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Objective: To determine the prevalence of intra-patient inter-metastatic heterogeneity based on positron emission tomography (PET)/computed tomography (CT) in patients with metastatic castration-resistant prostate cancer (mCRPC) and to determine the prevalence of neuroendocrine disease in these patients and their eligibility for radioligand therapies (RLTs)., Patients and Methods: This multicentre observational prospective clinical study will include 100 patients with mCRPC from five Canadian academic centres. Patients with radiological or biochemical progression and harbouring at least three metastases by conventional imaging will be accrued. Intra-patient inter-metastatic heterogeneity will be determined with triple-tracer imaging using fluorine-18 fluorodeoxyglucose ( 18 F-FDG), gallium-68-( 68 Ga)-prostate-specific membrane antigen (PSMA)-617 and 68 Ga-DOTATATE, which are a glucose analogue, a PSMA receptor ligand and a somatostatin receptor ligand, respectively. The 68 Ga-PSMA-617 and 18 F-FDG PET/CT scans will be performed first. If at least one PSMA-negative/FDG-positive lesion is observed, an additional PET/CT scan with 68 Ga-DOTATATE will be performed. The tracer uptake of individual lesions will be assessed for each PET tracer and patients with lesions presenting discordant uptake profiles will be considered as having inter-metastatic heterogeneous disease and may be offered a biopsy., Expected Results: The proposed triple-tracer approach will allow whole-body mCRPC characterisation, investigating the inter-metastatic heterogeneity in order to better understand the phenotypic plasticity of prostate cancer, including the neuroendocrine transdifferentiation that occurs during mCRPC progression. Based on 68 Ga-PSMA-617 or 68 Ga-DOTATATE PET positivity, the potential eligibility of patients for PSMA and DOTATATE-based RLT will be assessed. Non-invasive whole-body determination of mCRPC heterogeneity and transdifferentiation is highly innovative and might establish the basis for new therapeutic strategies. Comparison of molecular imaging findings with biopsies will also link metastasis biology to radiomic features., Conclusion: This study will add novel, biologically relevant dimensions to molecular imaging: the non-invasive detection of inter-metastatic heterogeneity and transdifferentiation to neuroendocrine prostate cancer by using a multi-tracer PET/CT strategy to further personalise the care of patients with mCRPC., (© 2021 The Authors. BJU International published by John Wiley & Sons Ltd on behalf of BJU International.)

Objectives: To assess the efficacy of neoadjuvant chemotherapy (NAC) before radical cystectomy (RC) in a retrospective multicentre cohort of patients with cT2N0M0 bladder cancer (BCa) without preoperative hydronephrosis., Patients and Methods: This was a propensity-based analysis of 619 patients. Of these, 316 were treated with NAC followed by RC and 303 with upfront RC. After multiple imputations, inverse probability of treatment weighting (IPTW) was used to account for potential selection bias. Multivariable logistic regression analysis was performed to evaluate the impact of NAC on pathological complete response and downstaging at RC, while IPTW-adjusted Kaplan-Meier curves and Cox regression models were built to evaluate the impact of NAC on overall survival (OS)., Results: After IPTW-adjusted analysis, standardised differences between groups were <15%. A complete response (pT0N0) at final pathology was achieved in 94 (30%) patients receiving NAC and nine (3%) undergoing upfront RC. Downstaging to non-muscle-invasive disease (

Objective: To assess the differential response to neoadjuvant chemotherapy (NAC) in patients with urothelial carcinoma of the bladder (UCB) compared to upper tract urothelial carcioma (UTUC) treated with radical surgery., Patients and Methods: Data from 1299 patients with UCB and 276 with UTUC were obtained from multicentric collaborations. The association of disease location (UCB vs UTUC) with pathological complete response (pCR, defined as a post-treatment pathological stage ypT0N0) and pathological objective response (pOR, defined as ypT0-Ta-Tis-T1N0) after NAC was evaluated using logistic regression analyses. The association with overall (OS) and cancer-specific survival (CSS) was evaluated using Cox regression analyses., Results: A pCR was found in 250 (19.2%) patients with UCB and in 23 (8.3%) with UTUC (P < 0.01). A pOR was found in 523 (40.3%) patients with UCB and in 133 (48.2%) with UTUC (P = 0.02). On multivariable logistic regression analysis, patients with UTUC were less likely to have a pCR (odds ratio [OR] 0.45, 95% confidence interval [CI] 0.27-0.70; P < 0.01) and more likely to have a pOR (OR 1.57, 95% CI 1.89-2.08; P < 0.01). On univariable Cox regression analyses, UTUC was associated with better OS (hazard ratio [HR] 0.80, 95% CI 0.64-0.99, P = 0.04) and CSS (HR 0.63, 95% CI 0.49-0.83; P < 0.01). On multivariable Cox regression analyses, UTUC remained associated with CSS (HR 0.61, 95% CI 0.45-0.82; P < 0.01), but not with OS., Conclusions: Our present findings suggest that the benefit of NAC in UTUC is similar to that found in UCB. These data can be used as a benchmark to contextualise survival outcomes and plan future trial design with NAC in urothelial cancer., (© 2020 The Authors BJU International Published by John Wiley & Sons Ltd on behalf of BJU International.)

Objective: To evaluate the outcome of patients after surgical resection of isolated retroperitoneal lymph node (RPLN) recurrence of renal cell carcinoma (RCC) using a multicentre international cohort., Patients and Methods: In all, 50 patients were identified who underwent resection of isolated RPLN recurrence of RCC at four institutions after nephrectomy for pTany Nany M0 disease. Progression-free (PFS) and cancer-specific survival (CSS) were estimated using the Kaplan-Meier method. Cox proportional hazards regression models were used to assess the association of clinicopathological characteristics with disease progression., Results: The median (interquartile range, IQR) age at resection was 57.0 (50.0-62.5) years. The median (IQR) time to RPLN recurrence after nephrectomy was 12.6 (6.9-39.5) months, with no significant difference in median time to RPLN recurrence between patients with N+ disease at nephrectomy (10.7 [6.5-24.6] months) and those with Nx/pN0 disease at nephrectomy (13.7 [8.7-44.2] months) (P = 0.66). The median (IQR) size of the RPLN recurrence before resection was 2.6 (1.9-5) cm. The most common site for RPLN recurrence was within the interaortocaval region (34%). The median (IQR) follow-up after RPLN resection for patients alive at last follow-up was 28.0 (13.7-51.2) months. During follow-up, 26 patients developed RCC recurrence, at a median (IQR) of 9.9 (4.0-18.5) months after RPLN resection. Of those who developed a secondary recurrence, disease was again isolated to the retroperitoneum in seven patients. In all, 11 patients subsequently died, including 10 who died from disease. The median PFS after RPLN resection was 19.5 months, with a 3- and 5-year PFS of 40.5% and 35.4%, respectively. We also found that RPLN recurrence at ≤12 months after nephrectomy was associated with a significantly inferior median PFS (12.3 months) compared with RPLN recurrence at >12 months after nephrectomy (47.6 months; P = 0.003). Moreover, on multivariate analysis, a shorter time to recurrence remained associated with a significantly increased risk for subsequent disease progression (hazard ratio 3.51; P = 0.005)., Conclusion: Surgical resection of isolated RPLN recurrence from RCC may result in durable cancer control in appropriately selected patients. Recurrence at ≤12 months after nephrectomy was associated with a significantly increased risk of progression after resection, underscoring the importance of this variable for risk stratification. Thus, we recommend that, in the setting of isolated RPLN recurrence of RCC (in patients without precluding comorbidities), careful consideration with the patients and medical oncology colleagues be undertaken about the relative and individualised benefits of surgical resection, systemic therapy, and surveillance., (© 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 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.)

Objectives: To characterise and measure different components of preoperative delays experienced by patients with bladder cancer before radical cystectomy (RC) in the province of Quebec, Canada and to identify the predictors of long waiting times., Methods: We conducted a retrospective cohort study using the data of patients who underwent RC for bladder cancer between 2000 and 2009 in Quebec. The cohort was obtained with the linkage of two provincial health databases: the Régie de l'assurance maladie du Québec database (data on medical services dispensed to Quebec residents), and the Fichier des évenements démographiques de l'Institut de la statistique du Québec database (demographic data on births and deaths). For the entire cohort, we determined several components of delay from first medical visit related to bladder cancer symptoms until RC. Predictors of long delays were analysed using logistic regression., Results: We analysed a total of 2778 patients who met the inclusion criteria. The median urologist referral delay was 32 days. The median delays between first urologist visit and RC and between transurethral resection of bladder tumour (TURBT) to RC were 90 days and 46 days, respectively. The median overall delay was 116 days. All components of delay progressively increased from the decade of the 1990s to the decade of the 2000s. Male gender was a protective factor for several components of delay, which suggests that gender-related variations may exist in the course of care for bladder cancer (odds ratio 0.67, 95% CI 0.50-0.89 for overall delay). Patient age and gender were associated with delayed urologist referral, delayed time to TURBT, and long overall waiting time. Factors related to the health system were associated with long cystoscopy delays., Conclusion: Median preoperative delays among patients with bladder cancer have been increasing and remain unacceptably long. Patient's age, gender and type of hospital facility were associated with long waiting times., (© 2014 The Authors. BJU International © 2014 BJU International.)

Objective: To evaluate the clinical and pathological factors influencing the risk of disease progression in a cohort of patients with low-intermediate risk prostate cancer under active surveillance (AS)., Patients and Methods: We studied 300 patients diagnosed between 1992 and 2012 with prostate adenocarcinoma with favourable parameters or who refused treatment and were managed with AS. Of those, 155 patients with at least one repeat biopsy and no progression criteria at the time of the diagnosis were included for statistical analyses. Patients were followed every 3-6 months for prostate-specific antigen (PSA) measurement and physical examination. Patients were offered repeat prostatic biopsy every year. Disease progression was defined as the presence of one or more of the following criteria: ≥ 3 positive cores, >50% of cancer in at least one core, and a predominant Gleason pattern of 4., Results: For the 155 patients, the mean (sd) age at diagnosis was 67(7) years; the median (interquartile range) follow-up was 5.4(3.6-9.5) years. Of these, 67, 25, six, and two patients had two, three, four, and five repeat biopsies, respectively. At baseline, 11 (7%) patients had a Gleason score of 3+4, while the remaining 144 (93%) patients had a Gleason score of ≤ 6. In all, 50 (32.3%) patients had disease progression on repeat biopsies, with a median progression-free survival time of 7 years. The rate of disease progression decreased after the second repeat biopsy. The 5-year overall survival rate was 100%. Having a PSA density (PSAD) of >0.15 ng/mL/mL, >1 positive core, and Gleason score >6 at the time of the diagnosis was associated with a significantly higher rate of disease progression on univariate analysis (P < 0.05), while a maximum percentage of cancer in any core of >10% showed a trend toward significance for a higher progression rate (P = 0.054). On multivariate analysis, only the presence of a PSAD of >0.15 ng/mL/mL remained significant for a higher progression rate (P < 0.05). Of the 155 patients, five (3.2%) subsequently received radiotherapy, 13 (8.4%) received hormonal therapy, and 13 (8.4%) underwent radical prostatectomy., Conclusion: AS is a suitable management option for patients with clinically low-risk prostate cancer. A PSAD of >0.15 ng/mL/mL is an important predictor for disease progression., (© 2014 The Authors. BJU International © 2014 BJU International.)

Objective: To assess the incidence and clinical significance of 'skip lesions' that are present in proximal but not in distal ureteric sections, which are occasionally found during the pathological examination of ureteric margins during radical cystectomy (RC)., Patients and Methods: We identified 660 patients who underwent a RC and had at least two permanent margins for a given ureter. In all, 1173 ureters were analysed and classified as follows: 'normal' (no tumour, reactive atypia, mild or moderate dysplasia) or 'abnormal' (severe dysplasia, carcinoma in situ (CIS), or tumour). Transitions from 'normal' distal pathology to 'abnormal' on proximal section(s) determined frequency of skip lesions. Fisher's exact test and the log-rank test were used to study correlations., Results: Ureteric skip lesions were found in 4.8% patients (2.9% ureters). Pathology of skip lesions was CIS in 55.9%, transitional cell carcinoma in 23.5% and severe dysplasia in 20.6%. Skip lesions were associated with lymphovascular invasion (34.4% vs 13.7%, P = 0.004) and advanced pT stage (P = 0.007). On multivariate analysis, skip lesions correlated with lower median overall survival (OS) (inestimable vs 8.2 years, P = 0.014) in patients with pT0 or pTa disease and a trend towards lower OS (2.7 vs 8.8 years, P = 0.066) in pTis disease. Concordance between frozen distal margin and permanent proximal margin varied; sensitivity was 80% in those without and 20% in those with skip lesions., Conclusions: The presence of a ureteric skip lesion may be associated with lower survival in patients with pT0, pTa or pTis urothelial carcinoma. Thus, while uncommon, ureteric skip lesions should be reported in pathological findings., (Published 2013. This article has been contributed to by US Government employees and their work is in the public domain in the USA.)

Unlabelled: WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?Open radical nephroureterectomy (ORNU) with excision of the ipsilateral bladder cuff is a standard treatment for upper tract urothelial carcinoma (UTUC). However, over the past decade laparoscopic RNU (LRNU) has emerged as a minimally invasive surgical alternative. Data comparing the oncological efficacy of ORNU and LRNU have reported mixed results and the equivalence of these surgical techniques have not yet been established. We found that surgical approach was not independently associated with overall or disease-specific survival; however, there was a trend toward an independent association between LRNU and poorer recurrence-free survival (RFS). To our knowledge, this is the first large, multi-institutional analysis to show a trend toward inferior RFS in patients with UTUC treated with LRNU., Objective: To examine the association between surgical approach for radical nephroureterectomy (RNU) and clinical outcomes in a large, multi-institutional cohort, as there are limited data comparing the oncological efficacy of open RNU (ORNU) and laparoscopic RNU (LRNU) for upper urinary tract urothelial carcinoma (UTUC)., Patients and Methods: Institutional RNU databases containing detailed information on patients with UTUC treated between 1994 and 2009 were obtained from 10 academic centres in Canada. Data were collected on 1029 patients and combined into a relational database formatted with patient characteristics, pathological characteristics, and survival status. Surgical approach was classified as ORNU (n = 403) or LRNU (n = 446). The clinical outcomes were overall survival (OS), disease-specific survival (DSS), and recurrence-free survival (RFS). The Kaplan-Meier method and Cox proportional regression analysis were used to analyse survival data., Results: Data were evaluable for 849 of 1029 (82.5%) patients. The median (interquartile range) follow-up duration was 2.2 (0.6-5.0) years. The predicted 5-year OS (67% vs 68%, log-rank P = 0.19) and DSS (73% vs 76%, log-rank P = 0.32) rates did not differ between the ORNU and LRNU groups; however, there was a trend toward an improved predicted 5-year RFS rate in the ORNU group (43% vs 33%, log-rank P = 0.06). Multivariable Cox proportional regression analysis showed that surgical approach was not significantly associated with OS (hazard ratio [HR] 0.89, 95% confidence interval [CI] 0.63-1.27, P = 0.52) or DSS (HR 0.90, 95% CI 0.60-1.37, P = 0.64); however, there was a trend toward an independent association between surgical approach and RFS (HR 1.24, 95% CI 0.98-1.57, P = 0.08)., Conclusion: Surgical approach was not independently associated with OS or DSS but there was a trend toward an independent association between LRNU and poorer RFS. Further prospective evaluation is needed., (© 2012 BJU International.)

Unlabelled: WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: Results from well designed randomized controlled trials usually provide the strongest evidence possible in favour of one medical intervention over another. For this reason, it is of paramount importance to conduct such trials in bladder cancer, where randomized trials are lacking, in particular to answer questions that have so far confounded us or to investigate the efficacy of new diagnostic tools or interventions. This study provides a demographic analysis of randomized controlled trials published in bladder cancer between the years of 1995 and 2010, with only 238 articles identified. Less than one-third of these reported a statistical power calculation, and only 8% were double-blinded. With many publications inaccurately labelled as randomized trials, we reveal the scarcity of trials performed over the given time period, even compared with other cancers with similar incidence, and highlight the need for more well designed trials to be conducted., Objective: To demographically examine randomized controlled trials (RCTs) that have been conducted in bladder cancer over a predefined time period., Methods: Various techniques have been described to detect RCTs using different databases. We searched the MEDLINE database by crossing the heading 'Urinary bladder neoplasms' with the MeSHs 'Clinical trial$.mp. OR clinical trial.pt. OR random:.mp. OR tu.xs.' between 1995 and 2010. For the RCTs identified, analysis was performed on each RCT, placing particular emphasis on modality of intervention, cohort size, principal author, region, journal type, disease status, histology, blinding, number of centres involved, performance of a statistical power calculation, accrual status and trial support., Results: Of 5002 RCT bladder cancer papers retrieved over the given period, only 238 represented actual RCTs after manual appraisal. More than half of the RCTs investigated medical and surgical therapies (54.2%), and only half had a sample size of >100 patients. A small percentage of studies were double-blinded (8.0%), and there was an almost equal distribution of multicentre vs single centre trials (54.6% vs 45.4%). More studies were conducted in Europe (61.3%) than the rest of the world combined, with urologists principally the lead investigators in the majority (72.3%). Most studies were conducted on patients with urothelial carcinoma (97.1%), with less than one-third reporting a statistical power calculation (31.5%)., Conclusions: Only 238 RCTs were published for bladder cancer between 1995 and 2010. RCTs are under-utilized in bladder cancer. More trials need to be designed with larger sample sizes in order to optimize diagnostic and treatment strategies for patients with bladder cancer., (© 2012 BJU International.)

Objective: To investigate the association between body mass index (BMI) and oncological outcomes in patients after radical cystectomy (RC) for urothelial carcinoma of the bladder (UCB) in a large multi-institutional series., Patients and Methods: Data were collected from 4118 patients treated with RC and pelvic lymphadenectomy for UCB. Patients receiving preoperative chemotherapy or radiotherapy were excluded. Univariable and multivariable models tested the effect of BMI on disease recurrence, cancer-specific mortality and overall mortality. BMI was analysed as a continuous and categorical variable (<25 vs 25-29 vs ≥30 kg/m(2))., Results: Median BMI was 28.8 kg/m(2) (interquartile range 7.9); 25.3% had a BMI <25 kg/m(2), 32.5% had a BMI between 25 and 29.9 kg/m(2), and 42.2% had a BMI ≥30 kg/m(2). Patients with a higher BMI were older (P < 0.001), had higher tumour grade (P < 0.001), and were more likely to have positive soft tissue surgical margins (P = 0.006) compared with patients with lower BMI. In multivariable analyses that adjusted for the effects of standard clinicopathological features, BMI >30 was associated with higher risk of disease recurrence (hazard ratio (HR) 1.67, 95% confidence interval (CI) 1.46-1.91, P < 0.001), cancer-specific mortality (HR 1.43, 95% CI 1.24-1.66, P < 0.001), and overall mortality (HR 1.81, CI 1.60-2.05, P < 0.001). Themain limitation is the retrospective design of the study., Conclusions: Obesity is associated with worse cancer-specific outcomes in patients treated with RC for UCB. Focusing on patient-modifiable factors such as BMI may have significant individual and public health implications in patients with invasive UCB., (© 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: What's known on the subject? and What does the study add? Patients with positive lymph nodes at radical cystectomy have a poor prognosis. The actual outcome of patients varies based on many factors, among which lymph node density has emerged as being more informative than nodal status of TNM staging. We combined clinical data from two major cancer centres in the USA and identified patients with an adequate lymphadenectomy and no perioperative chemotherapy to understand the natural history of the disease. Using this information, we created prognostic tools incorporating lymph node density that can be used for risk stratification, patient counselling and clinical trial design., Objective: • To develop a clinical tool based on lymph node density (LND) for patient counselling after radical cystectomy and for design of clinical trials of adjuvant therapies after radical cystectomy., Patients and Methods: • Using pooled data from two comprehensive cancer centres, we identified patients with lymph node metastases after radical cystectomy who received an adequate lymph node dissection according to existing literature (resection of eight or more nodes). • Only patients who had not received neoadjuvant or adjuvant chemotherapy were included to ensure that prediction models were based on the natural course of the disease. • Thresholds for LND ranging from 5% to 35%, in 5% increments, were used to dichotomize the study population. Within each set of two groups, the Kaplan-Meier product-limit estimator was used to estimate disease-specific survival (DSS) for each group, and Cox proportional hazards regression was used to test the significance of differences in DSS between the group with higher LND and the group with lower LND. • Tables and graphs showing the relationship between LND categories and 2-year and 5-year estimated DSS were created to aid in clinical decision-making., Results: • LND was valuable as a tool for stratifying node-positive patients into different risk groups based on expected survival. • At each LND threshold from 10% to 35%, patients with higher LND had significantly worse DSS than patients with lower LND (P ≤ 0.001). • As expected, DSS in the higher-LND group worsened with each 5% increase in LND threshold: patients with LND > 35% had a 5-year DSS rate of 4%. • Using our data as a tool, multiple cut-offs can be employed to categorize patients into various risk groups with different risk. For example, patients with LND ≤ 10% have an estimated 5-year DSS rate of 61.9%, whereas patients with LND > 15% have an estimated 5-year DSS rate of 19.2%., Conclusions: • Patients with node-positive bladder cancer have poor outcomes, and survival varies widely according to LND. • Categorical LND should be used to risk-stratify patients for counselling regarding prognosis. • Furthermore, categorical LND should be used as a tool for designing and reporting on clinical trials of adjuvant therapies., (© 2012 BJU INTERNATIONAL.)

Unlabelled: What's known on the subject? and What does the study add? It is known that the majority (80%) of solid renal masses are malignant. Most of the literature suggests that smaller tumour size is associated with a higher incidence of benign disease. We have confirmed that decreased tumour size is associated with benign disease, particularly for lesions <2 cm. Once radiologically apparent angiomyolipomas are excluded, the incidence of benign disease with small renal masses is lower than reported in the literature (11%). Furthermore, we have shown that small renal masses in females have a higher association with benign disease. Patient age and tumour location were not predictive of benign histology. We have also stratified our risks not only for benign disease but also for clinically indolent renal cancers to help physicians counsel patients with regard to managing these solid renal masses., Objective: • To determine the clinical predictors of benign disease in patients with solitary solid renal masses., Patients and Methods: • Pathology reports of patients who underwent radical or partial nephrectomy at two hospitals from 1998 to 2008 were reviewed. • Only patients with solitary solid unilateral renal masses were included. • Predictors of malignancy risk were assessed with univariate and multivariate logistic regression analysis., Results: • A total of 592 patients with a mean (sd) age of 60 (13) years were included, 38% of whom were women. Radical and partial nephrectomy was performed in 66% and 34% of patients, respectively. • Renal masses were equally distributed on the right and left sides (49% vs 51%, P= 0.84). Masses were more commonly located in the upper and lower poles than in the mid pole (40.8% vs 38.7% vs 20.5%, respectively). • The mean tumour size was larger in patients who underwent radical compared with partial nephrectomy (6.8 cm vs 2.9 cm, P < 0.001). The rate of benign disease in our overall population was 9.5%. • On univariate and multivariate analysis, only a renal mass size <2 cm and female gender were predictive of benign disease. On further analysis the magnitude of this effect was found to be additive., Conclusions: • Renal masses <2 cm and female gender were associated with a higher probability of benign disease. • Patient age and tumour location were not predictive of benign disease., (© 2012 THE AUTHORS. BJU INTERNATIONAL © 2012 BJU INTERNATIONAL.)

Unlabelled: Study Type - Prognosis (cohort) Level of Evidence 2a. What's known on the subject? and What does the study add? Radical cystectomy with pelvic lymph node dissection is recognized as the standard of care for carcinoma invading bladder muscle and for refractory non-muscle-invasive bladder cancer. Owing to high recurrence and progression rates, a two-pronged strict surveillance regimen, consisting of both functional and oncological follow-up, has been advocated. It is also well recognized that more aggressive tumours with extravesical disease and node-positive disease recur more frequently and have worse outcomes. This study adds to the scant body of literature available regarding surveillance strategies after radical cystectomy for bladder cancer. In the absence of any solid evidence supporting the role of strict surveillance regimens, this extensive examination of recurrence patterns in a large multi-institutional project lends further support to the continued use of risk-stratified follow-up and emphasizes the need for earlier strict surveillance in patients with extravesical and node-positive disease., Objectives: • To review our data on recurrence patterns after radical cystectomy (RC) for bladder cancer (BC). • To establish appropriate surveillance protocols., Patients and Methods: • We collected and pooled data from a database of 2287 patients who had undergone RC for BC between 1998 and 2008 in eight different Canadian academic centres. • Of the 2287 patients, 1890 had complete recurrence information and form the basis of the present study., Results: • A total of 825 patients (43.6%) developed recurrence. • According to location, 48.6% of recurrent tumours were distant, 25.2% pelvic, 14.5% retroperitoneal and 11.8% to multiple regions such as pelvic and retroperitoneal or pelvic and distant. • The median (range) time to recurrence for the entire population was 10.1 (1-192) months with 90 and 97% of all recurrences within 2 and 5 years of RC, respectively. • According to stage, pTxN+ tumours were more likely to recur than ≥pT3N0 tumours and ≤pT2N0 tumours (5-yr RFS 25% vs. 44% vs. 66% respectively, P < 0.001). Similarly, pTxN+ tumours had a shorter median time to recurrence (9 months, range 1-72 months) than ≥pT3N0 tumours (10 months, range 1-70 months) or ≤pT2N0 tumours (14 months, range 1-192 months, P < 0.001)., Conclusions: • Differences in recurrence patterns after RC suggest the need for varied follow-up protocols for each group. • We propose a stage-based protocol for surveillance of patients with BC treated with RC that captures most recurrences while limiting over-investigation., (© 2012 BJU INTERNATIONAL.)

Unlabelled: It is well established that upper tract urothelial carcinoma is a rare cancer with an aggressive course. Currently, radical nephroureterectomy with bladder cuff excision remains the standard of care in the treatment of these tumours. Previous studies demonstrate that stage, grade and lymphovascular invasion have prognostic significance on recurrence and outcome whereas the prognostic impact of tumour location remains unclear. This study provides an accurate analysis of the impact of tumour location and multifocality on prognosis in patients with upper tract urothelial carcinoma following nephroureterectomy with bladder cuff excision. Ureteral tumour location, particularly when associated with multifocal disease in the renal pelvis, is significantly associated with an increased risk of disease recurrence and cancer-specific death after surgery., Objective: To examine the significance of ureteral and renal pelvic location of upper tract urothelial carcinoma in a large multi-institutional study., Materials and Methods: We collected and pooled a database of 637 patients with upper tract urothelial carcinoma who underwent radical nephroureterectomy and bladder cuff excision in nine international academic centres. Univariate and multivariate models examined the effect of tumour location on recurrence-free survival (RFS) and cancer-specific survival (CSS) rates. Collected variables included age, gender, race, presence of lymphovascular invasion, concomitant carcinoma in situ, pathological stage, lymph node dissection and type of surgery (open vs laparoscopic)., Results: Anatomically, 34% of tumours were ureteral, 59% were renal pelvic and 7% were multifocal. Median follow-up for patients alive was 42 months (interquartile range: 19-76). Race, type of surgery, pathological stage and presence of lymphovascular invasion were significantly different across the three subgroups of patients (all P values <0.05). Age, gender, grade, presence of concomitant carcinoma in situ and follow-up duration were similar among the three subgroups. On multivariable Cox regression analyses, ureteral tumour location was an independent predictor of worse RFS (hazard ratio 2.1, P = 0.006) and CSS (hazard ratio 2.0, P = 0.027). When associated with renal pelvic disease, ureteral location was an even stronger independent predictor of worse RFS (hazard ratio 4.6, P < 0.001) and CSS (hazard ratio 4.0, P < 0.001)., Conclusion: Ureteral tumour location, particularly in association with multifocal disease in the renal pelvis, is an independent prognostic factor for higher disease recurrence and cancer-specific mortality., (© 2011 BJU INTERNATIONAL.)

Objective: To evaluate the prognostic role of ECOG Performance status (ECOG-PS) in a large multi-institutional international cohort of patients treated with radical nephroureterectomy for upper tract urothelial carcinoma., Materials and Methods: Data of 427 patients treated with radical nephroureterectomy at five international institutions in Asia, Europe and Northern America were collected retrospectively from 1987 to 2008. Logistic and Cox regression models were used for univariable and multivariable analyses., Results: ECOG-PS was 0 in 272 of 427 (64%) patients. The median follow-up of the whole cohort was 32 months. The five-year recurrence-free (RFS), cancer-specific (CSS) and overall (OS) survival estimates were 71.7%, 74.9% and 68.5%, respectively, in patients with ECOG-PS 0 compared with 60.1%, 67.8%, and 51.4% respectively, in patients with ECOG-PS ≥1 (P value 0.08 for RFS, 0.43 for CSS, and <0.001 for OS, respectively). On multivariable Cox regression analyses, ECOG-PS was not an independent predictor of either RFS (hazard ratio 1.4; P = 0.107) or CSS (hazard ratio 1.2; P = 0.426) but was an independent predictor of OS (hazard ratio 1.5; P = 0.03)., Conclusions: In this large multicentre international study, ECOG-PS was not significantly associated with RFS and CSS. Conversely we find a strong association with survival 1-month after surgery and OS. Further research is needed to ascertain the additive prognostic role of ECOG-PS in well-designed prospective multicentre studies., (© 2011 THE AUTHORS. BJU INTERNATIONAL © 2011 BJU INTERNATIONAL.)

Objective: To assess outcome in patients with T1 high-grade (T1HG) bladder cancer treated at a single academic institution and to determine the prognostic factors that can help in counselling patients towards early cystectomy., Patients and Methods: Records of 2570 patients with bladder cancer treated from 1995 to 2005 were reviewed. Only patients diagnosed with T1HG disease were included in the analysis. Collected variables included various clinicopathological parameters, use of statins, smoking, as well as dates of recurrence, progression, radical cystectomy and death. Recurrence-free survival (RFS) and worsening-free survival (WFS) were analyzed. Multivariate Cox proportional regression analysis was employed to verify the prognostic significance of various variables., Results: In total, 278 (10.8%) patients were identified as having T1HG disease on transurethral resection. 66% of patients who recurred, and 36.3% developed stage progression after a median (range) follow-up of 3 (0.1-15.4) years. 30% patients who underwent radical cystectomy, and 9% were dead of disease. The 5-year RFS and WFS rates were 26.6% and 49.4%, respectively. On multivariate analysis, only non-trigonal tumour location, restaging transurethral resection, history of previous carcinoma not invading bladder muscle and adjuvant bacille Calmette-Guérin (BCG) therapy were significantly associated with prolonged RFS, whereas papillary tumour architecture, history of previous carcinoma not invading bladder muscle and adjuvant BCG therapy were significantly associated with prolonged WFS., Conclusions: Patients with T1HG bladder cancer are at a significant risk of progression and death from disease. Primary tumours, sessile architecture and trigonal location are factors associated with a worse outcome and may be used to counsel patients towards early cystectomy., (© 2011 THE AUTHORS. BJU INTERNATIONAL © 2011 BJU INTERNATIONAL.)

Objective: • To describe a multicentre experience with preoperative platinum-based chemotherapy before radical nephroureterectomy (RNU) in patients with upper tract urothelial carcinoma (UTUC) with loco-regional nodal metastases., Patients and Methods: • We identified 313 patients from the UTUC Collaboration (over 1200 patients), who underwent RNU with concomitant retroperitoneal lymph node dissection between 1990 and 2007 and met the inclusion criteria for one of three groups. • Group 1 comprised patients who received chemotherapy before RNU because of biopsy-proven loco-regional nodal metastases. • Group 2 consisted of patients who underwent primary RNU and were found to have metastatic nodal disease on final pathological review (node-positive). • Group 3 comprised a comparative cohort of patients treated with primary RNU for invasive or locally advanced (pT2/pT4) node-negative (N0) UTUC., Results: • Groups 1, 2 and 3 included 18, 120 and 175 patients, respectively. The 5-year disease-free survival rates were 49%, 30% and 64%, whereas the 5-year cancer-specific survival rates were 44%, 36% and 69% in groups 1, 2 and 3, respectively. • In group 1, on final pathological evaluation, nine patients were pN0, six patients were pT0 and five patients had pT0N0 disease. Kaplan-Meier survival analyses showed similar recurrence and survival rates in group 1 compared with group 3 (P= 0.14 and P= 0.06, respectively). • Meanwhile, group 2 had significantly lower disease-free and cancer-specific survival rates compared with group 3 (P < 0.001 and P < 0.001, respectively) and compared with group 1 (P= 0.04 and P= 0.06, respectively)., Conclusions: • Preoperative chemotherapy followed by aggressive surgical consolidation may yield favourable oncological outcomes in patients with UTUC with loco-regional nodal metastases. • These data support further evaluation of neoadjuvant systemic therapy in patients at risk for locally advanced UTUC., (© 2011 THE AUTHORS. BJU INTERNATIONAL © 2011 BJU INTERNATIONAL.)

Objective: •To assess the impact of differences in ethnicity on clinico-pathological characteristics and outcomes of patients with upper urinary tract urothelial carcinoma (UTUC) in a large multi-center series of patients treated with radical nephroureterectomy (RNU)., Materials and Methods: •We retrospectively collected the data of 2163 patients treated with RNU at 20 academic centres in America, Asia, and Europe. •Univariable and multivariable Cox regression models addressed recurrence-free survival (RFS) and cancer-specific survival (CSS)., Results: •In all, 1794 (83%) patients were Caucasian and 369 (17%) were Japanese. All the main clinical and pathological features were significantly different between the two ethnicities. •The median follow-up of the whole cohort was 36 months. At last follow-up, 554 patients (26%) developed disease recurrence and 461 (21%) were dead from UTUC. •The 5-year RFS and CSS estimates were 71.5% and 74.2%, respectively, for Caucasian patients compared with 68.8% and 75.4%, respectively, for Japanese patients. •On univariable Cox regression analyses, ethnicity was not significantly associated with either RFS (P= 0.231) or CSS (P= 0.752). •On multivariable Cox regression analyses that adjusted for the effects of age, gender, surgical type, T stage, grade, tumour architecture, presence of concomitant carcinoma in situ, lymphovascular invasion, tumour necrosis, and lymph node status, ethnicity was not associated with either RFS (hazard ratio [HR] 1.1; P= 0.447) or CSS (HR 1.0; P= 0.908)., Conclusions: •There were major differences in the clinico-pathological characteristics of Caucasian and Japanese patients. •However, RFS and CSS probabilities were not affected by ethnicity and race was not an independent predictor of either recurrence or cancer-related death., (© 2011 THE AUTHORS; BJU INTERNATIONAL © 2011 BJU INTERNATIONAL.)

Objective: • To investigate among general practitioners (GPs) their level of awareness and indications for urological consultations in patients treated with 5α-reductase inhibitors (5ARIs)., Subjects and Methods: • We conducted a survey of GPs in Quebec. • Questions covered GPs' preferred benign prostatic hyperplasia (BPH) management, knowledge of 5ARIs, their role in prostate cancer prevention, and triggers for urology consultation., Results: • Of the surveys mailed, 599 were returned (15.7% response rate). • Therapy with 5ARIs was initiated by GPs in 34.3%, with 20% and 12% preferring 5ARIs alone and combined with an α-blocker as first-line therapy for BPH, respectively. • Once on therapy, 74% did not refer to a urologist if the PSA level did not decline after 6-12 months. • Finally, 40.7% would not advocate 5ARI chemoprevention for prostate cancer, regardless of risk reduction. • Findings were not associated with GP gender, experience or geographic location of practice (urban versus rural)., Conclusions: • There was a preference amongst GP to use α-blockers over 5ARIs for BPH and hesitancy to use them in prostate cancer chemoprevention. • There is a lack of awareness of 5ARI effects on PSA kinetics and a reluctance to refer to a urologist. • Further education in Quebec is needed about 5ARIs to optimize their usage and avoid delaying cancer detection., (© 2010 THE AUTHORS. BJU INTERNATIONAL © 2010 BJU INTERNATIONAL.)

Objective: • To stratify risk of pathological (p) T2N0 urothelial carcinoma of the bladder after radical cystectomy (RC) based on pathological factors to facilitate the development of adjuvant therapy trials for high-risk patients., Patients and Methods: • The study comprised 707 patients from a database of patients with pT2N0 urothelial carcinoma of the bladder who had undergone RC and not received perioperative chemotherapy. • The effect of residual pT-stage at RC, age, grade, lymphovascular invasion and number of lymph nodes removed on recurrence-free survival was evaluated using Cox regression analyses. A weighted prognostic model was devised with significant variables., Results: • The median follow up was 60.9 months. In multivariable analyses, residual disease at RC (pT2a: hazard ratio (HR) 1.740, P = 0.03; for pT2b: HR 3.075, P < 0.001; both compared with

Unlabelled: Study Type -Therapy (case series)., Level of Evidence: 4., Objective: To evaluate data obtained from a large, multi-institutional, contemporary series of patients who underwent radical cystectomy (RC) in a universal healthcare system aiming to assess outcome and identify novel prognostic variables., Materials and Methods: Data were collected and pooled from 2287 patients treated with RC between 1998 and 2008 by urological oncologists from eight Canadian academic centres. Collected variables included various clinicopathological parameters, recurrence and death. Survival and prognostic variables were analyzed using the Kaplan-Meier method and Cox regression analysis., Results: The median age of patients was 68 years with a mean (median) follow-up time of 35 (29) months. The 30, 60 and 90-day postoperative mortality rates were 1.3%, 2.6% and 3.2%, respectively. The 5-year overall, recurrence-free and cancer-specific survival was 57%, 48% and 67%, respectively, with a local recurrence rate of 6%. Pathological stage distribution was

Objective: • To compare oncological outcomes in patients undergoing open radical nephroureterectomy (ONU) with those in patients undergoing laparoscopic radical nephroureterectomy (LNU)., Patients and Methods: • A total of 773 patients underwent radical nephroureterectomy at nine centres worldwide; 703 patients underwent ONU and 70 underwent LNU. • Demographic, perioperative and oncological outcome data were collected retrospectively. • Statistical analysis of data was performed using chi-squared, Mann-Whitney U- and log-rank tests, and Cox regression analyses. • The median (interquartile range) follow-up for the cohort was 34 (15-65) months., Results: • The two groups were well matched for tumour stage, presence of lymphovascular invasion (LVI) and concomitant carcinoma in situ (CIS). • There were more high-grade tumours (77.1% vs. 56.3%; P < 0.001) but fewer lymph node positive patients (2.9% vs. 6.8%; P= 0.041) in the LNU group. • Estimated 5-year recurrence-free survival (RFS) was 73.7% and 63.4% for the ONU and LNU groups, respectively (P= 0.124) and estimated 5-year cancer-specific survival (CSS) was 75.4% and 75.2% for the ONU and LNU groups, respectively (P= 0.897). • On multivariable analyses, which included age, gender, race, previous endoscopic treatment for bladder cancer, technique for distal ureter management, tumour location, pathological stage, grade, lymph node status, LVI and concomitant CIS, the procedure type (LNU vs. ONU) was not predictive of RFS (Hazard ratio [HR] 0.80; P= 0.534) or CSS (HR 0.96; P= 0.907)., Conclusion: • The present study is the second large, independent, multicentre cohort to show oncological equivalence between ONU and LNU for well selected patients with upper urinary tract urothelial cancer, and the first to suggest parity for the techniques in patients with unfavourable disease., (© 2010 THE AUTHORS. BJU INTERNATIONAL © 2010 BJU INTERNATIONAL.)

Objective: • To compare the clinical and pathologic stage among a large, multi-institutional series of patients undergoing radical and to determine the effect of stage discrepancy on outcomes., Patients and Methods: • Data was collected from nine centers and 3,393 patients with urothelial carcinoma of the bladder (UCB) treated with radical cystectomy and pelvic lymphadenectomy without neo-adjuvant chemotherapy. • A retrospective cohort design was used to assess the percentage of patients experiencing stage discrepancy and the impact of stage discrepancy on time to disease relapse and time to death from UCB., Results: • Clinical under staging occurred in 50% of patients and pathologic down staging occurred in 18% of patients. • Up staging to muscle invasive disease occurred in 45.9% (n = 592) of 1,291 patients with clinical ≤T1, including 30.6% of patients with Tis only at transurethral resection. • Of the 3,166 patients with clinically organ confined (OC) tumor stage, 1,357 (42.9%) were up staged to non-organ confined pathologic tumor stage. • Within each clinical stage stratum, patients who were clinically under staged had a higher probability of disease relapse or death from UCB compared to those who were same staged or down staged on pathologic examination (P < 0.05)., Conclusions: • We identified clinical under staging in half of the patients undergoing radical cystectomy for UCB. • Up staging resulted in a higher likelihood of disease progression and eventual death from UCB. • These findings should be considered when utilizing pre-operative risk-adapted strategies for selecting candidates for neoadjuvant chemotherapy., (© 2011 THE AUTHORS. BJU INTERNATIONAL © 2011 BJU INTERNATIONAL.)

Study Type: Therapy (case series) Level of Evidence 4 OBJECTIVE To evaluate our experience with urethral recurrences in patients treated by radical cystectomy(RC) and orthotopic neobladder urinary diversion for carcinoma of the bladder., Patients and Methods: We retrospectively reviewed the records of patients treated with RC and orthotopic urinary diversion between January 1980 and July 2004., Results: In all, 260 patients underwent RC with a Studer or Hautmann orthotopic urinary diversion; the median (range) follow-up was 5.1 (0-15.6) years. Six patients (2.3%) developed local recurrence of urothelial cancer (UC) within the urethra after this treatment. The median (range) time to presentation with recurrence after RC was 2.4 (0.7-3.6) years for pT1-4 UC. Recurrences were treated with various methods, including transurethral resection, urethrectomy with conversion of neobladder to continent catheterizable diversion, and chemotherapy. At the last follow-up, four of these six patients were alive without disease, one was alive with disease, and one had died from disease., Conclusions: In our experience, local recurrences involving the urethra are infrequent. Complete surgical excision can provide a good outcome. Neoadjuvant chemotherapy should be considered for recurrences with adverse clinicopathological features.

Objective: To gather a pooled database from six tertiary-care referral centres using salvage cryotherapy (SC) for locally recurrent prostate cancer, and develop a pretreatment nomogram allowing a prediction of the probability of biochemical failure after SC, based on pretreatment clinical variables., Patients and Methods: We retrospectively analysed 797 men treated at six tertiary-care referral centres with SC for locally recurrent disease after primary radiotherapy with curative intent. The median duration of follow-up from the time of SC to the date of last contact was 3.4 years. The primary study endpoint was biochemical failure, defined as a serum prostate-specific antigen (PSA) level after SC of >0.5 ng/mL., Results: Overall, the rate of biochemical failure was 66% with a median of 3.4 years of follow-up. A logistic regression model was used to predict biochemical failure. Covariates included serum PSA level at diagnosis, initial clinical T stage, and initial biopsy Gleason score. On the basis of these results, a pretreatment nomogram was developed which can be used to help select patients best suited for SC. Our pretreatment nomogram was internally validated using 500 bootstrap samples, with the concordance index of the model being 0.70., Conclusion: A pretreatment nomogram based on several diagnostic variables (serum PSA level at diagnosis, biopsy Gleason grade, and initial clinical T stage) was developed and might allow the selection of ideal candidates for SC.

Objective: To assess the impact of patient age on outcomes after radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC)., Patients and Methods: Data were collected on 1453 patients treated with RNU at 13 centres. Pathological slides were reviewed by dedicated genitourinary pathologists according to standardized criteria. Age at RNU was analysed both as a continuous and categorical variable (<50, n = 85; 50-59.9, n = 229; 60-69.9, n = 416; 70-79.9, n = 523; > or =80 years, n = 200). RESULTS Patients aged <50 years were less likely to have undergone previous ureteroscopy and to have a history of bladder cancer (P < or = 0.026). Advanced age was associated with infiltrative architecture and female gender (P < or = 0.003). Patients aged >70 years were less likely to undergo lymphadenectomy and to receive adjuvant chemotherapy (P < or = 0.026). In multivariable analyses, being older was associated with decreased all-cause (AC) survival (>60 years) and cancer-specific survival (CSS; >80 years) after controlling for the effects of standard pathological features (P < or = 0.006). However, addition of age did not improve the predictive accuracy of a base model that included standard pathological features for prediction of either disease recurrence, AC survival or CSS., Conclusions: Being older at the time of RNU was associated with decreased survival. This finding could be due to a change in the biological potential of the tumour cell, a decrease in the host's defence mechanisms, or differences in care patterns. Further work is needed to improve our understanding of UTUC outcomes in this growing segment of the population and to develop strategies to improve cancer control in the elderly.

Objective: To externally validate the prognostic value of lymphovascular invasion (LVI) in a large international cohort of patients treated with radical cystectomy (RC) for urothelial carcinoma of the bladder (UCB)., Patients and Methods: We collected data from 4257 patients treated with RC and pelvic lymphadenectomy for UCB, without neoadjuvant chemotherapy, at 12 centres. LVI was defined as presence of nests of tumour cells within an endothelium-lined space., Results: LVI was detected in 1407 patients (33.1%); the proportion of LVI increased with advancing stage, higher grade, soft-tissue surgical margin involvement, and lymph node metastasis (P < 0.001 for all). In standard multivariate models, LVI was associated with both disease recurrence (hazard ratio 1.43, P < 0.001) and cancer-specific mortality (1.45, P < 0.001). In the entire cohort, adding LVI to a base model that included standard features improved only minimally its predictive accuracy for both recurrence and cancer-specific mortality (by 1.1% and 1.2%, respectively). In 3122 patients with negative lymph nodes, LVI remained independently associated with and improved the predictive accuracy of the standard predictors for recurrence (hazard ratio 1.68, P < 0.001; +2.3%) and cancer-specific mortality (1.70, P < 0.001; +2.4%). By contrast, in 1071 node-positive patients, LVI only marginally improved the prediction of cancer-specific recurrence (hazard ratio 1.20, P < 0.001; +0.2%) and survival (1.23, P < 0.001; +0.5%)., Conclusions: LVI is strongly associated with clinical outcome in node-negative patients treated with RC. The assessment of LVI might help to identify patients who could benefit from adjuvant therapy after RC. After confirmation in different populations, LVI should be included in the staging of UCB.

Objective: To evaluate our experience with surgical resection of renal cell carcinoma (RCC) with inferior vena cava (IVC) involvement and examine the relationship between prognosis and tumour extent., Patients and Methods: A retrospective review of nephrectomy performed between 1985 and 2005 identified 50 patients presenting with tumour thrombus extension into the IVC. Clinical characteristics and outcome were evaluated., Results: Of the 50 patients evaluated, 7, 26, 10 and 7 presented with level I, II, III and IV thrombus, respectively. Major postoperative complications occurred in 16% of patients. Local or distant failure occurred in 25 (64%) patients. The mean time to recurrence was 10 months. Only supra-diaphragmatic extension of the tumour thrombus was predictive of disease recurrence., Conclusion: Locally advanced RCC with IVC thrombus remains associated with significant local and distant failure rate. The level of thrombus extension is significantly associated with disease recurrence. Effective adjuvant therapy is needed to improve outcome in this patient population.

Objective: To evaluate the ability of the five-item version of the International Index of Erectile Function (IIEF-5) to diagnose the vascular aetiology and severity of erectile dysfunction (ED), and to compare it with pharmacological testing and duplex Doppler ultrasonography, as such questionnaires are widely used by the pharmaceutical industry to categorize the severity of ED and to assess the efficacy of drug therapy., Patients and Methods: In all, 80 patients (mean age 45.2 years, sd 14.0; mean duration of ED 3.5 years) were reviewed by an examiner unaware of their IIEF scores during testing. Penile blood flow was assessed in each patient after an intracavernosal injection with prostaglandin-E1 (10 micro g), with self-stimulation in privacy. The peak systolic velocity, end diastolic velocity and resistive index were measured for the vascular diagnosis. Visual ratings of erectile responses were also used for analysis., Results: Of the 80 patients, 30 had a normal vascular response, 38 arterial insufficiency and 12 were diagnosed with venous leakage. There was no significant difference in the IIEF scores among patients with a normal vascular response, arterial insufficiency or venous leakage. Analysis of visual ratings of erections showed no difference in IIEF scores among the different groups of patients., Conclusion: The IIEF was designed and developed specifically for assessing and evaluating sexual function in clinical trials. However, as shown here, the IIEF cannot and should not be used as a tool to diagnose or compare specific vascular causes of ED.