Improved Outcomes with Enzalutamide in Biochemically Recurrent Prostate Cancer.

BACKGROUND: Patients with prostate cancer who have high-risk biochemical recurrence have an increased risk of progression. The efficacy and safety of enzalutamide plus androgen-deprivation therapy and enzalutamide monotherapy, as compared with androgen-deprivation therapy alone, are unknown. METHODS: In this phase 3 trial, we enrolled patients with prostate cancer who had high-risk biochemical recurrence with a prostate-specific antigen doubling time of 9 months or less. Patients were randomly assigned, in a 1:1:1 ratio, to receive enzalutamide (160 mg) daily plus leuprolide every 12 weeks (combination group), placebo plus leuprolide (leuprolide-alone group), or enzalutamide monotherapy (monotherapy group). The primary end point was metastasis-free survival, as assessed by blinded independent central review, in the combination group as compared with the leuprolide-alone group. A key secondary end point was metastasis-free survival in the monotherapy group as compared with the leuprolide-alone group. Other secondary end points were patient-reported outcomes and safety. RESULTS: A total of 1068 patients underwent randomization: 355 were assigned to the combination group, 358 to the leuprolide-alone group, and 355 to the monotherapy group. The patients were followed for a median of 60.7 months. At 5 years, metastasis-free survival was 87.3% (95% confidence interval [CI], 83.0 to 90.6) in the combination group, 71.4% (95% CI, 65.7 to 76.3) in the leuprolide-alone group, and 80.0% (95% CI, 75.0 to 84.1) in the monotherapy group. With respect to metastasis-free survival, enzalutamide plus leuprolide was superior to leuprolide alone (hazard ratio for metastasis or death, 0.42; 95% CI, 0.30 to 0.61; P<0.001); enzalutamide monotherapy was also superior to leuprolide alone (hazard ratio for metastasis or death, 0.63; 95% CI, 0.46 to 0.87; P = 0.005). No new safety signals were observed, with no substantial between-group differences in quality-of-life measures. CONCLUSIONS: In patients with prostate cancer with high-risk biochemical recurrence, enzalutamide plus leuprolide was superior to leuprolide alone with respect to metastasis-free survival; enzalutamide monotherapy was also superior to leuprolide alone. The safety profile of enzalutamide was consistent with that shown in previous clinical studies, with no apparent detrimental effect on quality of life. (Funded by Pfizer and Astellas Pharma; EMBARK ClinicalTrials.gov number, NCT02319837.).

Side effect management algorithms for niraparib/abiraterone acetate in prostate cancer.

INTRODUCTION: Niraparib, a PARP1/2 inhibitor, is newly approved in combination with abiraterone acetate (AA) plus prednisone or prednisolone (niraparib/AA+P) for the treatment of adult patients with BRCA-mutated, treatment-naïve metastatic castration resistant prostate cancer (mCRPC). Detailed guidance beyond the prescribing information may be helpful in managing the side effect profile and dosing practicalities of this combination therapy. MATERIALS AND METHODS: A panel of specialists convened to design management algorithms for four common niraparib/AA+P treatment-related adverse events (AEs) in mCRPC; anemia, thrombocytopenia, hypertension, and nausea. The algorithms build on Health Canada-approved prescribing information to highlight practical considerations related to monitoring, treatment adjustment, and specialist referral to support clinical practice. RESULTS: The panel's recommendations were largely aligned with the niraparib/AA+P product monograph. Single agent AA+P followed by reintroduction niraparib/AA+P using the low dose formulation of niraparib/AA were common strategies for managing higher grade AE's. Recommendations for hypertension management were expanded to include a sequence of anti-hypertensive medication trials prior to a change in anti-cancer therapy, where feasible. CONCLUSION: These algorithms are intended to provide practical assistance to Canadian clinicians managing the most common AEs encountered with the novel combination, niraparib/AA+P, for mCRPC.

Development and Implementation of a Continuing Medical Education Program in Canada: Knowledge Translation for Renal Cell Carcinoma (KT4RCC).

An in-person multidisciplinary continuing medical education (CME) program was designed to address previously identified knowledge gaps regarding quality indicators of care in kidney cancer. The objective of this study was to develop a CME program and determine if the program was effective for improving participant knowledge. CME programs for clinicians were delivered by local experts (uro-oncologist and medical oncologist) in four Canadian cities. Participants completed knowledge assessment tests pre-CME, immediately post-CME, and 3-month post-CME. Test questions were related to topics covered in the CME program including prognostic factors for advanced disease, surgery for advanced disease, indications for hereditary screening, systemic therapy, and management of small renal masses. Fifty-two participants attended the CME program and completed the pre- and immediate post-CME tests. Participants attended in Ottawa (14; 27%), Toronto (13; 25%), Québec City (18; 35%), and Montréal (7; 13%) and were staff urologists (21; 40%), staff medical oncologists (9; 17%), fellows (5; 10%), residents (16; 31%), and oncology nurses (1; 2%). The mean pre-CME test score was 61% and the mean post-CME test score was 70% (p = 0.003). Twenty-one participants (40%) completed the 3-month post-CME test. Of those that completed the post-test, scores remained 10% higher than the pre-test (p value 0.01). Variability in test scores was observed across sites and between French and English test versions. Urologists had the largest specialty-specific increase in knowledge at 13.8% (SD 24.2, p value 0.02). The kidney cancer CME program was moderately effective in improving provider knowledge regarding quality indicators of kidney cancer care. These findings support continued use of this CME program at other sites.

A survey of patient expectations regarding sexual function following radical prostatectomy.

OBJECTIVE: To assess the understanding of patients, who had previously undergone radical prostatectomy (RP), about their postoperative sexual function, as clinical experience suggests that some RP patients have unrealistic expectations about their long-term sexual function. PATIENTS AND METHODS: Patients presenting within 3 months of their open RP or robot-assisted laparoscopic prostatectomy (RALP) were questioned about the sexual function information that they had received preoperatively. Patients were questioned about erectile function (EF), postoperative ejaculatory status, orgasm, and postoperative penile morphology changes. Statistical analyses were performed to assess for differences between patients who underwent open RP vs RALP. RESULTS: In all, 336 consecutive patients (from nine surgeons) with a mean (SD) age of 64 (11) years had the survey instrument administered (216 underwent open RP and 120 underwent RALP). There were no significant differences in patient age or comorbidity profiles between the two groups. Only 38% of men had an accurate recollection of their nerve-sparing status. The mean (SD) elapsed time after RP at the time of postoperative assessment was 3 (2) months. RALP patients expected a shorter EF recovery time (6 vs 12 months, P = 0.02), a higher likelihood of recovery back to baseline EF (75% vs 50%, P = 0.01), and a lower potential need for intracavernosal injection therapy (4% vs 20%, P = 0.01). Almost half of all patients were unaware that they were rendered anejaculatory by their surgery. None of the RALP patients and only 10% of open RP patients recalled being informed of the potential for penile length loss (P < 0.01) and none were aware of the association between RP and Peyronie's disease. CONCLUSIONS: Patients who have undergone RP have largely unrealistic expectations about their postoperative sexual function.

Practice patterns and predictors of treatment intensification in patients with metastatic castration-sensitive prostate cancer.

INTRODUCTION: Treatment intensification beyond androgen deprivation therapy (ADT) has shown survival benefit in patients with metastatic castration-sensitive prostate cancer (mCSPC). There is a need to better understand how these novel treatments fit in real-world practice. METHODS: Using electronic medical records and administrative data, a population-based, retrospective cohort study of patients newly diagnosed with de novo mCSPC between 2010 and 2020 in Alberta, Canada, and initiated ADT was conducted. Treatment intensification was defined as the receipt of apalutamide, abiraterone acetate, enzalutamide, or chemotherapy (e.g., docetaxel) within 180 days of ADT initiation. RESULTS: A total of 2515 de novo mCSPC were identified, with 2098 (83%) patients initiating ADT post-diagnosis. Of those, 525 (25%) received intensification beyond ADT. The percentage of patients who were intensified was 3% in 2010-2013 and gradually increased to 67% in 2020. From 2014-2017, docetaxel was the most commonly used approach, although it was supplanted by abiraterone acetate, apalutamide and enzalutamide from 2018 onwards. In multivariable logistic regression analyses of patients diagnosed from 2014-2020, significant predictors of intensification were younger age at diagnosis, lower Charlson comorbidity index, greater number of metastatic sites, shorter time to ADT initiation, referral to a medical oncologist, transurethral resection of the prostate or radiation prior to ADT, and more recent year of diagnosis (all p<0.05). Intensification increased for patients living in rural areas and with higher disease burden in 2018+ compared to 2014-2017. CONCLUSIONS: There has been a considerable increase in the use of ADT intensification therapies that correspond with the timing of clinical trial data and approvals of novel agents.

Addressing controversial areas in the management of advanced prostate cancer in Canada Areas of consensus and controversy from the third Canadian consensus forum.

INTRODUCTION: The management of prostate cancer (PCa) is rapidly evolving. Treatment and diagnostic options grow annually, however, high-level evidence for the use of new therapeutics and diagnostics is lacking. In November 2022, the Genitourinary Research Consortium held its 3rd Canadian Consensus Forum (CCF3) to provide guidance on key controversial areas for management of PCa. METHODS: A steering committee of eight multidisciplinary physicians identified topics for discussion and adapted questions from the Advanced Prostate Cancer Consensus Conference 2022 for CCF3. Questions focused on management of metastatic castration-sensitive prostate cancer (mCSPC); use of novel imaging, germline testing, and genomic profiling; and areas of non-consensus from CCF2. Fifty-eight questions were voted on during a live forum, with threshold for "consensus agreement" set at 75%. RESULTS: The voting panel consisted of 26 physicians: 13 urologists/uro-oncologists, nine medical oncologists, and four radiation oncologists. Consensus was reached for 32 of 58 questions (one ad-hoc). Consensus was seen in the use of local treatment, to not use metastasis-directed therapy for low-volume mCSPC, and to use triplet therapy for synchronous high-volume mCSPC (low prostate-specific antigen). Consensus was also reached on sufficiency of conventional imaging to manage disease, use of germline testing and genomic profiling for metastatic disease, and poly (ADP-ribose) polymerase (PARP) inhibitors for BRCA-positive prostate cancer. CONCLUSIONS: CCF3 identified consensus agreement and provides guidance on >30 practice scenarios related to management of PCa and nine areas of controversy, which represent opportunities for research and education to improve patient care. Consensus initiatives provide valuable guidance on areas of controversy as clinicians await high-level evidence.

Real-world utilization and outcomes of docetaxel among older men with metastatic prostate cancer: a retrospective population-based cohort study in Canada.

BACKGROUND: The adoption of docetaxel for systemic treatment of metastatic prostate cancer (PCa), in both castration-sensitive (mCSPC) and castration-resistant (mCRPC) settings, is poorly understood. This study examined the real-world utilization of docetaxel in these patients and their outcomes. METHODS: A retrospective population-based study used administrative data from Ontario, Canada, to identify men aged ≥66 years who were diagnosed with de novo mCSPC or mCRPC between 2014 and 2019 and received docetaxel. The study assessed treatment tolerability and toxicity, and survival in both cohorts. Descriptive and comparative statistical analysis were conducted. RESULTS: The study identified 11.2% (399/3556) and 13.2% (203/1534) patients diagnosed with de novo mCSPC and with mCRPC who received docetaxel respectively. The median age in both cohorts was 72 years (IQR: 68-76). Overall, 43.9% (n = 175) patients with de novo mCSPC and 52.1% (n = 85) with mCRPC completed ≥6 cycles of docetaxel. Over two-fifth also needed dose adjustments in both cohorts. Hospitalization or emergency department visit for febrile neutropenia were noted in 15.8% (n = 63) of de novo mCSPC patients and similarly in 19% (n = 31) of mCRPC cohort. The median survival of PCa patients who completed ≥6 cycles of docetaxel was significantly longer relative to those who completed <4 cycles: 32.7 vs. 23.5 months (p < 0.001) for mCSPC and 20.5 vs. 10.7 (p = 0.012) for mCRPC respectively. CONCLUSIONS: In this population-based study of elderly patients with metastatic PCa, treatment with docetaxel was associated with poor tolerability and higher toxicity compared with clinical trials. Receipt of limited cycles and reduced overall dose of docetaxel were associated with inferior overall survival.

Genetic testing practices among specialist physicians who treat prostate cancer A Canadian, cross-sectional survey.

INTRODUCTION: In patients with prostate cancer (PCa), the identification of an alteration in genes associated with homologous recombination repair (HRR) has implications for prognostication, optimization of therapy, and familial risk mitigation. The aim of this study was to assess the genomic testing landscape of PCa in Canada and to recommend an approach to offering germline and tumor testing for HRR-associated genes. METHODS: The Canadian Genitourinary Research Consortium (GURC) administered a cross-sectional survey to a largely academic, multidisciplinary group of investigators across 22 GURC sites between January and June 2022. RESULTS: Thirty-eight investigators from all 22 sites responded to the survey. Germline genetic testing was initiated by 34%, while 45% required a referral to a genetic specialist. Most investigators (82%) reported that both germline and tumor testing were needed, with 92% currently offering germline and 72% offering tissue testing to patients with advanced PCa. The most cited reasons for not offering testing were an access gap (50%), uncertainties around who to test and which genes to test, (33%) and interpreting results (17%). A majority reported that patients with advanced PCa (74-80%) should be tested, with few investigators testing patients with localized disease except when there is a family history of PCa (45-55%). CONCLUSIONS: Canadian physicians with academic subspecialist backgrounds in genitourinary malignancies recognize the benefits of both germline and somatic testing in PCa; however, there are challenges in accessing testing across practices and specialties. An algorithm to reduce uncertainty for providers when ordering genetic testing for patients with PCa is proposed.

Patterns of care for non-metastatic castration-resistant prostate cancer: A population-based study.

Objectives: To describe patterns of practice of PSA testing and imaging for Ontario men receiving continuous ADT for the treatment of non-metastatic castration-resistant prostate cancer (nmCRPC). Patients and Methods: This was a retrospective, longitudinal, population-based study of administrative health data from 2008 to 2019. Men 65 years and older receiving continuous androgen deprivation therapy (ADT) with documented CRPC were included. An administrative proxy definition was applied to capture patients with nmCRPC and excluded those with metastatic disease. Patients were indexed upon progression to CRPC and were followed until death or end of study period to assess frequency of monitoring with PSA tests and conventional imaging. A 2-year look-back window was used to assess patterns of care leading up to CRPC as well as baseline covariates. Results: At a median follow-up of 40.1 months, 944 patients with nmCRPC were identified. Their median time from initiation of continuous ADT to CRPC was 26.0 months. 60.7% of patients had their PSA measured twice or fewer in the year prior to index, and 70.7% patients did not receive any imaging in the year following progression to CRPC. Throughout the study period, 921/944 (97.6%) patients with CRPC progressed to high-risk (HR-CRPC) with PSA doubling time ≤ 10 months, of which more than half received fewer than three PSA tests in the year prior to developing HR-CRPC, and 30.9% received no imaging in the subsequent year. Conclusion: PSA testing and imaging studies are underutilized in a real-world setting for the management of nmCRPC, including those at high risk of developing metastatic disease. Infrequent monitoring impedes proper risk stratification, disease staging and detection of treatment failure and/or metastases, thereby delaying the necessary treatment intensification with life-prolonging therapies. Adherence to guideline recommendations and the importance of timely staging should be reinforced to optimize patient outcomes.

Real-world use of systemic therapies in men with metastatic castration resistant prostate cancer (mCRPC) in Canada.

BACKGROUND: Management of advanced prostate cancer has evolved rapidly with the availability of multiple systemic treatments such as androgen-receptor axis-targeted therapies (ARATs), taxane-based chemotherapy, radium-223, and other approaches. However, limited data exists on real-world treatment selection and clinical outcomes. This study examines the utilization and survival impact of these therapies in men with metastatic castration-resistant prostate cancer (mCRPC) in the real-world setting of Ontario, Canada. METHODS: This study was a retrospective, longitudinal, population-based study of administrative claims data between January 2016 and April 2020. Men ≥ 66 years with mCRPC receiving advanced treatment were included. Patients were indexed on the day they initiated mCRPC treatment and followed up until death or end of study period to assess treatment and survival. Multinomial regression was used to model the association between baseline covariates, treatment and survival. RESULTS: Median age was 75 years among the 944 mCRPC patients who received life-prolonging therapies during this time period. Over 90% of patients used an ARAT as a first-line therapy, and 71.5% received only first-line therapy before death or censoring. Of patients that received two or more lines, over 80% received subsequent therapy with a different mechanism of action. Median overall survival was 18.9 months. CONCLUSIONS: ARATs have become the predominant first-line systemic treatment option for mCRPC patients in recent years. Notably, the majority of patients received only a single line of life-prolonging therapy after developing mCRPC. In keeping with the recognized efficacy-effectiveness gap, real-world outcomes in this cohort appear poorer than in clinical trials.

Age, obesity, medical comorbidities and surgical technique are predictive of symptomatic anastomotic strictures after contemporary radical prostatectomy.

PURPOSE: Anastomotic strictures are relatively common after radical prostatectomy and are associated with significant morbidity, often requiring multiple surgical interventions. There is controversy in the literature regarding which factors predict the development of anastomotic strictures. In this study we determined predictors of symptomatic anastomotic strictures following contemporary radical prostatectomy. MATERIALS AND METHODS: Between 1999 and 2007, 4,592 consecutive patients underwent radical prostatectomy without prior radiotherapy at our institution. Data were collected from prospective surgical and institutional morbidity databases, and retrospectively from inpatient and outpatient medical and billing records. Cases were assigned a Charlson score to account for comorbidities. Complications were graded according to the modified Clavien classification. RESULTS: Open radical prostatectomy was performed in 3,458 men (75%) and laparoscopic radical prostatectomy was performed in 1,134 (25%). The laparoscopic radical prostatectomy group included 97 robotic-assisted cases. Median patient age was 59.5 years (IQR 54.7, 64.2). Symptomatic anastomotic strictures developed in 198 patients (4%) after a median postoperative followup of 3.5 months (IQR 2.1, 6.1). On multivariate analysis significant predictors included patient age, body mass index, Charlson score, renal insufficiency, individual surgeon, surgical approach and the presence of postoperative urine leak or hematoma. CONCLUSIONS: Patient factors as well as technical factors influence the development of symptomatic anastomotic strictures following contemporary radical prostatectomy. The impact of these factors is influenced by the individual surgeon and the approach used.

Predictors of symptomatic lymphocele after radical prostatectomy and bilateral pelvic lymph node dissection.

OBJECTIVES: Lymphocele is the most common complication of pelvic lymphadenectomy (PLND). We sought to determine predictors of symptomatic lymphocele after radical prostatectomy (RP) and PLND, and in particular, to determine if the number of drains placed represents an independent predictor. METHODS: Between January 1999 and June 2007, 4173 consecutive patients underwent bilateral PLND at the time of either open or laparoscopic RP. Lymphoceles were identified in patients undergoing imaging as a result of symptoms suspicious for lymphocele, such as fever, abdominal pain or lower extremity swelling. Routine postoperative imaging was not carried out. Cox proportional hazards analysis was carried out using forced variable entry to obtain maximum likelihood estimates of the hazard ratios and 95% confidence intervals using the number of drains placed, number of nodes removed, RP approach and use of prophylactic low-molecular-weight heparin (LMWH) as predictors of symptomatic lymphocele. RESULTS: There were 164 patients (4%) with a symptomatic lymphocele on follow up, with a median time to presentation of 19 days. The primary presenting complaints were fever in 47%, abdominal pain in 40%, lower extremity swelling in 37%, genital swelling in 25%, groin pain in 22%, abdominal swelling in 9%, and back and flank pain in 6% and 5%, respectively. Median lymphocele diameter was 5 cm. Significant predictors of symptomatic lymphocele on multivariate analysis included number of nodes removed and use of LMWH, but not number of drains placed. CONCLUSIONS: Use of prophylactic LMWH and a higher node count are predictive of a higher incidence of symptomatic lymphocele after RP and PLND.

Real-World Use of Androgen-Deprivation Therapy: Intensification Among Older Canadian Men With de Novo Metastatic Prostate Cancer.

Background: Despite the wealth of evidence demonstrating the efficacy of treatment intensification beyond androgen-deprivation therapy (ADT) among patients with de novo metastatic castration-sensitive prostate cancer (mCSPC), little is known of its real-world use. This study examined the real-world uptake of ADT treatment intensification among older men in a large Canadian province. Methods: We performed a retrospective population-based cohort study using province-wide linked administrative data in Ontario, Canada. Patients 66 years of age and older with de novo mCSPC were included and their treatment with conventional ADT-based regimens, ADT plus next-generation androgen receptor axis-targeted therapy, and ADT plus docetaxel were identified and stratified by time. Results: From 2014 to 2019, 3556 patients were identified with de novo mCSPC. Most patients (n = 2794 [78.6%]) were treated with a conventional ADT regimen, whereas 399 (11.2%) patients received ADT intensification with docetaxel and 52 (1.5%) patients received abiraterone acetate plus prednisone. In a time-stratified analysis of ADT intensification before and after the pivotal AA+P trial (LATITUDE), AA+P uptake increased from 0.5% to 3.0%, whereas docetaxel use dropped from 12.0% to 10.0%. The median survival of the study population was 18 months (interquartile range = 10-31). Conclusions: The majority of patients with de novo mCSPC are treated with ADT alone in the Canadian real-world setting, despite randomized clinical trial evidence of benefit with the use of ADT-intensified regimens. As ADT treatment intensification is substantially underused, better understanding of the barriers to treatment and targeted education to address them are needed.

Prognostic Association between Common Laboratory Tests and Overall Survival in Elderly Men with De Novo Metastatic Castration Sensitive Prostate Cancer: A Population-Based Study in Canada.

De novo cases of metastatic prostate cancer (mCSPC) are associated with poorer prognosis. To assist in clinical decision-making, we aimed to determine the prognostic utility of commonly available laboratory-based markers with overall survival (OS). In a retrospective population-based study, a cohort of 3556 men aged ≥66 years diagnosed with de novo mCSPC between 2014 and 2019 was identified in Ontario (Canada) administrative database. OS was assessed by using the Kaplan-Meier method. Multivariate Cox regression analysis was performed to evaluate the association between laboratory markers and OS adjusting for patient and disease characteristics. Laboratory markers that were assessed include neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), albumin, hemoglobin, serum testosterone and PSA kinetics. Among the 3556 older men with de novo mCSPC, their median age was 77 years (IQR: 71-83). The median survival was 18 months (IQR: 10-31). In multivariate analysis, a statistically significant association with OS was observed with all the markers (NLR, PLR, albumin, hemoglobin, PSA decrease, reaching PSA nadir and a 50% PSA decline), except for testosterone levels. Our findings support the use of markers of systemic inflammation (NLR, PLR and albumin), hemoglobin and PSA metrics as prognostic indicators for OS in de novo mCSPC.

Results from a Canadian consensus forum of key controversial areas in the management of advanced prostate cancer: Recommendations for Canadian healthcare providers.

INTRODUCTION: Rapid progress in diagnostics and therapeutics for the management of prostate cancer (PCa) has 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 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 predetermined 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.

Impact of prior prostate radiation on complications after radical prostatectomy.

PURPOSE: Salvage radical prostatectomy is associated with a higher complication rate than radical prostatectomy without prior radiotherapy but the magnitude of the increase is not well delineated. MATERIALS AND METHODS: A total of 3,458 consecutive patients underwent open radical prostatectomy and 98 underwent open salvage radical prostatectomy from January 1999 to June 2007. Data were collected from prospective surgical and institutional morbidity databases, and retrospectively from billing records and medical records. Medical and surgical complications were captured, graded by the modified Clavien classification and classified by time of onset. RESULTS: Median followup after salvage radical prostatectomy and radical prostatectomy was 34.5 and 45.5 months, respectively. Patients with salvage had significantly higher median age, modified Charlson comorbidity score, clinical and pathological stage, and Gleason score. They were less likely to have organ confined disease and more likely to have seminal vesicle invasion and nodal metastasis. There was no significant difference in median operative time, blood loss or transfusion rate. The salvage group had a higher adjusted probability of medical and surgical complications, including urinary tract infection, bladder neck contracture, urinary retention, urinary fistula, abscess and rectal injury. Only 1 of 4 potent patients with salvage prostatectomy who underwent bilateral nerve sparing recovered erection adequate for intercourse. The 3-year actuarial recovery of continence was 30% (95% CI 19-41). CONCLUSIONS: Medical and surgical complications of prostatectomy are significantly increased in the setting of prior radiotherapy. Understanding the magnitude of this increased risk is important for patient counseling.

Temporal Trends in Selecting Patients for Partial Nephrectomy for Small Renal Cell Carcinomas in Alberta, Canada.

BACKGROUND: When technically feasible, partial nephrectomy (pN) is preferred over radical nephrectomy (rN) due to similar oncological control with preservation of renal function. Here, we evaluate the incorporation of pN into practice for small renal masses and examine the associated outcomes. METHODS: We included patients who had undergone either a partial or radical nephrectomy in Alberta, Canada for renal cell carcinomas with pathology tumor stage T1a between 2002 and 2014 (N=1449). Patients were excluded if they had multiple tumors or if they were on dialysis prior to nephrectomy. RESULTS: pN use increased over the duration of the study period. Patients treated after the introduction of guidelines (2007) recommending the use of pN were significantly more likely to receive a pN (OR: 2.709, 95% CI: 1.944-3.775; p<0.001) after adjusting for baseline estimated glomerular filtration rate (GFR), age, and sex. Patients who received rN were at significantly increased risk of death (HR: 1.528, 95% CI: 1.029-2.270; p=0.036) after controlling for baseline GFR, age, and sex. Baseline GFR significantly affected odds of receiving pN (p<0.050) in the entire cohort, but subgroup analysis of more recently diagnosed patients (2011-2014) showed that only patients with kidney failure (GFR <15) were less likely to have received pN. DISCUSSION: The utilization of pN for patients with pT1a renal cell carcinoma has increased significantly over time and has been accelerated by the introduction of guideline recommendations. Patients treated with pN over the study period had superior overall survival.

Changes in risk-group stratification of patients undergoing radical prostatectomy at the Southern Alberta Institute of Urology over time.

INTRODUCTION: Prostate cancer is the most common cancer among men, but overall mortality rates remain low, due to the preponderance of low-risk disease. Over the last decade, there has been a shift toward more conservative management in low-risk prostate cancer, in order to minimize unnecessary intervention. This study aimed to evaluate the number of low-risk radical prostatectomies (RPs) being performed at the Southern Alberta Institute of Urology over a 10-year period. METHODS: We retrospectively reviewed all patients who underwent RP from 2005 to 2014 at our institution. Patients were stratified by D'Amico risk classification and grade group based on 12-core transrectal ultrasound-guided biopsy (TRUS-bx) results. RP findings are reported from February 2005 to October 2014 to describe concordance between TRUS-bx and RPs. Basic descriptive analyses were used for this study. RESULTS: Over the study period, 2,310 RPs were performed in our institution. Overall, 35.2% of these were performed on men with low-risk prostate cancer. From 2005 to 2014, the proportion of RPs performed for low-risk prostate cancer dropped from 54.0% to 8.9%, and 49.8% of patients who underwent RP for low-risk disease experienced pathologic upgrading, though only 3.8% were upgraded to grade group 3 or greater. Other adverse pathological findings were uniformly low among the low-risk group. CONCLUSION: The proportion of patients undergoing RP at our center for low-risk prostate cancer decreased significantly over the 10 years evaluated in this study, reflecting current global trends toward active surveillance in the management of low-risk prostate cancer.

Low compliance with guidelines for re-staging in high-grade T1 bladder cancer and the potential impact on patient outcomes in the province of Alberta.

INTRODUCTION: Despite high-level evidence of benefit, early repeat resection (ERR) among high-grade T1 bladder cancer (HGT1-BC) patients remains low in several non-Canadian jurisdictions and rates in Canada are largely unreported. We evaluated rates of ERR and trends over time in Alberta. We also examined factors associated with uptake of ERR. METHODS: We conducted a retrospective review of data from all patients diagnosed with HGT1-BC from 2007 through 2011. Patients were identified from the Alberta Cancer Registry. Patients with a non-urothelial carcinoma of the bladder and those with invasion into the prostate or metastatic disease were excluded. We collected demographic and clinicopathologic information from patients' electronic medical records. RESULTS: A total of 600 patients diagnosed with HGT1-BC were included. Overall, 167 patients (27.8%) received an ERR; however, the rate increased in a non-linear fashion from 27.4% in 2007 to 37.8% in 2011. Factors associated with ERR included age <80 years (p=0.021) and centre at which the initial transurethral resection of bladder tumour (TURBT) was performed (p=0.013). Median overall survival (OS) was not reached, but five-year OS was 72.7% (95% CI 68.9, 76.5) for those who received an ERR and 55.3% (95% CI 52.5, 58.1) for those who did not. CONCLUSIONS: Use of ERR in patients with HGT1-BC is improving over time. Regional variation in practice suggests the need for implementation strategies (i.e., provincial clinical care pathways) to standardize practice and set indicators for future measurement and reporting. Targeted interventions would require further investigation around the reasons for variation in practice.

Predictors of referral for neoadjuvant chemotherapy prior to radical cystectomy for muscle-invasive bladder cancer and changes in practice over time.

INTRODUCTION: In patients with non-metastatic muscle-invasive bladder cancer (MIBC) fit for curative therapy, a multidisciplinary approach consisting is recommended. This approach includes local treatment (usually radical cystectomy), ideally combined with neoadjuvant chemotherapy (NACT). Despite a survival benefit with NACT, uptake remains low. We assessed NACT consultation in Alberta and examined associative factors, as well as the relationship to survival. METHODS: Patients with MIBC were identified through the Alberta Cancer Registry. Demographic and clinicopathologic information was collected from electronic medical records between 2007 and 2011. In addition to descriptive statistics, logistic regression was used to determine factors associated with receiving NACT consultation. Overall survival was described using a Kaplan-Meier estimate. RESULTS: Of the 315 radical cystectomy patients, 140 (45.1%, 95% confidence interval [CI] 39.5, 50.8) received NACT consultation. Patients ≥80 years (odds ratio [OR] 0.21, 95% CI 0.08, 0.57, p = 0.002) and those treated in Calgary (OR 0.11, 95% CI 0.05, 0.25, p < 0.001) were less likely to receive NACT consultation. The rate of NACT consultation increased steadily from 2007 to 2011 (OR 1.23, 95% CI 1.04, 1.45 per year of diagnosis, p = 0.018). After a median follow-up of 28.1 months (range: 14.6-50.3), median survival was 54.7 months for patients who received NACT consultation versus 31.2 months for those who did not (p = 0.030). CONCLUSIONS: NACT consultation in patients with MIBC undergoing radical cystectomy has improved over time; however, regional differences underscore the need for a standardized approach to NACT consultation, including common referral mechanisms.