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Objectives: To evaluate the five-tier Gleason grade group (GG) scoring of prostate cancers adopted by the International Society of Urology Pathology (ISUP) in 2014, and to propose modifications to optimize its performance., Patients and Methods: Data were obtained from PROCURE, a prospective cohort of patients with localized prostate cancer undergoing radical prostatectomy in Québec, 2006-2013. Surgical specimens were evaluated by genitourinary pathologists using 2014 ISUP criteria. Treatment failure was defined as biochemical recurrence and/or initiation of secondary, non-adjuvant therapy. Analyses were conducted using Kaplan-Meier methods, log-rank tests, Cox proportional hazards models and Harrell's concordance indices., Results: A total of 1 917 patients were included, with a median follow-up of 69 months. The 5-year treatment failure rates were 9.6%, 23.5%, 43.1%, 52.6% and 84.3% in GG1-5, respectively (P < 0.001 when comparing GG2 with GG3). Treatment failure rates for patients in GG2 and GG3 with tertiary Gleason 5 pattern were higher than patients in the same group without a tertiary pattern (P < 0.001), but were similar to rates for patients in GGs 3 or 4 without a tertiary pattern (P > 0.3). Primary Gleason pattern (4/5) predicted treatment failure in GG5 (5-year failure rates 82.3% vs 97.1%, respectively; P = 0.001). The five-tier GG system had greater accuracy as a prognostic indicator compared with the four-tier system (Harrell's concordance index 0.716 vs 0.676). When upgrading patients in GG2/3 with tertiary Gleason 5 pattern to patients in GG3/4, and separating patients in GG5 by primary Gleason pattern, the Harrell's concordance index increased to 0.730., Conclusion: The five-tier GG system increased accuracy for predicting treatment failure compared with the previous grading systems, but can be further improved., (© 2018 The Authors BJU International © 2018 BJU International Published by John Wiley & Sons Ltd.)

Objectives: To determine the clinical performance of the urinary prostate cancer antigen 3 (PCA3) test to predict the risk of Gleason grade re-classification amongst men receiving a 5α-reductase inhibitor (5ARI) during active surveillance (AS) for prostate cancer., Patients and Methods: Patients with low-risk prostate cancer were enrolled in a prospective Phase II study of AS complemented with prescription of a 5ARI. A repeat biopsy was taken within the first year and annually according to physician and patient preference. In all, 90 patients had urine collected after digital rectal examination of the prostate before the first repeat biopsy. The PCA3 test was performed in a blinded manner at a central laboratory., Results: Using a PCA3-test score threshold of 35, there was a significant difference (P < 0.001) in the risk of being diagnosed with Gleason ≥7 cancer during a median of 7 years of follow-up. Adjusted Cox regression and Kaplan-Meier analyses also showed a significantly higher risk of upgrading to Gleason ≥7 during follow-up for those with a higher PCA3-test score., Conclusion: The urinary PCA3 test predicted Gleason grade re-classification amongst patients receiving a 5ARI during AS for low-risk prostate cancer., (© 2017 The Authors BJU International © 2017 BJU International Published by John Wiley & Sons Ltd.)

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: 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: 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

Unlabelled: Study Type - Prognosis (case series)., Level of Evidence: 4 OBJECTIVE: To determine whether the expression of cyclo-oxygenase (COX)-2 has an influence on survival and on the response to chemotherapy in invasive bladder cancer., Patients and Methods: A population of 266 patients from a tertiary university centre with carcinoma invading bladder muscle without evidence of metastasis at time of cystectomy was analyzed retrospectively. COX-2 expression was evaluated immunohistochemically with a monoclonal anti-COX-2 antibody. All pertinent clinical and pathological parameters were reviewed and correlated with risk factors influencing outcome, including disease-specific and overall survival, as well as COX-2 expression. Immunoreactivity was categorized as positive if COX-2 staining was present in >5% tumour cells., Results: The expression of COX-2 was not influenced by tumour stage, grade or nodal status, nor any other parameters. The risk factors that influenced disease-specific survival in carcinoma invading bladder muscle on multivariate analysis were lymph node status (hazards ratio, HR = 2.46 for N1, P = 0.001, HR = 2.90 for N2, P < 0.001, HR = 5.19 for N3, P = 0.012), use of neoadjuvant chemotherapy (HR = 3.54; P= 0.004) or adjuvant chemotherapy (HR = 0.57, P = 0.014) and COX-2 expression (HR = 0.64 if >5% cells had positive expression; P = 0.025). Kaplan-Meier analysis showed an increased disease-specific survival (P = 0.0063), as well as longer recurrence-free survival (P = 0.003), in patients with muscle-invasive bladder tumours expressing COX-2 in >5% of the cells. A tendency was also observed in a subgroup with positive nodes treated with adjuvant chemotherapy (P = 0.093)., Conclusions: The overexpression of COX-2 is associated with a better recurrence-free and disease-specific survival in a large cohort of 266 patients with carcinoma invading bladder muscle treated by cystectomy. A trend for increased disease-specific survival was also observed for patients with COX-2 overexpression and positive nodes who received adjuvant chemotherapy. Potential of COX-2 as a prognostic marker in bladder cancer should be considered., (© 2010 THE AUTHORS; BJU INTERNATIONAL © 2010 BJU INTERNATIONAL.)

Objective: To investigate the role of (18) F-fluorodeoxyglusose positron-emission tomography (FDG-PET), combined with computed tomography (CT) and forced diuresis, in the staging and follow-up of urothelial carcinoma (UC)., Patients and Methods: We recruited 44 patients with muscle-invasive urothelial bladder cancer (UBC) before radical cystectomy (RC), 19 under follow-up after RC and seven after systemic chemotherapy. For those who had RC, histopathology was used as the reference standard to compare the sensitivity and specificity of FDG-PET/CT and standard CT in detecting UBC and pelvic lymph node metastasis. Furthermore, 36 patients with ≥ 6 months of follow-up imaging were considered to describe the progression of UC and extrapelvic positive FDG-PET/CT images., Results: For the detection of primary UBC, FDG-PET/CT was slightly more sensitive than CT (85% vs 77%) but less specific (25% vs 50%). For the detection of pelvic node metastasis FDG-PET/CT was more sensitive than CT (57% vs 33%) with a specificity of 100% for both imaging techniques. In 20 patients, extrapelvic FDG-PET/CT images showed suspected disease at the first evaluation. UC progressed in nine of the 10 patients who had synchronous multiple PET-positive retroperitoneal or mediastinal lymph nodes, and in only two of the nine with unique hyperactive lesions in the lung. FDG-PET/CT also detected a pT1G3 UC of the renal pelvis and all bone metastases detected by bone scintigraphy., Conclusions: FDG-PET/CT could replace standard CT and bone scintigraphy in the presurgical staging and monitoring of patients with UC after surgery or chemotherapy., (© 2010 THE AUTHORS. JOURNAL COMPILATION © 2010 BJU INTERNATIONAL.)

Objective: To evaluate our experience with primary carcinomas of the female urethra, by analysing the impact of tumour variables and treatment on overall, disease-specific, local recurrence- and metastasis-free survival., Patients and Methods: Between 1958 and 1994, 72 women (median age 60 years, mean 59, range 21-84) with primary urethral carcinoma were identified. They were followed for a median (range) of 85 (0-384) months. The patients were stratified by stage, nodal status, histology, treatment, type of surgery, site of disease, year of diagnosis and smoking habit., Results: In a univariate analysis, stage, nodal status, type of surgery and site of the disease were important factors for survival and recurrence. In a multivariate analysis, primary stage, nodal status and site of disease were independent predictors of survival., Conclusion: Current modalities of treatment are ineffective for local control and survival; new treatment strategies are needed for female urethral cancers.