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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 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.)

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.)

Objective: To investigate the feasibility, efficacy, and safety of trimodal therapy (TMT) using a bifractionated split-course hypofractionated radiotherapy (RT) for non-metastatic muscle-invasive bladder cancer (MIBC) in elderly patients., Patients and Methods: We retrospectively reviewed the characteristics and outcomes of patients aged >75 years with non-metastatic MIBC suitable or not for radical cystectomy (RC) and treated with transurethral resection of bladder tumour followed by concomitant radio-chemotherapy (platinum salt and 5-fluorouracil) at two institutions (Saint Louis Hospital, Paris, France and European Georges Pompidou Hospital, Paris, France) between 1990 and 2021. RT consisted of an adapted bifractionated split-course hypofractionated RT. Acute toxicities were reported according to Common Terminology Criteria for Adverse Events version 5.0 and late toxicities were reported according to the Radiation Therapy Oncology Group/European Organisation for Research and Treatment of Cancer late radiation morbidity scoring schema. The primary end-point was overall survival (OS). Secondary end-points included other survivals outcomes and safety., Results: A total of 122 patients were identified, with a median (range) follow-up of 51.1 (0.5-210.8) months. In all, 83.5% of patients completed radio-chemotherapy. The OS rate was 61.7% at 3 years and 51.2% at 5 years. In multivariate analysis, the completion of RT and concomitant chemotherapy were significantly associated with better OS and cancer-specific survival. For patients fit for RC, a complete histological response was achieved for 77 patients (91.7%) with radio-chemotherapy and the bladder conservation rate was 90.5%. Acute and late Grade ≥3 toxicities were <5%., Conclusion: Bifractionated split-course hypofractionated RT with concomitant chemotherapy regimen appears to be well-tolerated and effective. Trimodal treatment seems to be a curative option for elderly patients unfit for radical surgery compared with palliative care and may contribute to improved survival in these patients., (© 2023 BJU International.)

Objectives: To describe the clinico-pathological characteristics of non-muscle-invasive bladder cancer (NMIBC) treated in metropolitan France over 1 year when bacille Calmette-Guérin (BCG) was subject to a national quota, and to document, in the context of recurrent shortages of intravesical BCG for NMIBC, the real-life indications for adjuvant treatment., Materials and Methods: Between February 2021 and February 2022, the French National Agency for the Safety of Medicines (ANSM) asked the French Association of Urology to propose a science-based quota solution for BCG using a clinical score. The ANSM then asked the distributor of the drug, MEDAC, to collect the scores for all patients for whom BCG was requested by healthcare institutions and to prioritize the requests for patients with the highest scores. Tumour stage, grade, size, number, time to recurrence, carcinoma in situ, age, accessibility of alternative treatments (total cystectomy, radio-chemotherapy, thermo-chemotherapy) and BCG treatment progress (initiation or maintenance) were documented for each intravesical BCG prescription. A descriptive analysis of the data collected during the quota year was performed., Results: During the 1-year quota, 25 878 requests for BCG were made for 19 024 patients, 60.5% of whom were aged ≥70 years. Requests for induction and maintenance treatment accounted for 12 704 (49.1%) and 13 174 prescriptions (50.9%), respectively. NMIBC treated with BCG maintenance therapy was more frequently high-risk NMIBC (91.7% vs 90.2%; P < 0.0001) than NMIBC for which induction therapy was requested. The number of cases of NMIBC leading to BCG adjuvant treatment was estimated at 12 704 cases/66 062 188 inhabitants over 1 year in metropolitan France., Conclusions: Our data suggest that the incidence of NMIBC at high risk of recurrence and progression is underestimated in reference epidemiological studies. These results should help to better define future care needs., (© 2022 BJU International.)

Objective: To evaluate the incidence and survival outcomes of histological variants of upper tract urothelial carcinoma (UTUC) treated with radical nephroureterectomy (RNU)., Materials and Methods: We retrospectively analysed data from 1610 patients treated with RNU for clinically non-metastatic UTUC between 1990 and 2016 in several centres participating in the UTUC Collaboration. Histological variants were classified as micropapillary, squamous, sarcomatoid and other, including other rare variants (<10 cases for each). Multivariable competing risk analyses were conducted to assess the effect of variant histology on overall recurrence and cancer-specific mortality (CSM)., Results: Overall, 1460 patients (91%) had pure urothelial carcinoma (PUC), whereas 150 (9%) were diagnosed with a variant histology, including 89 (5.0%), 41 (2.0%), 10 (1.0%) and 10 (1.0%) cases of micropapillary, squamous, sarcomatoid and other tumours, respectively. Variant histology was associated with the presence of adverse pathological features compared with PUC, including non-organ-confined disease (59% vs 38%; P < 0.001), lymph node invasion (28% vs 24%; P = 0.02), high-grade disease (88% vs 71%; P < 0.001), tumour necrosis (28% vs 16%; P = 0.001) and positive surgical margins (15% vs 8%; P = 0.01). In competing risk analysis, micropapillary variant was the only factor associated with worse recurrence (sub-hazard ratio [SHR] 2.27, 95% confidence interval [CI] 1.25-4.79; P = 0.02) whereas sarcomatoid variant was associated with worse CSM (SHR 16.8, 95% CI 6.86-41.17; P < 0.001)., Conclusion: We found that one out of 10 patients with UTUC treated with RNU had variant histology. Only micropapillary and sarcomatoid variants were associated with poorer oncological outcomes after adjusting for available confounding factors., (© 2019 The Authors BJU International © 2019 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.)

Objective: To analyse the outcomes of adjuvant chemotherapy vs observation in a multicentre cohort of patients with upper tract urothelial carcinoma (UTUC) in order to clarify whether such patients benefit from adjuvant chemotherapy after radical nephroureterectomy (RNU)., Patients and Methods: Data from 15 centres were collected for a total of 1544 patients, treated between 2000 and 2015. Criteria for patient selection included pT2-4N0/x stage, or lymph node-positive disease, and prior RNU. The standardized difference approach was used to compare subgroup characteristics. Overall survival (OS) was the primary endpoint. The primary analysis used 1:1 propensity score matching, with inverse probability of treatment weighting in addition to this in the secondary analysis. The latter was also performed with the inclusion of covariates, i.e. with 'doubly robust' estimation. A 6-month landmark analysis was performed to exclude early events., Results: A total of 312 patients received adjuvant chemotherapy and 1232 underwent observation. Despite differences between the two groups, the standardized difference was generally <10% after matching. In the matched analysis no difference was observed in OS between adjuvant chemotherapy and observation (hazard ratio [HR] 1.14, 95% confidence inverval [CI] 0.91-1.43; P = 0.268). In the doubly robust estimate-adjusted comparison, adjuvant chemotherapy was significantly associated with shorter OS (HR 1.26, 95% CI 1.02-1.54; P = 0.032). Similar findings were confirmed in subgroup analyses stratified by pathological stage, and after landmark analysis. Results should be interpreted with consideration given to the inherent limitations of retrospective studies., Conclusion: Adjuvant chemotherapy did not improve OS compared with observation in the present study. These results contribute to the uncertainties regarding postoperative chemotherapy in UTUC, and suggest dedicated prospective trials, new more potent therapies, and the identification of enhanced patient selection criteria are required., (© 2017 The Authors BJU International © 2017 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.)

Objectives: To determine if a re-transurethral resection (TUR), in the presence or absence of muscle at the first TUR in patients with T1-high grade (HG)/Grade 3 (G3) bladder cancer, makes a difference in recurrence, progression, cancer specific (CSS) and overall survival (OS)., Patients and Methods: In a large retrospective multicentre cohort of 2451 patients with T1-HG/G3 initially treated with bacille Calmette-Guérin, 935 (38%) had a re-TUR. According to the presence or absence of muscle in the specimen of the primary TUR, patients were divided in four groups: group 1 (no muscle, no re-TUR), group 2 (no muscle, re-TUR), group 3 (muscle, no re-TUR) and group 4 (muscle, re-TUR). Clinical outcomes were compared across the four groups., Results: Re-TUR had a positive impact on recurrence, progression, CSS and OS only if muscle was not present in the primary TUR specimen. Adjusting for the most important prognostic factors, re-TUR in the absence of muscle had a borderline significant effect on time to recurrence [hazard ratio (HR) 0.67, P = 0.08], progression (HR 0.46, P = 0.06), CSS (HR 0.31, P = 0.07) and OS (HR 0.48, P = 0.05). Re-TUR in the presence of muscle in the primary TUR specimen did not improve the outcome for any of the endpoints., Conclusions: Our retrospective analysis suggests that re-TUR may not be necessary in patients with T1-HG/G3, if muscle is present in the specimen of the primary TUR., (© 2015 The Authors BJU International © 2015 BJU International Published by John Wiley & Sons Ltd.)

Objective: To externally validate the pT4a-specific risk model for cancer-specific survival (CSS) proposed by May et al. (Urol Oncol 2013; 31: 1141-1147) and to develop a new pT4a-specific nomogram predicting CSS in an international multicentre cohort of patients undergoing radical cystectomy (RC) for urothelial carcinoma of the bladder (UCB) PATIENTS AND METHODS: Data from 856 patients with pT4a UCB treated with RC at 21 centres in Europe and North-America were assessed. The risk model proposed by May et al., which includes female gender, presence of positive lymphovascular invasion (LVI) and lack of adjuvant chemotherapy administration as adverse predictors for CSS, was applied to our cohort. For the purpose of external validation, model discrimination was measured using the receiver-operating characteristic-derived area under the curve. A nomogram for predicting CSS in pT4a UCB after RC was developed after internal validation based on multivariable Cox proportional hazards regression analysis evaluating the impact of clinicopathological variables on CSS. Decision-curve analyses were applied to determine the net benefit derived from the two models., Results: The estimated 5-year-CSS after RC was 34% in our cohort. The risk model devised by May et al. predicted individual 5-year-CSS with an accuracy of 60.1%. In multivariable Cox proportional hazards regression analysis, female gender (hazard ratio [HR] 1.45), LVI (HR 1.37), lymph node metastases (HR 2.54), positive soft tissue surgical margins (HR 1.39), neoadjuvant (HR 2.24) and lack of adjuvant chemotherapy (HR 1.67, all P < 0.05) were independent predictors of an adverse CSS rate and formed the features of our nomogram with a predictive accuracy of 67.1%. Decision-curve analyses showed higher net benefits for the use of the newly developed nomogram in our cohort over all thresholds., Conclusions: The risk model devised by May et al. was validated with moderate discrimination and was outperformed by our newly developed pT4a-specific nomogram in the present study population. Our nomogram might be particularly suitable for postoperative patient counselling in the heterogeneous cohort of patients with pT4a UCB., (© 2014 The Authors BJU International © 2014 BJU International Published by John Wiley & Sons Ltd.)

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 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.)

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 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.)

Objectives: To prospectively test whether a panel of biomarkers could identify patients with organ-confined disease likely to be upstaged at radical cystectomy (RC), as retrospective studies have found that cell-cycle- and proliferation-related biomarkers can help improve prognostic accuracy after RC., Patients and Methods: We prospectively performed p53, p21, p27, Ki67, and cyclin E1 immunohistochemical staining on transurethral resection of the bladder (TURB) specimens from 87 patients treated with RC for organ-confined urothelial carcinoma of the bladder (UCB). The number of altered biomarkers was categorised as 'favourable' (≤2 altered markers) or 'unfavourable' (>2)., Results: Expression of p53, p21, p27, cyclin E1, and Ki67 were altered in 61 (70%), 19 (22%), 26 (30%), four (5%), and 70 (80%) patients, respectively. The median number of positive markers was two. In all, 47 (54%) patients were upstaged when T-stage was considered alone and 49 (56%) when T- and/or N-stage were considered both as upstaging. In multivariable analyses that adjusted for the effects of age, clinical stage, concomitant carcinoma in situ, and time from TURB to RC, an 'unfavourable' biomarker score was independently associated with T-stage upstaging (hazard ratio [HR] 3.3, P = 0.024) but not T- and/or N-stage upstaging (HR 2.76, P = 0.06). Addition of p27, number of positive markers, and biomarker score each increased the discrimination of a base model for prediction of T-stage upstaging (5%, 6%, and 5%, respectively) and T- and/or N-stage upstaging (4%, 6%, and 3%, respectively)., Conclusions: Cell-cycle- and proliferation-related markers in the TURB specimen improve the prediction of upstaging at RC. Such a marker panel may help identify patients with non-muscle-invasive UCB who are clinically under-staged needing RC and patients with muscle-invasive UCB who are likely to be non-organ-confined thereby potentially benefiting from neoadjuvant chemotherapy., (© 2013 The Authors. BJU International © 2013 BJU International.)

Objective: To assess the association between diabetes mellitus (DM) and metformin use with prognosis and outcomes of non-muscle-invasive bladder cancer (NMIBC) PATIENTS AND METHODS: We retrospectively evaluated 1117 patients with NMIBC treated at four institutions between 1996 and 2007. Cox regression models were used to analyse the association of DM and metformin use with disease recurrence, disease progression, cancer-specific mortality and any-cause mortality., Results: Of the 1117 patients, 125 (11.1%) had DM and 43 (3.8%) used metformin. Within a median (interquartile range) follow-up of 64 (22-106) months, 469 (42.0%) patients experienced disease recurrence, 103 (9.2%) experienced disease progression, 50 (4.5%) died from bladder cancer and 249 (22.3%) died from other causes. In multivariable Cox regression analyses, patients with DM who did not take metformin had a greater risk of disease recurrence (hazard ratio [HR]: 1.45, 95% confidence interval [CI] 1.09-1.94, P = 0.01) and progression (HR: 2.38, 95% CI 1.40-4.06, P = 0.001) but not any-cause mortality than patients without DM. DM with metformin use was independently associated with a lower risk of disease recurrence (HR: 0.50, 95% CI 0.27-0.94, P = 0.03)., Conclusion: Patients with DM and NMIBC who do not take metformin seem to be at an increased risk of disease recurrence and progression; metformin use seems to exert a protective effect with regard to disease recurrence. The mechanisms behind the impact of DM on patients with NMIBC and the potential protective effect of metformin need further elucidation., (© 2013 The Authors. BJU International © 2013 BJU International.)

Objective: To evaluate the gender-specific differential effects of smoking habits and cumulative smoking exposure on outcomes in patients with upper tract urothelial carcinoma (UTUC) treated with radical nephroureterectomy (RNU)., Patients and Methods: A total of 864 consecutive patients, comprising 553 (64%) men and 311 (36%) women, from five international institutions underwent RNU without neoadjuvant chemotherapy. Smoking history included smoking status (current, former or never), quantity of cigarettes per day (CPD), smoking duration in years and years since smoking cessation. Cumulative smoking exposure was categorized 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). Uni- and multivariable competing risk regression models were used to assess the associations with outcomes., Results: Overall, 244 (28.2%), 297 (34.4%) and 323 (37.4%) patients were never, former and current smokers, respectively. There were no differences in smoking status, quantity and duration between the genders. In female ever smokers, 30 (9.6%), 121 (38.9%) and 67 (21.5%) were light short-term, moderate and heavy long-term smokers, respectively. Compared with men, female current smokers were more likely to experience disease recurrence in univariable analysis (P = 0.013). In heavy long-term smokers, female gender was significantly associated with disease recurrence (hazard ratio [HR] 1.7; P = 0.03) and cancer-specific mortality (HR 2.0; P = 0.009) in multivariable analysis that adjusted for standard clinico-pathological features. In female patients only, smoking quantity, duration and cumulative exposure were associated with disease recurrence and cancer-specific mortality on multivariable analyses (P ≤ 0.025)., Conclusions: The impact of smoking on UTUC outcomes after RNU is gender-specific. Females who are current and heavy long-term smokers experience worse outcomes than their male counterparts. Further research is needed to elucidate the molecular mechanisms underlying the gender-specific differential effect of smoking on UTUC outcomes., (© 2013 BJU International.)

Unlabelled: What's known on the subject? and what does the study add?: Radical nephroureterectomy (RNU), the standard of care treatment for high-risk urothelial carcinoma of the upper tract (UTUC), results in loss of a renal unit. Loss of renal function decreases eligibility for systemic chemotherapies and results in decreased overall survival in various malignancies. The study shows that only a small proportion of patients had a preoperative renal function that would allow cisplatin-based chemotherapy. Moreover, eGFR significantly decreased after RNU, thereby lowering the rate of cisplatin eligibility to only 16 and 52% of patients based on the thresholds of 60 and 45 mL/min/1.73 m(2) , respectively. Taken together with the rest of the literature, the findings of the study support the use of cisplatin-based chemotherapy, when indicated, in the neoadjuvant rather than adjuvant setting., Objective: To report (i) the estimated glomerular filtration rate (eGFR) changes in patients undergoing radical nephro-ureterectomy (RNU) for upper tract urothelial carcinoma (UTUC); (ii) the rate of change in eGFR in patients eligible for cisplatin-based chemotherapy; and (iii) the association of preoperative, postoperative and rate of change of renal function variables with survival outcomes., Patient and Methods: We performed a retrospective analysis of 666 patients treated with RNU for UTUC at seven international institutions from 1994 to 2007. The eGFR was calculated at baseline and at 3-6 months (Modification of Diet in Renal Disease formula (MDRD) and Chronic Kidney Disease Epidemiology Collaboration formula (CKD-EP) equations)., Results: The median (interquartile range) eGFR decreased by 18.2 (8-12)% after RNU. A total of 37% of patients had a preoperative eGFR ≥ 60 mL/min/1.73 m(2) , which decreased to 16% after RNU (P < 0.001); 72% of patients had a preoperative eGFR ≥ 45 mL/min/1.73 m(2) , which decreased to 52% after RNU (P < 0.001). The distributions were similar when analyses were restricted to patients with locally advanced disease (pT3-pT4) and/or lymph node metastasis. Patients older than the median age of 70 years were more likely to have a decrease in eGFR after RNU (P < 0.001). None of the renal function variables was associated with clinical outcomes such as disease recurrence, cancer-specific and overall mortality; however, when analyses were restricted to patients who had no adjuvant chemotherapy and did not experience disease recurrence (n = 431), a preoperative eGFR ≥ 60 mL/min/1.73 m(2) (P = 0.03) and a postoperative eGFR ≥ 45 mL/min/1.73 m(2) (P = 0.04) were associated with better overall survival in univariable analyses., Conclusions: In patients who had UTUC, eGFR was low and furthermore, it significantly decreased after RNU. Renal function did not affect cancer-specific outcomes after RNU., (© 2013 BJU International.)

Objectives: To assess the impact of statin use on outcomes of patients with non-muscle-invasive bladder cancer (NMIBC). To measure the effect of statin use on the efficacy of intravesical bacillus Calmette-Guérin (BCG) therapy., Patients and Methods: A retrospective analysis was performed on 1117 patients treated with transurethral resection of the bladder (TURB) for NMIBC at three institutions between 1996 and 2007. Statin use at the time of diagnosis was recorded for each patient. Univariable Cox regression models addressed the association of statin use with disease recurrence, disease progression, cancer-specific mortality and overall mortality in all patients, patients with primary NMIBC, patients not treated with BCG, and patients treated with BCG., Results: Overall, 341 patients (30.5%) used statins and 776 (69.5%) did not. Within a median (interquartile range) follow-up of 62.7 (25.0-110.7) months, 469 patients (42.0%) experienced disease recurrence, 103 (9.2%) progression, 50 (4.5%) cancer-specific mortality, and 299 (26.8%) any-cause mortality. In univariable Cox regression analyses, statin use was not associated with any of these four endpoints (P > 0.05 for all). In subgroup analyses, statin use was also not associated with prognosis in patients with primary NMIBC or patients not receiving BCG (P > 0.05 for all four endpoints). Statin use was not associated with response to BCG (P > 0.05 for all four endpoints)., Conclusion: Statin users did not experience different outcomes compared with non-users and statin use did not affect the efficacy of BCG immunotherapy; these data do not support modification or discontinuation of statin therapy for patients with NMIBC., (© 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.)

Unlabelled: Study Type - Therapy (cost effectiveness analysis) Level of Evidence 2a What's known on the subject? and What does the study add? Bladder cancer is one of the costliest malignancies to treat throughout the life of a patient. The most cost-effective management for low-risk non-muscle-invasive bladder cancer is not known. The current study shows that employing cystoscopic office fulguration for low-risk appearing bladder cancer recurrences can materially impact the cost-effectiveness of therapy. In a follow-up protocol where office fulguration is routinely employed for low-risk bladder cancers, peri-operative intravesical chemotherapy may not provide any additional cost-effectiveness benefit., Objective: To examine the cost-effectiveness of fulguration vs transurethral resection of bladder tumour (TURBT) with and without perioperative intravesical chemotherapy (PIC) for managing low-risk carcinoma not invading bladder muscle (NMIBC). Low-risk NMIBC carries a low progression rate, lending support to the use of office-based fulguration for small recurrences rather than traditional TURBT., Materials and Methods: A Markov state transition model was created to simulate treatment of NMIBC with vs without PIC, with recurrence treated by formal TURBT vs treatment with fulguration. Costing data were obtained from the Medicare Resource Based Relative Value Scale. Data regarding the success of PIC were obtained from the peer-reviewed literature, as were corresponding utilities for bladder cancer-related procedures. Sensitivity analyses were performed., Results: At 5-year follow-up, a strategy of fulguration without PIC was the most cost-effective (mean cost-effectiveness = US $654.8/quality-adjusted life year), despite a lower recurrence rate with PIC. Both fulguration strategies dominated each TURBT strategy. Sensitivity analysis showed that fulguration without PIC dominated all other strategies when the recurrence rate after PIC was increased to ≥14.2% per year. Similarly, the cost-effectiveness of TURBT becomes more competitive with fulguration when the total cost of TURBT declines < US $1175., Conclusions: The present study shows that fulguration without PIC was the most cost-effective strategy for treating low-risk NMIBC. The effectiveness of PIC and the cost of TURBT can materially impact the cost-effectiveness of the different management strategies. These results should be considered in treatment decisions in the context of preserving oncological control., (© 2012 BJU INTERNATIONAL.)

Unlabelled: Study Type - Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Outcomes after disease recurrence in patients with urothelial carcinoma of the bladder treated with radical cystectomy are variable, but the majority of patients die from the disease within 2 years after disease recurrence. Knowledge about prognostic factors that may influence survival after disease recurrence is limited. We found that outcomes after disease recurrence in patients with urothelial carcinoma of the bladder are significantly affected by common clinicopathological factors. In addition, a shorter time from surgery to disease recurrence is significantly associated with poor outcomes. These factors should be considered when scheduling salvage chemotherapy protocols/clinical trials., Objective: To describe the natural history following disease recurrence after radical cystectomy (RC) and to identify prognostic factors that influence cancer-specific survival with special focus on time from RC to disease recurrence., Methods: We identified 1545 patients from 16 international institutions who experienced disease recurrence after RC and bilateral lymphadenectomy. None of the patients received preoperative chemotherapy; 549 patients received adjuvant chemotherapy. A multivariable Cox regression model addressed time to cancer-specific mortality after disease recurrence., Results: The median cancer-specific survival time after disease recurrence was 6.9 months (95% CI 6.3-7.4). Overall, 1254 of 1545 patients died from urothelial carcinoma of the bladder and 47 patients died from other causes. The actuarial cancer-specific survival estimate at 12 months after disease recurrence was 32%. On multivariable analysis, non-organ-confined tumour stages (hazard ratio [HR] 1.38, P= 0.002), lymph node metastasis (HR 1.25, P < 0.001), positive soft tissue surgical margin (HR 1.32, P= 0.002), female gender (HR 1.21, P= 0.003), advanced age (HR 1.16, P < 0.001) and a shorter interval from surgery to disease recurrence (P < 0.001) were significantly associated with cancer-specific mortality. The adjusted risk of death from cancer within 1 year after disease recurrence for patients who recurred 6, 12 and 24 months after surgery was 70%, 64% and 60%, respectively., Conclusions: Over two-thirds of patients who experience disease recurrence of urothelial carcinoma of the bladder after RC die within 12 months. Common clinicopathological factors are strongly associated with cancer-specific mortality. A shorter time from surgery to disease recurrence is significantly associated with poor outcomes. Accurate risk stratification could help in patient counselling and decision-making regarding salvage treatment., (© 2012 BJU INTERNATIONAL.)

Objectives: To identify clinicopathological factors that predict outcomes in patients with a single lymph node (LN) metastasis (pN1) treated with radical cystectomy (RC) for urothelial carcinoma of the bladder (UCB). LN metastasis is an established predictor of clinical outcomes in patients. While most patients with large LN burden experience disease recurrence, lymphadenectomy can be curative in patients with pN1 disease., Patients and Methods: We analysed 381 patients with pN1 UCB from a multi-institutional cohort of 4335 patients with UCB treated with RC and lymphadenectomy without preoperative chemo- or radiotherapy. Subgroup analyses were performed for patients with ≥9 LNs removed and according to adjuvant chemotherapy administration (n = 215)., Results: The median (interquartile range, IQR) LN number was 15 (19) and the median (IQR) LN density was 6.7 (7.5)%. Within a median follow-up of 41 months, the mean (+/- SD) 2- and 5-year cancer-specific survival (CSS) rates were 55 (3)% and 46 (3)%, respectively. On multivariable analysis that adjusted for the effects of standard clinicopathological features, female gender (hazard ratio [HR] 1.48, P = 0.023), higher tumour stage (HR 1.68, P = 0.007), positive soft tissue surgical margin (STSM; HR 2.06, P = 0.004), higher LN density (HR 2.99, P = 0.025) and absence of adjuvant chemotherapy (HR 0.70, P = 0.026) were independently associated with CSS. In subgroup analyses of patients with ≥9 LNs removed, tumour stage and STSM status remained independent predictors for CSS (P = 0.009 and P < 0.001, respectively)., Conclusions: About half of the patients with pN1 UCB died from UCB within 5 years of RC. Pathological stage and STSM status are strong predictors for outcomes. Accurate prediction of the individual risk of CSS may help risk stratifying pN1 UCB in order to help improve clinical-decision making. Patients with pN1 UCB presenting with additional unfavourable risk factors need a closer follow-up scheduling and might receive adjuvant therapy., (© 2012 The Authors BJU International © 2012 BJU International.)

Unlabelled: Study Type - Diagnostic (exploratory cohort) Level of Evidence 2b What's known on the subject? and What does the study add? PCA3 scores correlate to numerous histoprognostic factors, specifically tumour volume and positive surgical margins. These results may have a clinical impact in the near future on the selection of patients eligible to undergo active surveillance and nerve-sparing surgery., Objective: To assess correlations between Prostate CAncer gene 3 (PCA3) levels and pathological features of radical prostatectomy (RP) specimens, which define cancer aggressiveness., Patients and Methods: After digital rectal examination (DRE), first-catch urine was collected from 160 patients with localized prostate cancer. The PCA3 score was calculated using the Gene Probe Progensa(™) assay. PCA3 scores were then correlated to the pathological features of the RP specimens., Results: PCA3 scores correlated significantly with tumour volume (r= 0.34, P < 0.01). A PCA3 score of >35 was an independent predictor in a multivariate analysis of a tumour volume >0.5 mL (odds ratio [OR] 2.7, P= 0.04). It was also an independent predictor of positive surgical margins (OR 2.4, P= 0.04). Receiver-operator characteristic curves indicated PCA3 as the most accurate predictor of positive margins (area under the curve [AUC] 0.62), in addition to a positive biopsy percentage (AUC 0.52). There was also a significant difference in the mean PCA3 score between Gleason score patient groups (6 vs ≥ 7) and pathological stage groups (pT0/2 vs pT3/4)., Conclusions: PCA3 scores correlate to numerous histoprognostic factors, specifically tumour volume and positive surgical margins. These results may have a clinical impact in the near future on the selection of patients eligible to undergo active surveillance and nerve-sparing surgery., (© 2012 BJU INTERNATIONAL.)

Objective: • To assess the mid-term (3 years of follow-up) oncological control of laparoscopic radical cystectomy (LRC) for high-grade muscle-invasive bladder cancer in a well studied male population., Patients and Methods: • We assessed 40 men with bladder cancer (mean [range] age 66.5 [50-75] years) who underwent LRC and extended pelvic lymphadenectomy at our institution between April 2004 and September 2008. • Of the 40 patients, 13 (32.5%) had a complete laparoscopic procedure (ileal conduit: seven patients; neobladder: five patients; bilateral ureterostomy: one patient) and 27 (67.5%) had an LRC procedure only (ileal conduit: 15 patients; neobladder: 12 patients)., Results: • No major complications were observed intraoperatively. • The mean operating time was 407 min and the mean blood loss was 720 mL. Four patients (10%) required conversion to open surgery. The mean (range) hospital stay was 10.2 (7-25) days. One patient died of myocardial infarction in the postoperative period. • Pathological analysis showed organ-confined tumours (stage pT0/pT1/pT2/pT3a) in 22 patients (55%) and extravesical disease (pT3/pT4) in 18 (45%). Of the 40 patients, six (15%) had lymph node involvement. The mean (range) number of nodes removed was 19.9 (5-40). • At a mean (range) follow-up period of 36 (0-72) months, 26 patients were alive with no evidence of disease (disease-free survival rate 67%)., Conclusion: • Laparoscopic radical cystectomy is a safe, feasible, and effective alternative to open radical cystectomy (ORC). The 3-year oncological efficacy was comparable with that of ORC., (© 2011 THE AUTHORS. BJU INTERNATIONAL © 2011 BJU INTERNATIONAL.)

Unlabelled: Study Type - Diagnostic (case series)., Level of Evidence: 4., Objective: • To investigate the role of magnetic resonance imaging (MRI) in selecting patients for active surveillance (AS)., Patients and Methods: • We identified prostate cancers patients who had undergone a 21-core biopsy scheme and fulfilled the criteria as follows: prostate-specific antigen (PSA) level ≤ 10 ng/mL, T1-T2a disease, a Gleason score ≤ 6, <3 positive cores and tumour length per core <3 mm. • We included 96 patients who underwent a radical prostatectomy (RP) and a prostate MRI before surgery. • The main end point of the study was the unfavourable disease features at RP, with or without the use of MRI as AS inclusion criterion., Results: • Mean age and mean PSA were 62.4 years and 6.1 ng/mL, respectively. Prostate cancer was staged pT3 in 17.7% of cases. • The rate of unfavourable disease (pT3-4 and/or Gleason score ≥ 4 + 3) was 24.0%. A T3 disease on MRI was noted in 28 men (29.2%). MRI was not a significant predictor of pT3 disease in RP specimens (P = 0.980), rate of unfavourable disease (P = 0.604), positive surgical margins (P = 0.750) or Gleason upgrading (P = 0.314). • In a logistic regression model, no preoperative parameter was an independent predictor of unfavourable disease in the RP specimen. • After a mean follow-up of 29 months, the recurrence-free survival (RFS) was statistically equivalent between men with T3 on MRI and those with T1-T2 disease (P = 0.853)., Conclusion: • The results of the present study emphasize that, when the selection of patients for AS is based on an extended 21-core biopsy scheme, and uses the most stringent inclusion criteria, MRI does not improve the prediction of high-risk and/or non organ-confined disease in a RP specimen., (© 2010 THE AUTHORS. BJU INTERNATIONAL © 2010 BJU INTERNATIONAL.)

Objective: • To investigate the relationship between pretreatment testosterone levels and pathological specimen characteristics, by prospectively examining serum androgen concentrations in a well-studied cohort of patients who underwent radical prostatectomy (RP) for localized prostate cancer., Patients and Methods: • A total of 107 patients with clinically localized prostate cancer had an assay of total testosterone before laparoscopic RP at our institution. • The results were classified into two groups based on the total serum testosterone: group1, < 3 ng/mL; group 2, ≥ 3 ng/mL. • Student's t-test was used to compare continuous variables, and Fisher's exact test or the chi-squared test was used to compare categorical variables. • Survival curves were established using the Kaplan-Meier method and compared using the log-rank test. In all tests, P < 0.05 was considered to indicate statistical significance., Results: • All patients had localized prostate cancer based on digital rectal examination (DRE) and preoperative magnetic resonance imaging (MRI). Groups 1 and 2 were similar in terms of age, body mass index, preoperative co-morbidities (cardiovascular and diabetes mellitus), clinical stage of prostate cancer and preoperative PSA levels. • In pathological specimens, low total testosterone (< 3 ng/mL) was an independent risk factor for high Gleason score (> 7) and for locally advanced pathological stage (pT3 and pT4). • Higher preoperative testosterone correlated with disease confined to the gland. • There was no association between serum testosterone levels and surgical margin status, on the one hand, and biochemical recurrence on the other., Conclusion: • Low serum testosterone appears to be predictive of aggressive disease (Gleason score >7 and extraprostatic disease, pathological stage > pT2) in patients who underwent RP for localized prostate cancer., (© 2010 THE AUTHORS. BJU INTERNATIONAL © 2010 BJU INTERNATIONAL.)

Objective: To determine the proportion of patients who are continent, potent and cancer-free (trifecta rate) 2 years after extraperitoneal laparoscopic radical prostatectomy (ELRP)., Patients and Methods: We included patients who underwent an ELRP at our department and who were followed for at least 2 years. Those who were impotent or incontinent before the surgery were excluded from the analysis. Overall, 911 men were included. All patients prospectively completed objective, self-administered questionnaires before the medical visit, concerning their voiding and sexual disorders, before surgery and 12 and 24 months after ELRP. Biochemical recurrence was defined as any detectable serum PSA (≥ 0.2 ng/mL). Potency was defined as the ability to achieve an erection sufficient for penetration with or without the use of phosphodiesterase-5 enzyme inhibitor. Urinary continence was defined as absence, or occasional use, of a pad for anticipated vigorous activity. The primary study endpoint was the trifecta rate (cancer control, continence and potency) at 2 years after the surgery. Factors associated with the trifecta outcome were assessed in univariate analysis., Results: Median age and PSA level were 62.2 years and 9.9 ng/mL, respectively. A trifecta outcome was achieved in 29.7 and 54.4% of patients at 12 and 24 months, respectively. The 2-year trifecta rate reached 63.5% in patients undergoing bilateral nerve-sparing surgery and 73.5% in men aged < 60 years. Age < 60 years, PSA level < 10 ng/mL, organ-confined disease and bilateral nerve-sparing procedure were significantly associated with the 2-year trifecta outcome. A total of 84.8% of patients were both cancer-free and continent at 24 months, regardless of erectile function., Conclusions: Two years after ELRP, the trifecta outcome is achieved in 54.4% of patients who remained potent and continent. This rate reaches 63.5% in patients undergoing a bilateral nerve-sparing procedure. Combined results of good cancer control and continence recovery are reported in 84.8% of patients, regardless of erectile function., (© 2010 THE AUTHORS. JOURNAL COMPILATION © 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.)

Objective: To study the development of stage migration in prostate cancer after controlling for the number of biopsy cores., Patients and Methods: In all, 1826 patients had a first set of 21-core biopsies taken between 2001 and 2008. Among the 801 patients with prostate cancer, 443 had a laparoscopic radical prostatectomy (RP). Patients were divided into three subsets according to the date of biopsy, i.e. period 1 (2001-2003), period 2 (2004-2005), and period 3 (2006-2008). Study end points were the development over time of: (i) clinico-biological characteristics; (ii) biopsy variables; (iii) pathological RP features; and (iv) the biochemical recurrence-free (RFS) rate after surgery., Results: The mean age decreased significantly over time (P = 0.004). The proportion of men with a prostate-specific antigen (PSA) level of 4-10 ng/mL increased significantly over time at the expense of the proportion of men with a PSA level of ≥ 10 ng/mL (P = 0.004). A biopsy Gleason score of ≥ 7 was reported in 53.9% of period 1, compared to 39.6% in period 3 (P = 0.001). RP specimens had a significantly lower proportion of extraprostatic disease (P = 0.013), of high Gleason scores (P = 0.049), and positive margins (P = 0.011) over time. The RFS curves did not vary over time (P = 897)., Conclusion: Current candidates for prostate biopsy are younger and have lower PSA levels than those who had biopsies taken at the beginning of the decade. Cancers are less aggressive in terms of Gleason score, extent of the disease on biopsy cores and rate of extraprostatic disease on RP specimens than those diagnosed at the beginning of the decade., (© 2010 THE AUTHORS. JOURNAL COMPILATION © 2010 BJU INTERNATIONAL.)

Objective: To describe our current procedure of robot-assisted laparoscopic radical prostatectomy (RALP), and to assess the effect of the learning curve on perioperative data, early oncological outcomes and functional results, as RALP has increasingly become a treatment option for men with localized prostate cancer., Patients and Methods: In all, 206 consecutive men had a RALP between July 2001 and November 2008 for localized prostate cancer. Among the overall cohort, the 175 men operated on by the same surgeon were distributed into five groups according to the chronological order of the procedures. The mean follow-up after RALP was 18.3 months. Patient demographics, surgical data and postoperative variables were collected into a prospective database. Data were compared by chronological groups into single-surgeon cohort., Results: The median operative time and blood loss were 140 min and 350 mL, respectively. The complication rate was 8.3%. Cancers were pT3-4 in 34.5%. The mean hospital stay and duration of bladder catheterization were 4.3 and 8.2 days, respectively. The rate of positive surgical margins (PSMs) was 17.2% in pT2 cancers. The recovery rate of continence was 98% at 12 months. Intraoperative time, blood loss and length of hospital stay were significantly improved after a short learning curve. The continence recovery, the rate and the length of PSM were also improved beyond the learning curve, but difference was not statistically significant., Conclusions: RALP is a safe and reproducible procedure and offers a short learning curve for experienced laparoscopic surgeons. Beyond the learning curve, continued experience might also provide further improvements in terms of operative, pathological and functional results., (© 2009 THE AUTHORS. JOURNAL COMPILATION © 2009 BJU INTERNATIONAL.)

Objective: To establish the predictive accuracy of the Kattan preoperative nomogram by comparing predictions at 5 years with actual progression in patients who had a radical prostatectomy (RP)., Materials and Methods: We reviewed the data for 928 patients treated by RP as a first-line treatment for localized prostate cancer, between 1994 and 2005. Recurrence was defined as one prostate-specific antigen (PSA) level of >0.4 ng/mL. The 5-year progression-free probability (PFP) rate was evaluated on censured data using the Kaplan-Meier method. Relationships between all predictor variables included in the Kattan nomogram (PSA level, biopsy Gleason scores and clinical stage) and survival were evaluated by Cox proportional-hazards regression analysis. The discriminating ability of the nomogram was assessed by the concordance index (c-index). Bootstrapping was used to assess confidence intervals (CIs), and then the calibration was assessed., Results: The median follow-up was 60 months. Overall, 177 (19%) patients had a recurrence; the 5-year PFP rate (95% CI) was 80.9 (78-83)%. Of the three variables included in the nomogram, all were associated with recurrence in a multivariate analysis (P < 0.001). The c-index (95% CI) was only 0.664 (0.584-0.744). In general, the nomogram was not well calibrated., Conclusions: There was a discrepancy between the predicted PFP as estimated by the Kattan nomogram and actual relapse in this group of patients. Clinicians should be aware that the nomogram is less accurate when used outside the population used to formulate the nomogram. Although more accurate tools are needed, the Kattan nomogram is still the best choice for urologists so far.

Objective: To determine the effectiveness of cancer control afforded by radical prostatectomy (RP) in patients with clinical stage T3 prostate cancer., Patients and Methods: We retrospectively reviewed data for patients treated by RP for clinical stage T3 prostate cancer between 1995 and 2005. The following case characteristics were analysed: patient age, clinical presentation, preoperative prostate-specific antigen (PSA) level, Gleason score, tumour stage (2002 Tumour-Node-Metastasis), surgical procedure, pathological data, margin and lymph node status, and recurrence. Biochemical recurrence was defined as an increase in PSA level of >0.2 ng/mL after surgery. Kaplan-Meier survival curves were generated, and prognostic factors were evaluated., Results: Overall, 100 patients were included; only 79% of them had pT3 disease based on the pathological specimen. The median follow-up after RP was 69 months. The RP was open in 77 and laparoscopic in 23, with no significant difference between these approaches (P = 0.38). The 5-year PSA-free survival after surgery was 45%, and 5-year cancer-specific survival was 90%. On univariable analysis, Gleason score >7 (P = 0.01), pathological stage (pT2-T3a vs T3b) (P < 0.001), positive lymph node (P < 0.001), and positive margin (P < 0.001) were associated with recurrence. On multivariable analysis, lymph node, margin status and Gleason score were also significant (P < 0.05)., Conclusions: RP can be recommended as an alternative primary treatment that results in acceptable cancer control for clinical stage T3 prostate cancer in selected cases. However, the patient should be warned that surgery alone might not be sufficient to control the cancer, and that adjuvant therapy might be needed during the course of the disease.