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Introduction: Rapid progress in diagnostics and therapeutics for the management of prostate cancer (PCa) have created areas where high-level evidence to guide practice is lacking. The Genitourinary Research Consortium (GURC) conducted its second Canadian consensus forum to address areas of controversy in the management of PCa and provide recommendations to guide treatment. Methods: A panel of PCa specialists discussed topics related to the management of PCa. The core scientific committee finalized the design, questions and the analysis of the consensus results. Attendees then voted to indicate their management choice regarding each statement/topic. Questions for voting were adapted from the 2019 Advanced Prostate Cancer Consensus Conference. The thresholds for agreement were set at ≥ 75% for ‘consensus agreement’, > 50% for “near-consensus”, and ≤ 50% for “no consensus”. Results: The panel was comprised of 29 PCa experts including urologists (n=12), medical oncologists (n= 12), and radiation oncologists (n= 5). Voting took place for 65 pre-determined questions and three ad hoc questions. Consensus was reached for 34 questions, spanning a variety of areas including biochemical recurrence, treatment of metastatic castration-sensitive PCa, management of non-metastatic and metastatic castration-resistant PCa, bone health, and molecular profiling. Conclusions: The consensus forum identified areas of consensus or near-consensus in more than half of the questions discussed. Areas of consensus typically aligned with available evidence, and areas of variability may indicate a lack of high-quality evidence and point to future opportunities for further research and education.

Androgen deprivation therapy (ADT) plays an important role in the contemporary management of prostate cancer (PCa) across various stages of the disease. While ADT remains a highly effective treatment for PCa, it is not curative, and its use is associated with significant adverse events that span across various organ systems.

Introduction: Metastatic bone disease in castrate-resistant prostate cancer risks significant morbidity, including symptomatic skeletal events. We estimated the healthcare resource costs of managing skeletal events. Methods: A retrospective chart review was conducted for patients who died from or were treated palliatively for metastatic castrate-resistant prostate cancer from 2006–2013 at Centre Hospitalier de l'Universite de Montreal (Montreal), Princess Margaret Cancer Centre (Toronto), or Vancouver General Hospital (Vancouver). Results: Of 393 patients, 275 (70%) experienced 833 events (85 per 100 patient-years), with a median (95% confidence interval) time (months) to first event of 17.6 (15.3, 21.7). The mean metastatic bone disease-related healthcare resource use cost (2014 Canadian dollars) estimate for patients without symptomatic skeletal events was $9550 and between $22 101 (observed) and $34 615 (adjusted) for patients with at least one event. Fewer patients in Montreal (55%) experienced events compared to Toronto (79%) or Vancouver (76%). Median time (months) to first event was longer in Montreal (25.0 [18.5, 32.6]) than in Toronto (14.6 [9.7, 16.8] or Vancouver (17.3 [14.8, 24.0]). More patients received bone-targeted therapy in Montreal (64%) and Toronto (60%) than in Vancouver (24%). Bone-targeted therapy was mostly administered every 3–4 weeks in Montreal and every 3–4 months in Toronto. Conclusions: Metastatic bone disease-related healthcare resource use costs for Canadian castrate-resistant prostate cancer patients are high. Symptomatic skeletal events occurred frequently, with the incremental cost of one or more events estimated between $12 641 and $25 120. Symptomatic skeletal event incidence and bone-targeted therapy use varied considerably between three Canadian uro-oncology centres. An important limitation is that only patients who died from prostate cancer were included, potentially overestimating costs.

Multiple new agents to treat metastatic castration-resistant prostate cancer (mCRPC) have become available in recent years; however, the appropriate timing and sequencing of these agents have yet to be elucidated. Until accurate biomarkers become available to allow more focused therapeutic targeting for this population, treatment selection for men with mCRPC will continue to be driven largely by close assessment of patient-related factors and symptoms. Pain, as the predominant symptom of mCRPC, is often the focus when assessing progression and the need for a change in treatment. A myriad of other symptoms, including fatigue, impact on activities of daily living, sleep, and lower urinary tract symptoms, also affect men with mCRPC, and assessment of the composite of these symptoms provides an earlier signal for the need to adjust treatment. A number of tools are available for assessing symptoms in patients with advanced prostate cancer, but they are not routinely used, given their complexity and length. A new simplified questionnaire is proposed for the assessment of symptoms, beyond pain, to inform treatment decisions for men with mCRPC.

Introduction: Cabazitaxel is one of several treatment options available for patients with metastatic castration-resistant prostate cancer who have progressed on docetaxel. Little is known about clinical factors that influence prognosis or treatment response for patients receiving cabazitaxel. Identifying prognostic and predictive factors could contribute to the optimal selection of patients for treatment after docetaxel.Methods: A retrospective review of patients enrolled on the cabazitaxel Canadian Early Access Program (C-EAP) was performed. Clinical factors were analyzed by univariable and multivariable Cox proportional hazards and logistic regression analysis to identify independent predictors of prognosis and response.Results: Forty-five patients from five centres in Canada were included in this study. On multivariable analysis, lower hemoglobin was associated with shorter survival. No other factors were independently associated with survival, prostate-specific antigen (PSA) response, or primary PSA progression.Conclusions: Clinical factors predicting survival or treatment response were not identified for men with castration-resistant prostate cancer receiving cabazitaxel. Larger studies may be necessary to identify clinical factors and biomarkers that identify whether patients should or should not receive cabazitaxel.

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Introduction: Our aim was to assess adherence to National Comprehensive Cancer Network (NCCN) and American Urological Association (AUA) guidelines for pelvic lymph node dissection (PLND) at the time of either robot-assisted (RARP) or open radical prostatectomy (ORP).Methods: We relied on the Surveillance, Epidemiology, and End Results-Medicare linked database and focused on localized prostate cancer (PCa) patients who were treated with either RARP or ORP between October 2008 and December 2009. Categorical and multivariable logistic regression analyses targeted two endpoints: 1) probability of guideline-recommended PLND; and 2) probability of no PLND, when not guideline-recommended.Results: Among 5268 PCa patients, adherence to NCCN PLND guideline was 56.9% during RARP and 76.5% during ORP (odds ratio [OR] 0.4, 95% confidence interval [CI] 0.3‒0.6). AUA PLND guideline adherence was 68.1% during RARP and 82.4% during ORP (OR 0.7, 95% CI 0.5‒0.9). When PLND was not recommended, it was more frequently performed during ORP according to either NCCN (OR 3.7, 95% CI 3.5‒3.9) or AUA (OR 2.7, 95% CI 2.6‒2.8). According to the NCCN guideline, at recommended PLND in ORP patients, 6.3% harboured lymph node invasion (LNI) (number needed to treat [NNT] 16) vs. 3.2% at RARP (NNT 31). According to the AUA guideline, at recommended PLND in ORP patients, 12.3% harboured LNI (NNT 8) vs. 5.1% RARP (NNT 19).Conclusions: Adherence to NCCN and AUA PLND guidelines was lower during RARP than during ORP when PLND was recommended. The rate of non-recommended PLND was also higher during ORP than during RARP. Technical considerations may be at play.

Introduction: In the TROPIC study, cabazitaxel improved overall survival in abiraterone-naïve metastatic castration-resistant prostate cancer (mCRPC) patients post-docetaxel. To evaluate cabazitaxel in routine clinical practice, an international, single-arm trial was conducted. Efficacy, safety, and quality of life (QoL) data were collected from Canadian patients enrolled. Overall survival and progression-free survival were not collected as part of this study. Importantly, prior abiraterone use was obtained and its impact on clinical parameters was examined.Methods: Sixty-one patients from nine Canadian centres were enrolled, with prior abiraterone use known for 60 patients. Prostatespecific antigen (PSA) response rate, safety, and impact on QoL life were analyzed as a function of prior abiraterone use.Results: Overall, 92% of patients were ECOG 0/1, 88% had bone metastases, and 25% visceral metastases. Patients treated without prior abiraterone (NoPriorAbi) (n=35, 58%) and with prior abiraterone (PriorAbi) (n=25, 42%) had similar baseline characteristics, except for age and prior cumulative docetaxel dose. Median number of cabazitaxel cycles received was similar between groups (NoPriorAbi=6, PriorAbi=7), as was PSA response rate (NoPriorAbi=36.4%, PriorAbi=45.0%, p=0.54). Almost one-third (31%) of patients received prophylactic granulocyte colony-stimulating factors. Most frequent Grade 3/4 toxicities were neutropenia (14.8%); anemia, febrile neutropenia, fatigue (each at 9.8%); and diarrhea (8.2%). No treatment-related adverse event leading to death was observed. QoL and pain were improved with no difference seen between groups. Treatment discontinuation was mainly due to disease progression (45.9%) and adverse events (32.8%).Conclusions: In routine clinical practice, cabazitaxel’s risk-benefit ratio in mCRPC patients previously treated with docetaxel seems to be maintained independent of prior abiraterone use.

Introduction: In men with bothersome lower urinary tract symptoms (LUTS), medical treatment usually represents the first line. We examined the patterns of medical management of benign prostatic hyperplasia (BPH) in the Montreal metropolitan area, within the context of a case control study focusing on incident prostate cancer.Methods: Cases were 1933 men with incident prostate cancer. Population controls included 1994 age-matched men. In-person interviews collected sociodemographic characteristics and medical history, including BPH diagnosis, its duration, and type of medical treatment received. Baseline characteristics were compared by the chi-square likelihood test for categorical variables and by the students t-test for continuously coded variables.Results: Overall, 1120 participants had history of BPH, of those 53.7% received medical treatment for BPH. Individuals with medically treated BPH, compared to individuals with medically untreated BPH, were older at index date [mean: 66.9 vs. 64.9 years, p˂0.001] and at diagnosis of BPH [mean: 62.3 vs. 60.3 years, p˂0.001]. They also had a longer duration of BPH-history [mean: 4.7 vs. 4.0 years, p=0.02]. Regarding medical treatment, monotherapy was more often used than combination therapy [87.6% vs. 12.4%, p˂0.001]. Alpha-blockers (69.9%) were most commonly used as monotherapy, followed by 5alpha-reductase inhibitors (5ARIs) (26.6%). Alpha-blockers plus 5ARIs were the most common combination therapy (97.3%).Conclusions: Despite evidence from randomized, controlled trials for better efficacy with use of combination therapy, monotherapy consisting of alpha-blockers or 5ARI, in that order, is most frequently used. Additionally, 5ARI use was more common than previously reported (27% vs. 15%).

Introduction: We assessed the incidence of contralateral prostate cancer (cPCa), contralateral EPE (cEPE) and contralateral positive surgical margins (cPSM) in patients diagnosed preoperatively with unilateral prostate cancer and evaluated risk factors predictive of contralateral disease extension.Methods: The occurrence of cPCa, cEPE and cPSM and the sidespecific nerve-sparing technique performed were collected postoperatively from 327 men diagnosed with unilateral prostate cancer at biopsy. Parameters, such as the localization, proportion, and percentage of cancer in positive cores, were prospectively collected.Results: Overall, 50.5% of patients had bilateral disease, and were at higher risk when associated with a positive biopsy core at the apex (p = 0.016). The overall incidence of ipsilateral EPE and cEPE were 21.4% and 3.4%, respectively (p < 0.001). Compared to cPCa, ipsilateral disease was at an almost 4-fold higher risk of extending out of the prostate (p < 0.001). None of the criteria tested were identified as useful predictors for cEPE. The low incidence of cEPE in our cohort could limit our ability to detect significance. The overall incidence of ipsilateral PSM and cPSM were 15.3% and 5.8%, respectively (p < 0.001). More aggressive nerve-sparing was not associated with a higher incidence of PSM. Prostate sides selected for more aggressive nerve-sparing were associated with younger patients (p < 0.001), a smaller prostate (p = 0.006), and a lower percentage of cancer in biopsy material (p = 0.008).Conclusion: Although the risk of cPCa is high in patients diagnosed with unilateral prostate cancer at biopsy, the risk of cEPE and cPSM is low, yet not insignificant. Contralateral aggressive nervesparing should be used with caution and should not compromise oncological outcome.

Introduction: We delineated Canadian regional differences in practice patterns in the management of upper tract urothelial carcinoma (UTUC) after nephroureterectomy and relate these to patient outcomes.Methods: A database was created with 1029 patients undergoing radical nephroureterectomy for UTUC between 1994 and 2009 at 10 Canadian centres. Demographic, clinical and pathological variables were collected from chart review. Practice pattern variables were defined as: open versus laparoscopic nephroureterectomy, management strategy for the distal ureter, performance of lymphadenectomy and administration of chemotherapy and/or radiation therapy. The outcome measures were overall (OS), disease-specific (DSS) and recurrence-free survival (RFS). The centres were divided into three regions (West, Central, East). Cox proportional multivariable linear regression analysis was used to determine the association between regional differences in practice patterns and clinical outcomes.Results: There was a significant difference in practice patterns between regions within Canada for: time from diagnosis to surgery (p = 0.001), type of surgery (open vs. laparoscopic, p < 0.01) and method of management of the distal ureter (p = 0.001). As well, there were significant differences in survival between regions across Canada: 5-year OS (West 70%, Central 81% and East 62%, p < 0.0001) and DSS (West=79%, Central=85%, East=75%, p = 0.007) were significantly different, but there was no difference in RFS (West 47%, Central 48%, East 46%, p = 0.88). Multivariable linear regression analysis demonstrated that the differences in survival were independent of region OS (p = 0.78), DSS (p = 0.30) or RFS (p = 0.43).Conclusion: There is significant disparity in practice patterns between regions within Canada, but these do not appear to have an effect on survival. We believe that the variability in practice is a reflection of the lack of standardized treatments for UTUC and underlines the need for multi-institutional studies in this disease.

Benign prostatic hyperplasia (BPH), and its clinical manifestation as lower urinary tract symptoms (LUTS), is a major health concern for aging men. There have been significant advances in the diagnosis and treatment of BPH in recent years. There has been a renewed interest in medical therapies and less invasive surgical techniques. As a consequence, the treatment needs of men with mild to moderate LUTS without evidence of prostate cancer can now be accomplished in a primary care setting. There are differences in the way urologists and primary care physicians approach the evaluation and management of LUTS due to BPH, which is not reflected in Canadian Urological Association (CUA) and American Urological Association (AUA) guidelines. A “shared care” approach involving urologists and primary care physicians represents a reasonable and viable model for the care of men suffering from LUTS. The essence of the model centres around educating and communicating effectively with the patient on BPH. This article provides primary care physicians with an overview of the diagnostic and management strategies outlined in recent CUA and AUA guidelines so that they may be better positioned to effectively deal with this patient population. It is now apparent that we must move away from the urologist as the first-line physician, and allow primary care physicians to accept a new role in the diagnosis and management of BPH.

Objectives: Two large, recently published, definitive trials evaluated the benefitsof 5-alpha reductase inhibitors (5ARIs). The Prostate Cancer Prevention Trial(PCPT) tested the effect of finasteride for prostate cancer prevention and the Medical Therapy of Prostatic Symptoms (MTOPS) tested its effect in benign prostatic hyperplasia(BPH). Both trials were strongly positive. However, the role of 5ARIs inthe clinical management of patients remains controversial. The consensus conference,which forms the basis for this report, attempted to develop an expertopinion, based on these studies, as to the optimal use of 5ARIs in patient management.Methods: The Canadian Consensus Meeting, organized by the Canadian Urology Research Consortium and the Canadian Urologic Oncology Group, held inToronto on May 7, 2006, focused on the new data from the PCPT and the MTOPS study. Internationally recognized experts and clinicians discussedthe implications of these data on clinical practice and issued a recommendationon the optimal management of patients with BPH.Results: The Consensus meeting agreed on the following recommendations:1. The overall results from the PCPT and MTOPS studies are of importanceto the urologic, as well as to the greater medical, community.2. Prostate management guidelines should be updated to include the resultsfrom both the MTOPS and the PCPT studies.3. In the PCPT, the incidence of high-grade cancer was higher in the finasteridetreatedgroup (6.4%), compared with the placebo group (5.1%). Subsequentanalyses strongly suggest that this increased prevalence was owing to a detectionbias caused by the reduction in prostate volume in patients takingfinasteride, compared with patients taking placebo. This resulted in animproved detection at biopsy of high-grade cancer in the finasteride group.4. In men who have large prostates and lower urinary tract symptoms (LUTS),5ARIs should be considered, both for the treatment of BPH and for prostatecancer risk reduction.5. For men who are concerned about prostate cancer, it is appropriate to discusschemoprevention with finasteride.6. Urologists are encouraged to disseminate these recommendations amongother healthcare professionals.