Search

Purpose: The impact of sex hormones on cancer immunotherapy remains controversial. Androgens, via the androgen receptor (AR), may impact the success of immune checkpoint blockade. This study characterizes AR and programmed death ligand-1 (PD-L1) expression in bladder tumors with long clinical follow-up., Methods: AR and PD-L1 expression was analyzed using immunohistochemistry on 143 transurethral resection (TUR) and 203 radical cystectomy (RC) specimens. Descriptive statistics and survival analyses assessed the relationship of AR and PD-L1 staining with clinical outcomes of tumor recurrence, progression, and overall survival., Results: AR expression was observed in a higher proportion of TUR than RC specimens (59% vs 35%, p < 0.001). High immune cell (IC) PD-L1 expression was associated with higher stage and grade. Patients with the combination of an absence of AR expression and the highest (> 10%) IC PD-L1 expression in TUR tumors had an increased risk of recurrence and progression. In RC specimens, the expression of AR increased the risk of local recurrence (adjusted hazard ratio (HR) 2.09, 95% CI 0.98-4.45), which was even higher among patients who also had IC PD-L1 expression (HR 4.16, 95% CI 1.28-13.52). For 28 paired metastatic lymph nodes among RC patients, tumor cell PD-L1 expression was significantly correlated (r = 0.48, p = 0.01), while no relationship with IC PD-L1 expression was observed., Conclusions: The expression of AR and its relationship to clinical outcomes appears to vary between non-muscle invasive and muscle-invasive bladder cancer. Our results support the role of IC PD-L1 expression as an independent risk factor for bladder cancer outcomes.

Introduction: The "trifecta" is a summary measure of outcome after partial nephrectomy (PN) that encompasses three parameters: negative surgical margin, ≤ 10% decrease in post-operative estimated glomerular filtration rate (eGFR) and absence of urological complications. We assessed trifecta rates in patients undergoing open (OPN), laparoscopic (LPN), and robotic PN (RPN) for a clinical T1 renal mass (≤ 7 cm)., Methods: Clinical and pathologic parameters were extracted from the prospectively maintained Canadian Kidney Cancer Information System for patients treated between January 2011 and October 2018. Comparisons between groups were made using Kruskal-Wallis test for continuous variables and Chi-squared independence test for categorical variables. Multivariable analysis was performed to identify predictors of each component of the trifecta and the trifecta itself., Results: Of 1708 total patients, 746 underwent OPN, 678 LPN, and 284 RPN for a T1 renal mass. A 'trifecta' was achieved in 53% OPN, 52% LPN and 47% RPN (p = 0.194). On multivariable analysis, OPN and LPN were associated with less frequent post-operative decline in eGFR and more frequent trifecta when compared to RPN, but there was no difference between OPN and LPN. OPN also predicted a higher rate of negative margins compared to RPN but not LPN., Conclusion: After correction for confounding variables, OPN and LPN were more likely than RPN to achieve the trifecta, which appeared to be due primarily to loss of renal function. No difference was observed between OPN and LPN. Analyses were limited by the lack of nephrometry score.

Purpose: We evaluated whether an increased body-mass index (BMI) and decreased physical activity increase the risk of locally advanced or high-risk prostate cancer (PCa) at radical prostatectomy (RP), and treatment failure after surgery., Methods: Data were collected from the PROCURE Biobank, a prospective cohort of patients with localized PCa undergoing RP in four academic centers in Québec between 2006 and 2013. Treatment failure was defined as biochemical recurrence and/or initiation of secondary, non-adjuvant therapy, and analyzed using the Kaplan-Meier method, log-rank tests, and Cox proportional-hazards models. Uni- and multivariate (ordered) logistic regression was used for time-independent variables., Results: 1813 patients were included. Median follow-up time was 69 months. Patients who reported a lower BMI were generally older, of Asian descent, and physically more active (p < 0.05). Younger, black, and overweight/obese patients reported less physical activity (p < 0.05). In multivariate analyses, a higher BMI increased the risk for locally advanced, high-risk PCa (defined as a pT3, N1 and/or Gleason 8-10 tumor; odds ratio 1.33, p < 0.001), but increased physical activity did not predict high-risk disease (odds ratio 0.84, p = 0.39). Patients with a higher BMI also had a larger prostate at surgery (odds ratio 1.13, p = 0.03). BMI and physical activity were not associated with positive surgical margins or time to treatment failure (p > 0.05)., Conclusions: BMI was an independent predictor for locally advanced, high-risk disease in this cohort of PCa patients undergoing RP, but was unrelated to treatment failure. Physical activity was not related to locally advanced, high-risk PCa or treatment failure.

Purpose: To evaluate the impact of concomitant carcinoma in situ (CIS) on upstaging and outcome of patients treated with radical cystectomy with pelvic lymph node dissection., Methods: We collected and pooled a database of 1,968 patients who have undergone radical cystectomy between 1998 and 2008 in eight academic centers across Canada. Collected variables included patient's age, gender, tumor grade, histology and the presence of concomitant CIS with either cTa-1 or cT2 disease, dates of recurrence and death., Results: In the presence of concomitant CIS, upstaging following radical cystectomy occurred in 48 and 55 % of patients with cTa-1 and cT2 disease, respectively. On univariate analysis, the presence of concomitant CIS with cT2 disease was associated with upstaging (p < 0.0001), and the presence of concomitant CIS with cTa-1 disease was also associated with upstaging but did not reach statistical significance (p = 0.0526). On multivariate analyses, the presence of concomitant CIS with either cTa-1 or cT2 tumors was independently prognostic of disease upstaging (p = 0.0001 and 0.0186, respectively). However, on multivariate analysis that incorporates pathologic stage, concomitant CIS was not significantly associated with worse overall, recurrence-free or disease-specific survival., Conclusion: These results demonstrate that while the presence of concomitant CIS on cystectomy specimens does not independently affect outcomes, its presence is significantly predictive of a higher rate of upstaging at radical cystectomy.

Purpose: To analyze time in relation to biochemical recurrence (BCR) and antiandrogen therapy (ADT) in patients with node metastasis at retropubic prostatectomy (RRP) and to identify prognostic factors of BCR- and ADT-free survival., Methods: Positive node patients at RRP and extended pelvic lymph node dissection (ePLND) were recruited retrospectively. Neoadjuvant and adjuvant therapy were exclusion criteria. BR was defined as PSA ≥ 0.3 ng/ml or the beginning of salvage radiotherapy or, ADT., Results: Between 1995 and 2008, 70 node-positive patients after RRP were followed without ADT. Overall, BCR-free survival was 77.9% at 2 years and 29.7% at 8 years. The median time to BCR was 59.2 months for patients with only one node compared to 27.7 months for those with ≥2 nodes. The number of positive nodes was the only independent predictor of BCR in Cox regression multivariable analysis. ADT-free survival was 78% at 2 years and 39% at 8 years. The median time to ADT for patients with only one positive node was 115 months, and the 5 years ADT-free survival was 68.8%. Gleason score and the number of positive nodes were the only independent prognostic factors of time to ADT in the Cox regression multivariable analysis., Conclusions: The prognosis of patients with positive nodes after RRP and ePNLD is good in terms of BCR- and ADT-free survival. After 8 years, 29.7% were still free from BCR, and 39% did not receive ADT. The number of positive nodes was the most important predictor of BCR- and ADT-free survival.

Purpose: To compare clinical and pathologic outcomes of radical cystectomy for muscle invasive bladder cancer in relation to prior history of non-invasive urothelial carcinoma., Materials and Methods: Retrospective data collected from 1,150 patients managed by radical cystectomy for urothelial carcinoma of the bladder from the Canadian Bladder Cancer Network were analysed. Patients with clinical stage T2 or more were included and divided into two groups: (Group 1) patients with prior history of non-invasive urothelial carcinoma (N = 365) and (Group 2) patients with clinical muscle invasive cancer de novo (N = 785). Variables analysed included patient age, gender, pathologic stage, adjuvant chemotherapy, recurrence and mortality., Results: Both groups were nearly equal in mean age and gender distribution, with mean ages of 67.2 and 66.7 years, and 79.7 and 79.5%, respectively (P = 0.4 and 0.9, respectively). The presence of preoperative hydronephrosis was 20.8 and 32.6% (P = 0.0007) for groups 1 and 2, respectively. The rate of higher pathological stage (T3 or T4) was 36.3 and 58% (P < 0.0001), positive lymph nodes were 20.1 and 28.8% (P = 0.002), and lymphovascular invasion was 31.7 and 46.2% (P = 0.0001) for groups 1 and 2, respectively. The rate of adjuvant chemotherapy was 15.5 and 23.3% (P = 0.002) for groups 1 and 2, respectively. None of the sampled patients received neoadjuvant chemotherapy. The overall survival (OS) and disease-specific survival (DSS) rates at 5 years were 62 and 70% for group 1 and 51 and 60% for group 2, respectively, while at 10 years, OS and DSS were 46 and 66% for group 1 and 35 and 49% for group 2, respectively (P = 0.0001 and 0.0002, respectively). Using multivariate analysis examining factors affecting recurrence and survival, we found that previous non-invasive bladder tumour history was associated with a significantly reduced risk of mortality and recurrence (Hazard ratio of 0.7 for all risks, P = 0.0002)., Conclusion: Our retrospective study suggests that patients with non-invasive urothelial carcinoma of the bladder that progress to muscle invasion and require radical cystectomy appear to have better pathologic and clinical outcome than patients presenting with clinical muscle invasive disease de novo.

Aim: To evaluate the clinical outcome of high-risk prostate cancer (PC) treated by radical prostatectomy (RP) according to risk factors., Methods: Patients with stage cT1-T3 PC were stratified in high and low/intermediate risk groups using D'Amico's criteria: PSA>or=20 ng/ml or Gleason score>or=8 or clinical stage>or=T2c. The Kaplan Meier and Log rank test were used to generate estimates of biochemical free-survival (BFS) and PC specific mortality (PCSM)., Results: We analysed 1,109 patients with a median age of 64.1 years, a mean PSA of 12.8 and a median follow-up of 8.18 years (max. 17.5 years). Overall PSA failures (PSAF) were observed in 23.4%, mortality by all causes in 11.4% and PCSM in 2.9%. The 10-year BFS of the 290 high-risk was 45 versus 75.5% for low/intermediate risk patients and the 10-year PCSM was 10.3 versus 1.4%, respectively. Of the 290 high-risk PC, 25% had organ-confined disease at surgery with 28% PSAF compared to 55% PSAF for non-organ-confined PC irrespective of nodal status. High-risk patients with 1 or>or=2 high risk criteria had 2.6 and 3.86 times increased risk of PSAF compared to low/intermediate risk. Ten-year PCSM for PC individual risk criteria was 4.5% for PSA>or=20, 9.2% for stage>or=T2c and 18.2% for Gleason>or=8., Conclusion: Patients with high-risk PC treated by RP by experienced surgeons can have a favourable long-term survival. Further substratification should take into account the variable prognostic implication of the different individual risk factors.