was 9 months. The survival rates at 1 year were 53, 33, and 39% for patients with no (n = 18), one (n = 109) and two (n = 115) risk factors, respectively, with no significant difference between the groups. In univariable analyses, higher pT-stage, tumour necrosis, non-administered salvage chemotherapy, higher ACCI score, higher ASA score, lower albumin level and higher white blood cell count were significantly associated with a shorter time to cancer-specific mortality., Conclusions: We confirmed the poor yet variable outcomes of patients with disease recurrence after RNU. While the Bajorin criteria seem to have limited prognostic value in this specific cohort, we found several other clinical variables to be associated with worse cancer-specific mortality. If validated, these factors should be taken into consideration for clinical trial design., (© 2013 The Authors. BJU International © 2013 BJU International.)

Objective: To assess the long-term outcomes obtained after artificial urinary sphincter (AUS) implantation in women with stress urinary incontinence (SUI)., Materials and Methods: Women with SUI caused by intrinsic sphincter deficiency who underwent an AUS placement between 1984 and 1992 were included. Explantation, revision and deactivation rates of the AUS were reported. Continence, defined as no pad use, was assessed at the end of the follow-up. Kaplan-Meier survival curves were generated to evaluate the survival rate of the device without explantation or revision., Results: A total of 34 patients were included. The median (interquartile range [IQR]) age of the patients at surgery was 56.5 (50-64.7) years and the median (IQR) follow-up was 17 (12-19) years. Overall, 26 women (74%) still had their AUS in place at the end of the follow-up, while eight patients underwent an explantation of the device. The 10-, 15- and 20-year device survival rates without explantation were 80, 80 and 74%, respectively. The 10-, 15- and 20-year survival rates of the device without revision were 79, 65 and 40%, respectively. After 20 years of follow-up, 11 women still had successful outcomes (61%)., Conclusion: The AUS provided satisfactory very long-term functional results among women with SUI caused by intrinsic sphincter deficiency., (© 2013 The Authors. BJU International © 2013 BJU International.)

Objective: To evaluate the impact of 'hereditary-like' status in upper tract urothelial carcinoma (UTUC) on the survival of patients who have undergone radical nephroureterectomy (RNU) and adjuvant chemotherapy., Patients and Methods: A multicentre retrospective study was performed on all patients with high-risk UTUC who underwent RNU and adjuvant cisplatin-based chemotherapy. Using a patient risk identification tool, we distinguished tumours suspected to be hereditary from sporadic tumours and compared survival rates., Results: A total of 112 patients with a median age of 67 years were included. Hereditary-like tumour status was detected in 35 patients (31.3%), while 77 patients (68.7%) had sporadic tumours. The median age was significantly younger in the hereditary-like tumour group (56.0 vs 69.8 years, P < 0.001). Overall survival (OS) after chemotherapy was significantly better in the group with hereditary-like tumours than in the group with sporadic tumours (5-year OS: 48.2 vs 32%; P = 0.008). The cancer-specific survival (CSS) rate was significantly better in the group with 'hereditary-like' tumours than in the group with sporadic tumours (5-year CSS: 58 vs 35%; P = 0.006). Although there was a trend in favour of the hereditary-like tumours, we observed no significant difference regarding progression-free survival (PFS) between the two groups (5-year PFS: 71 vs 52%; P = 0.07)., Conclusion: Adjuvant chemotherapy after RNU improves survival outcomes in patients with hereditary-like UTUC compared with those with sporadic tumours., (© 2013 The Authors. BJU International © 2013 BJU International.)

Objective: To determine the association between peri-operative blood transfusion (PBT) and oncological outcomes in a large multi-institutional cohort of patients undergoing radical cystectomy (RC) for urothelial carcinoma of the bladder (UCB)., Patients and Methods: We conducted a retrospective analysis of 2895 patients treated with RC for UCB. Univariable and multivariable Cox regression models were used to analyse the effect of PBT administration on disease recurrence, cancer-specific mortality, and any-cause mortality., Results: Patients' median (interquartile range [IQR]) age was 67 (60, 73) years and the median (IQR) follow-up was 36.1 (15, 84) months. Patients who received PBT were more likely to have advanced disease (P < 0.001), high grade tumours (P = 0.047) and nodal metastasis (P = 0.004). PBT was associated with a higher risk of disease recurrence (P = 0.003), cancer-specific mortality (P = 0.017), and any-cause mortality (P = 0.010) in univariable, but not multivariable, analyses (P > 0.05). In multivariable analyses, pathological tumour stage, pathological nodal stage, soft tissue surgical margin, lymphovascular invasion and administration of adjuvant chemotherapy were independent predictors of disease recurrence, cancer-specific mortality and any-cause mortality (all P values <0.002)., Conclusions: Patients with UCB who underwent RC and received PBT had a greater risk of disease recurrence, cancer-specific mortality and any-cause mortality in univariable, but not multivariable, analysis. Although the greater need for PBT with more advanced disease is probably caused by a number of factors, including surgical and cancer-related factors, the present analysis showed that the disease characteristics rather than need for PBT led to worse outcomes., (© 2013 The Authors. BJU International © 2013 BJU International.)

Objective: To describe for the first time the technique of robot-assisted artificial urinary sphincter (R-AUS) insertion in male patients with neurogenic incontinence., Materials and Methods: From January 2011 to the present date, six patients with spinal cord injury have undergone R-AUS insertion at our academic institution and we have prospectively collected data on pre-, peri- and early postoperative outcomes. A transperitoneal five-port approach was used using a three-arm standard da Vinci® robot (Intuitive Surgical, Sunnyvale, CA, USA) in a 30° reverse Trendelenburg position. The artificial urinary sphincter (AUS) cuff was placed circumferentially around the bladder neck, the reservoir was left intra-abdominally in a lateral vesicular space and the pump was placed in a classic scrotal position., Results: All six patients had successful robotic implantation of the AUS. The median patient age was 51.5 years, the median (range) operating time was 195 (175-250) min with no significant blood loss or intra-operative complications. The median (range) length of hospital stay was 4 (4-6) days. At a median (interquartile range) follow-up of 13 (6-21) months, all six patients had a functioning device with complete continence. To date, we have observed no incidence of early erosion, device infection or device malfunction., Conclusions: Allowing for the preliminary nature of our data, R-AUS insertion appears safe and technically feasible. Larger studies with long-term follow-up and comparison with open AUS insertion are necessary before definitive statements can be made for R-AUS in respect of complications and functional outcomes., (© 2013 BJU International.)

Objectives: To assess the impact of lymphovascular invasion (LVI) on upper urinary tract urothelial carcinomas (UTUCs) in a multicentre study on cancer-specific survival (CSS), recurrence-free survival and metastasis-free survival (MFS). To show the negative impact of LVI for patients with pN0/x disease and to stratify these patients into risk groups for metastatic relapse., Patients and Methods: A multicentre retrospective study was performed on patients who underwent radical nephroureterectomy between 1995 and 2010. LVI status was evaluated as a prognostic factor for survival using univariate and multivariate Cox regression analysis., Results: Overall, 551 patients were included and were divided into two groups: those without LVI (LVI-), n = 388 and those with LVI (LVI+), n = 163. LVI+ status was associated with high stage and grade UTUC and lymph node metastasis (P < 0.001). The 5-year CSS and MFS rates were significantly worse in the LVI+ group than in LVI- group (52.2 vs 84.5%, P < 0.001 and 43.8 vs 82.7%, P < 0.001, respectively). In multivariate analysis, LVI+ status was an independent prognostic factor for CSS and MFS (P = 0.04 and P < 0.001). These findings were confirmed for the pN0/x patient subgroup (n = 504, P < 0.001). In the pN0/x patient subgroup, we described a prognostic tool for MFS based on independent factors that permitted us to stratify patients into groups of high, intermediate or low risk of metastasis relapse., Conclusions: The presence of LVI was a strong predictor of a poor outcome for UTUC. When a lymphadenectomy has not been achieved, the report of LVI status is crucial to identfiy those patients at higher risk for metastatic relapse., (© 2013 BJU International.)

Objectives: To describe the most recent data from phase I and II clinical trials of stereotactic body radiation therapy (SBRT) using image-guided robotic radiosurgery, specifically the Cyberknife(®) (Accuracy Incorporated, Sunnyvale, CA, USA). To better determine thecurrent role of this type of radiosurgery in prostate cancer (PCa) management., Materials and Methods: Current clinical trials and relevant retrospective studies were identified from the literature, clinical trial databases, websites and conference abstracts. The indications, technical aspects, efficacy and toxicity of SBRT using the Cyberknife(®) system were summarized., Results: The Cyberknife(®) system is an experimental treatment mostly used for localized PCa in stage cT1/T2a-b N0 M0 with a Gleason score ≤ 7 and PSA level ≤ 20 ng/mL. Hypofractionated radiation therapy was delivered in five fractions of 7-7.25 Gy for a total dose of 35-36.25 Gy. After treatment, the median PSA levelfell from 4.9-8.3 ng/mL to 0.1-1.6 ng/mL at a median follow-up of 4-60 months. The biochemical progression-free survival rates ranged from 78.3 to 100%. Acute and late toxicities were mostly grade 1/2 rectal or urinary complications. Few grade 3 and no grade 4 toxicities occurred during follow-up; however, erectile dysfunction and testes toxicity were also reported., Conclusions: The use of the Cyberknife(®) system is limited mainly by its pretreatment and maintenance costs. Despite encouraging preliminary results, longer-term follow-up and randomized controlled phase III clinical trials are necessary before the Cyberknife(®) system becomes a standard treatment method., (© 2013 BJU International.)

Objective: To prospectively compare the surgical and pathological outcomes obtained with robot-assisted laparoscopic partial nephrectomy (RAPN) or laparoscopic PN (LPN) for renal cell carcinoma in a multicentre cohort., Patients and Methods: Between 2007 and 2011, 265 nephron-sparing surgeries were performed at six French urology departments. The patients underwent either RAPN (n = 220) or LPN (n = 45) procedures. The operative data included operative duration, warm ischaemia time (WIT) and estimated blood loss (EBL). The postoperative outcomes included length of stay (LOS), creatinine variation (Modification of Diet in Renal Disease group), Clavien complications and pathological results. The complexity of the renal tumour was classified using the R.E.N.A.L. nephrometry scoring system. Student's t-test and chi-squared tests were used to compare variables., Results: The median follow-ups for the RAPN and LPN groups were 7 and 18 months, respectively (P < 0.001). Age and American Society of Anesthesiology score were significantly higher in the LPN group (P = 0.02 and P = 0.004, respectively). These variables were lower in the RAPN group: WIT [mean (sd) 20.4 (9.7) vs 24.3 (15.2) min; P = 0.03], operative duration [mean (sd) 168.1 (55.5) vs 199.7 (51.2) min; P < 0.001], operating room occupation time [mean (sd) 248.3 (66.7) vs 278.2 (71.3) min; P = 0.008], EBL [mean (sd) 244.8 (365.4) vs 268.3 (244.9) mL; P = 0.01], use of haemostatic agents [used in 78% of RAPNs and 100% of LPNs; P < 0.001] and LOS [mean (sd) 5.5 (4.3) vs 6.8 (3.2) days; P = 0.05). There were no significant differences between pre- and postoperative creatinine levels, pathology report or complication rates between the groups. The main limitation was due to the study's non-randomised design., Conclusion: RAPN is not inferior to pure LPN for perioperative outcomes (i.e. EBL, operative duration, WIT, LOS). Only a randomised study with a longer follow-up can now provide further insight into oncological outcomes., (© 2012 BJU International.)

Unlabelled: What's known on the subject? and What does the study add? Hereditary non-polyposis colorectal cancer (HNPCC), also known as Lynch syndrome, is an autosomal dominant multi-organ cancer syndrome. Upper urinary tract urothelial carcinomas belong to HNPCC-related tumours and rank third within this group after colorectal and endometrial cancer. However, many urologists are not aware of this association and it is presumed that some hereditary cancers are misclassified as sporadic and that their incidence is underestimated. Consequently, family members of patients with upper urinary tract urothelial carcinomas secondary to HNPCC may be denied appropriate surveillance and early detection. A significant proportion of patients (21.3%) with newly diagnosed upper urinary tract urothelial carcinomas may have underlying HNPCC. Demographic and epidemiological characteristics suggest different mechanisms of carcinogenesis among this population. Recognition of such potential is essential for appropriate clinical and genetic management of patients and family. In order to help to identify these patients, we propose a patient-specific checklist., Objective: • To identify, based on previously described clinical criteria, hereditary upper urinary tract urothelial carcinomas (UUT-UCs) that are likely to be misclassified as sporadic although they may belong to the spectrum of hereditary non-polyposis colorectal cancer (HNPCC) associated cancers., Patients and Methods: • We identified, using established clinical criteria, suspected hereditary UUT-UC among 1122 patients included in the French national database for UUT-UC. • Patients were considered at risk for hereditary status in the following situations: age at diagnosis <60 years with no previous history of bladder cancer; previous history of HNPCC-related cancer regardless of age; one first-degree relative with HNPCC-related cancer diagnosed before 50 years of age or two first-degree relatives diagnosed regardless of age., Results: • Overall, 239 patients (21.3%) were considered to be at risk of hereditary UUT-UC. • Compared with sporadic cases, hereditary cases are more likely to be female (P= 0.047) with less exposure to tobacco (P= 0.012) and occupational carcinogens (P= 0.037). A greater proportion of tumours were located in the renal pelvis (54.5% vs 48.4%; P= 0.026) and were lower grade (40% vs 30.1%; P= 0.015) in the hereditary cohort. • The overall, cancer-specific and recurrence-free survival rates were similar in both cohorts. • We propose a patient-specific risk identification tool., Conclusions: • A significant proportion (21.3%) of patients with newly diagnosed UUT-UC may have underlying HNPCC as a cause. • Recognition of such potential and application of a patient-specific checklist upon diagnosis will allow identification and appropriate clinical and genetic management for patient and family., (© 2012 BJU INTERNATIONAL.)

Unlabelled: Study Type--Prognosis (cohort) Level of Evidence 2b. What's known on the subject? and What does the study add? Upper urinary tract urothelial carcinoma (UUT-UC) is a rare disease, usually treated by nephroureterectomy, occurring in a population with a median age of 70 years and with frequent tobacco use and other comorbidities. We know that the American Society of Anesthesiologists (ASA) score has prognostic value in urological oncology but this has not been assessed in UUT-UC. Using a multi-institutional French database, we have shown that the 5-year cancer-specific survival differed significantly between ASA 1, ASA 2 and ASA 3 patients (83.8%, 76.9% and 70.6%, respectively; P = 0.01). ASA status had a significant impact on cancer-specific survival in univariate and multivariate analyses, with a threefold higher risk of mortality at 5 years for ASA 3 compared with ASA 1 patients (P = 0.04)., Objective: • To evaluate the impact of American Society of Anesthesiologists (ASA) scores on the survival of patients treated with radical nephroureterectomy (RNU) for upper urinary tract urothelial carcinoma (UUT-UC)., Patients and Methods: • A retrospective multi-institutional cohort study of the French collaborative national database of UUT-UC treated by RNU in 20 centres from 1995 to 2010. • The influence of age, gender and ASA score on survival was assessed using a univariable and multivariable Cox regression analysis with pathological features used as covariables., Results: • Overall, 554 patients were included. The median follow-up was 26 months (10-48 months), and the median age was 69.5 years (61-76 years). In total, 114 (20.6%) patients were classified as ASA 1, 326 (58.8%) as ASA 2 and 114 (20.6%) as ASA 3. • The 5-year recurrence-free survival (P = 0.21) and metastasis-free survival (P = 0.22) were not significantly different between ASA 1 (52.8% and 76%), ASA 2 (51.9% and 75.3%) and ASA 3 patients (44.1% and 68.2%, respectively). • The 5-year cancer-specific survival differed significantly between ASA 1, ASA 2 and ASA 3 patients (83.8%, 76.9% and 70.6%, respectively; P = 0.01). • ASA status had a significant impact on cancer-specific survival in univariate and multivariate analyses, with a threefold higher risk of mortality at 5 years for ASA 3 compared with ASA 1 patients (P = 0.04)., Conclusions: • ASA classification correlates significantly with cancer-specific survival after RNU for UUT-UC. • It is a further pre-operative clinical variable that can be incorporated into future risk prediction tools for UUT-UC to improve their accuracy., (© 2012 BJU INTERNATIONAL.)

What's known on the subject? and What does the study add? Diethylstilbestrol (DES) has been found to have anti-tumour properties and clinical effectiveness in prostate cancer that is resistant to the first-line hormonal therapy. This review found that low-dose DES has anti-tumour efficacy with limited cardiovascular side effects and should be considered for secondary hormone manoeuvres. The aim of this review was to describe the most recent data from contemporary clinical trials of diethylstilbestrol (DES) to better determine its current role in advanced prostate cancer treatment as new hormonal therapies emerge. Relevant clinical studies using 1 mg of DES in castrate-resistant prostate cancer (CRPC) were identified from the literature, clinical trial databases, websites and conference abstracts. The efficacy and safety outcomes were summarized. DES in CRPC produced a biological response (change in PSA level) and improved the median survival of patients when used as a second-line hormone therapy after standard androgen deprivation with bicalutamide and LHRH analogues. These findings were for low doses of DES. The 1-mg dose is associated with a reduced toxicity, including fewer thromboembolic and cardiovascular events. Low-dose DES appears to be safe and effective for CRPC before initiating chemotherapy. The cost/efficiency ratio may encourage physicians to consider DES as a therapy option before chemotherapy in non-symptomatic CRPC., (© 2012 THE AUTHORS. BJU INTERNATIONAL © 2012 BJU INTERNATIONAL.)

Unlabelled: What's known on the subject? and What does the study add? Upper urinary tract urothelial carcinomas (UUT-UCs) are rare tumours. Because of the aggressive pattern of UC, radical nephroureterectomy (RNU) with bladder cuff removal remains the 'gold-standard' treatment. However, conservative strategies, such as segmental ureterectomy (SU) or endourological management, have also been developed in patients with imperative indications. Some teams are now advocating the use of conservative management more commonly in cases of elective indications of UUT-UCs. Due to the paucity of cases of UUT-UC, only limited data are available on the oncological outcomes afforded by conservative management. We retrospectively investigated the oncological outcomes after SU and RNU in a large multi-institutional database. Overall, 52 patients were treated with SU and 416 with RNU. There was no statistical difference between the RNU and SU groups for the 5-year probability of cancer-specific survival, recurrence-free survival and metastasis-free survival. The type of surgery was not a significant prognostic factor in univariate analysis. The results were the same in a subgroup analysis of only unifocal tumours of the distal ureter with a diameter of <2 cm and of low stage (≤T2). Our results suggest that oncological outcomes after conservative treatment with SU are comparable to RNU for the management of UUT-UC in select cases., Objective: To compare recurrence-free survival (RFS), metastasis-free survival (MFS) and cancer-specific survival (CSS) after segmental ureterectomy (SU) vs radical nephroureterectomy (RNU) for urothelial carcinoma (UC) of the upper urinary tract (UUT-UC) located in the ureter., Patients and Methods: We performed a multi-institutional retrospective review of patients with UUT-UC who had undergone RNU or SU between 1995 and 2010. Type of surgery, Tumour-Node-Metastasis status, tumour grade, lymphovascular invasion and positive surgical margin were tested as prognostic factors for survival., Results: In all, 52 patients were treated with SU and 416 with RNU. The median (range) follow-up was 26 (10-48) months. The 5-year probability of CSS, RFS and MFS for SU and RNU were 87.9% and 86.3%, respectively (P = 0.99); 37% and 47.9%, respectively (P = 0.48); 81.9% and 85.4%, respectively (P = 0.51). In univariable analysis, type of surgery (SU vs RNU) failed to affect CSS, RFS and MFS (P = 0.94, 0.42 and 0.53, respectively). In multivariable analyses, pT stage and pN stage achieved independent predictor status for CSS (P = 0.005 and 0.007, respectively); the positive surgical margin and pT stage were independent prognostic factors of RFS and MFS (P = 0.001, 0.04, 0.009 and 0.001, respectively). The main limitation of the study is its retrospective design, which is due to the rarity of the disease., Conclusions: Short-term oncological outcomes after conservative treatment with SU are comparable to RNU for the management of UUT-UC in select cases and should be considered an option. In every other case, RNU still represents the 'gold standard' for the treatment of UUT-UC., (© 2012 BJU INTERNATIONAL.)

Unlabelled: What's known on the subject? and What does the study add? Urinary incontinence is one of the major drawbacks of radical prostatectomy, regardless of the procedure used (i.e. open, laparoscopic or robotic-assisted). Several technical modifications have been described to improve postoperative continence, highlighting the role of puboprostatic ligaments and posterior reconstruction of the rhabdomyosphincter. The results obtained are inconsistent when applied to robotic surgery. The present multicentre randomized study shows that anterior suspension combined with posterior reconstruction is a safe and easy-to-perform technique for improving early continence after robotic-assisted laparoscopic prostatectomy., Objective: To assess the impact on urinary continence of anterior retropubic suspension with posterior reconstruction during robot-assisted laparoscopic prostatectomy (RALP)., Patients and Methods: In total, 72 patients who were due to undergo prostatectomy between July 2009 and July 2010 were prospectively randomized into two groups: group A underwent a standard RALP procedure and group B had anterior suspension and posterior reconstruction during RALP. The primary outcome measure was urinary continence, assessed using the University of California Los Angeles Prostate Cancer Index questionnaire at 15 days, and at 1, 3 and 6 months, after surgery. Other data recorded were operation duration, blood loss, length of hospital stay, duration of bladder catheterization, complications and positive margin rate., Results: The continence rates at 15 days, and at 1, 3 and 6 months, after surgery were 3.6%, 7.1%, 15.4% and 57.9%, respectively, in group A, and 5.9%, 26.5%, 45.2% and 65.4%, respectively, in group B. The continence rates differed statistically between groups at 1 and 3 months (P = 0.047 and P = 0.016, respectively). There was no significant difference between groups regarding complications (P = 0.8) or positive margin rate (P = 0.46)., Conclusion: Anterior suspension associated with posterior reconstruction during RALP improved the early return of continence, without increasing complications., (© 2012 BJU INTERNATIONAL.)

What's known on the subject? and What does the study add? Sporadic clear cell Renal Cell Carcinoma (ccRCC) is dominated by nutations of the VHL gene located on chromosome 3p in up to 90% of cases. This gene plays a critical role in hypoxia response, including stimulation of neoangiogenesis. Since 2006, anti-angiogenci therapies targeting this pathway are used in metastatic patients with objective response rate as high as 45%. However, these treatments don't target directly the tumour cell, allowing the potential for disease progession despite treatment. Large scale analysis recently showed that substantial genetic heterogeneity exists in ccRCC. Associated alterations include genes implicated in methylation regulation in 15% of cases, underlying the importance of epigenetic modifications, and truncating mutations in chromatin remodelling complex PRMB1 in 41% of cases. Systematic screening of these tumours is a way to fully determine the somatic genetic architecture of RCC in order to improve tumour classification, to develop prognostic and predictive markers and to target new molecular pathways involved in carcinogenesis. • A critical review is provided of the recent progress in oncogenetics applied to renal cell carcinoma (RCC) by highlighting our current understanding of the genetic pathways involved in carcinogenesis and its current and future clinical application. • RCC comprises a model of translational research because an improved understanding of molecular pathways has led to several targeted therapy options for patients with metastatic RCC. • Alteration of the product of the Von Hippel-Lindau gene/hypoxia inductible factor/vascular endothelial growth factor pathway is well characterized in carcinogenesis and is the target of the current therapies for metastatic RCC. • However, substantial genetic heterogeneity exists in this cancer and current treatments do not target directly the tumour cell. • Improving overall survival still remains a challenging objective but, currently, there is a lack of prognostic and predictive biomarkers for response to treatment. • Further information is awaited from the genomic approach to tumour classification, prognostic markers and predictive indicators of response to the treatment, as well as the personal susceptibility of developing RCC when exposed to risk factors. • Recent technological developments, such as large-scale analysis and high-speed sequencing, will allow the systematic screening of tumours to fully determine the somatic genetic architecture of RCC., (© 2011 THE AUTHORS. BJU INTERNATIONAL © 2011 BJU INTERNATIONAL.)

Objective: To evaluate based on the best available data whether there is a contemporary role for percutaneous needle biopsy in the era of small renal masses., Patients and Methods: SRMs are acknowledged to be tumours less than 4cm and account for 48%-66% of new kidney cancers. Renal mass biopsy (RMB), traditionally limited to specific clinical scenarios and with inherent diagnostic accuracy problems has increased in popularity in recent years and is a potential valuable tool in the assessment of SRMs. Our discussion focuses on these issues. We performed a thorough Medline literature review using a combination of the following keywords; small renal mass, renal biopsy, percutaneous renal biopsy, renal mass biopsy and renal cell carcinoma. We identified the seminal articles with data/information pertaining to renal mass biopsy in small renal masses., Results: The facts that 1) a significant number of SRMs are diagnosed in an elderly patient cohort, 2) 20% of SRMs are benign on formal histology, 3) there are various management strategies now available and 4) modern RMB has a diagnostic accuracy >90% with few complications, are all reasons why there has been renewed interest in RMB., Conclusion:   There is a contemporary role for RMB in the era of SRM as the incorporation of molecular profiling of tissue from RMB would augment our ability to risk stratify SRMs on an individual patient basis and adopt management accordingly. However, clinical judgement is paramount as there remains an unpredictable non-negligible risk of disease progression and metastasis whilst on surveillance., (© 2011 THE AUTHORS. BJU INTERNATIONAL © 2011 BJU INTERNATIONAL.)

Objectives: •  To discuss how the development of new generation flexible ureterorenoscopes in combination with photodynamic diagnosis (PDD) improves the assessment of urothelial cell carcinoma of the upper urinary tract (UUT-UCC). •  Ultimately, this may allow accurate tumour classification and the ability to select which patients would benefit from conservative treatment as opposed to radical surgery., Materials and Methods: •  We conducted an exhaustive Pubmed literature search using a combination of keywords including: ureterorenoscopy, UUT-UCC diagnosis, PDD, narrow band imaging, conservative treatment UUT-UCC and molecular urinalysis. •  We then selected salient high calibre articles relevant to our objective., Results: •  We give specific consideration to anatomical aspects of UUT-UCC investigation, PDD in UCC, aminolevulinic acid and its derivatives, autofluorescence, narrow band imaging, molecular marker analysis and the recent advances in ureterorenoscopic technology. •  The traditional pitfalls of UUT-UCC diagnosis, namely poor visualisation and difficulty in obtaining representative histological samples, are being circumvented by the introduction of modern digital flexible ureteroscopes that can be combined with PDD and molecular analysis to improve tumour classification, deferring to conservative treatment accordingly., Conclusion: •  The accuracy of the diagnostic work-up of UUT-UCC is improving due to advances in technology, pharmaceutical agents and incorporation of molecular markers, all factors allowing us to characterise tumours of the UUT more definitively., (© 2011 THE AUTHORS. BJU INTERNATIONAL © 2011 BJU INTERNATIONAL.)

Study Type - Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? The resection of the distal ureter and its orifice is an oncological principle during radical nephroureterectomy which is based on the fact that it represents a part of the urinary tract exposed to a considerable risk of recurrence. After removal of the proximal part it is hardly possible to image or approach it by endoscopy during follow-up. Recent publications on survival after nephroureterectomy do not allow the conclusion that removal of distal ureter and bladder cuff are useless. Several techniques of distal ureter removal have been described but they are not equivalent in term of oncological safety. • The standard treatment of upper urinary tract urothelial carcinomas (UUT-UCs) must obey oncological principles, which consist of a complete en bloc resection of the kidney and the ureter, as well as excision of a bladder cuff to avoid tumour seeding. • The open technique is the 'gold standard' of treatment to which all other techniques developed are necessarily compared, and various surgical procedures have been described. • The laparoscopic stapling technique maintains a closed system but risks leaving behind the ureteric and bladder cuff segments. • Transvesical laparoscopic detachment and ligation is a valid approach from an oncological stance but is technically difficult. The major inconvenience of the transurethral resection of the ureteric orifice and intussusception techniques is the potential for tumour seeding. • Management of the distal ureter via the robot-assisted laparoscopic method is technically feasible, but outcomes from these procedures are still preliminary. • Therefore, prospective comparative studies with more thorough explorations of these techniques are needed to solve the dilemma of the management of the distal ureter during nephroureterectomy. However, bladder cuff excision should remain the standard of care irrespective of the stage of the disease., (© 2010 THE AUTHORS. BJU INTERNATIONAL © 2010 BJU INTERNATIONAL.)

According to the literature, the current preferred treatment for T3 prostate cancer is a combination of radiotherapy and extended hormone therapy. The preoperative staging based on digital rectal examination results alone now appears obsolete from the investigated series, in which 20% of T3 prostate cancer is over-staged during physical examination. Prostatic magnetic resonance imaging is becoming increasingly necessary to evaluate extraprostatic extension during the preoperative evaluation. European Association of Urology guidelines recommend the use of radical prostatectomy only in selected patients with cT3a who have a PSA <20 ng/mL and a biopsy Gleason score ≤8. The cancer control obtained after the implementation of radical prostatectomy is variable from one series to another, with PSA-free survival rates at 5, 10 and 15 years ranging from 45 to 62%, 43 to 51% and 15 to 49%, respectively. The specific survival rates at 5, 10 and 15 years are between 84 and 98%, 84 and 91% and 76 and 84%, respectively. The surgical margins rate varies from 22% to 61% depending on the specific operative technique used and the surgeon's own experience level. Regarding urinary continence, functional outcomes are in line with those of prostatectomy for localized prostate cancer. Upon consideration of erectile dysfunction, the rates are linked with the type of surgery performed, which can at times be fairly extensive. There is no impact on the overall or specific survival rate of neoadjuvant treatments. One of the problems currently depends on the efficacy of early adjuvant treatment after prostatectomy, especially regarding the use of adjuvant external beam radiotherapy. Radical prostatectomy can be considered in selected cases as a viable alternative to the first-line treatment option. However, patients must be counselled that they may undergo complementary treatments during the postoperative course of the disease., (© 2010 THE AUTHORS. JOURNAL COMPILATION © 2010 BJU INTERNATIONAL.)

Although the accepted standard upon failing intravesical bacille Calmette-Guérin (BCG) in patients with high-risk non-muscle-invasive bladder cancer (NMIBC) is radical cystectomy, there are some patients for whom this is not an option. We critically reviewed previous reports on the treatment possibilities available in such a clinical scenario. The options available can be categorized as chemotherapy, immunotherapy, device-assisted therapy and combined therapy. Combining new with established intravesical treatments seems to hold the most promise. Maintenance thermo-chemotherapy gives a reported 2-year disease-free survival rate of 50% and in small early-phase studies of intravesical gemcitabine administered in combination with mitomycin-C, tolerance and efficacy data would suggest the need for larger trials, given the early encouraging results. Electromotive mitomycin-C given sequentially with BCG might not only reduce the recurrence rate but also reduce progression and disease-specific mortality, although currently there is no trial in a specific population with 'BCG failure'.

Prostate cancer is the most common malignancy of the urogenital tract. Although controversial, prostate-specific antigen (PSA) testing is widely used for screening and follow-up of prostate cancer, but because of its limited specificity and sensitivity, PSA is not an ideal test. We currently lack the necessary tools to differentiate between latent disease with little likelihood of clinical manifestation and aggressive tumours that are likely to metastasize and lead to potentially lethal disease. DNA methylation is an important epigenetic mechanism of gene regulation and plays essential roles in tumour initiation and progression. Currently, aberrant promoter hypermethylation has been investigated in specific genes from the following groups: tumour-suppressor genes, proto-oncogenes, genes involved in cell adhesion, and genes involved in cell-cycle regulation. Glutathione S-transferase P1 (GSTP1) has been shown to be a biomarker for prostate cancer. Other genes, e.g. CD44, PTGS2, E-cadherin, CDH13, and cyclin D2 have been found to be prognostic markers for prostate cancer. In cell samples derived from the urine, the presence of the hypermethylation of either GSTP1 or RASS1a has been shown to be both sensitive and specific for detecting prostate cancer. Several studies have found that analysis of hypermethylation using a panel of tumour-suppressor genes yielded better results for detecting prostate cancer than the analysis of single-gene methylation. Hence, these different panels (e.g. GSTP1, APC, PTGS2, T1G1 and EDNRB) are of interest for detecting prostate cancer. Also, the methylation profile of multiple regulatory genes might be altered at the time of cancer relapse. Thus, preliminary results on the use of the methylation status of specific genes as potential tumour biomarkers for the early diagnosis and the risk stratification of patients with prostate cancer are promising.