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PURPOSE: Several new drug therapies have been approved in CRPC in the past decade. However, little is known about their potential overuse at the end of life. Cancer therapy use at the end of life has been considered an indicator of overtreatment. The study objective was to describe CRPC drug use in the last month of life of CRPC patients in Quebec. PATIENTS AND METHODS: Using administrative databases from the province of Quebec in Canada, we identified patients who received medical or surgical castration treatment, received one or more CRPC drugs (chemotherapy, abiraterone, or bone-targeted therapy), and died between 2001 and 2013. CRPC drug use in the last month of life was the primary outcome. RESULTS: The cohort consisted of 1,148 patients with CRPC. A total of 316 men (27.5%) received a CRPC drug in the last month of life. For those who received chemotherapy, abiraterone, and bone-targeted therapy, 10.2%, 27.8%, and 31.8% received them in the last month of life, respectively. In multivariable analyses, age older than 75 years (odds ratio [OR], 0.75; 95% CI, 0.57 to 0.99), and prostate cancer diagnosis received less than 24 months earlier (OR, 0.43; 95% CI, 0.26 to 0.72) were associated with less CRPC drug use. Relative to dying between 2005 and 2011, dying between 2012 and 2013 (OR 1.60; 95% CI, 1.18 to 2.18) was associated with greater CRPC drug use. CONCLUSION: More than one quarter of patients received CRPC drug therapies in the last month of life. Persistent chemotherapy, abiraterone, bone-targeted therapies, and medical castration drugs in the last month of life may be an indicator of inappropriate and expensive end-of-life care.

62 Background: Novel hormonal agents (NHAs) such abiraterone (ABI) and enzalutamide (ENZA) have demonstrated similar survival benefits against placebo groups in their respective clinical trials leading to their regulatory approval in both the pre- and post-chemotherapy settings in metastatic castration-resistant prostate cancer (mCRPC). Despite the overall tolerable risk profile, certain signals of cardiovascular toxicity were reported for these agents in clinical trials but little is known about their incidence in clinical practice. The objective was to assess the comparative cardiovascular safety of ABI and ENZA in patients with mCRPC in the real-world. Methods: A retrospective population-based cohort was extracted from Quebec public healthcare administrative databases. Patients were selected on the basis of having received androgen deprivation therapy prior to initiating a novel hormonal agent (ABI or ENZA) between 2012 and 2016. The primary outcome of interest was cardiovascular-related hospitalization (composite outcome that included acute coronary disease, cerebrovascular disease, heart failure, arrhythmia and other cardiovascular causes). Inverse probability of treatment weighting (IPTW) with the propensity score was used to adjust for measured baseline confounders including pre-existing cardiovascular disease. Results: The cohort comprises 2,183 patients, with 1,773 (81.2%) in the ABI group and 410 (18.8%) in the ENZA group. Before IPTW, mean age of the ENZA group was higher than the ABI group (78 vs 76). There were more ENZA patients with pre-existing arrythmia (ABI: 10.7%, ENZA: 15.1%) and diabetes (ABI: 21.5%, ENZA: 25.1%). Crude incidence rates of cardiovascular-related hospitalization were of 10 events per 100 person-years (PYs) and of 7 events per 100 PYs for the ABI and ENZA groups, respectively. After applying IPTW, all baseline variables were well balanced across both groups with standardized differences < 0.05. The ABI group was at greater risk of cardiovascular-related hospitalization compared to the ENZA group (IPTW-hazard ratio (HR): 1.79, 95% confidence interval (95%CI): 1.04-3.09). The risk of hospitalization for heart failure was greater in ABI (IPTW-HR: 3.02, 95%CI: 1.17-7.78). Conclusions: In our study population, there was a greater risk of cardiovascular-related hospitalizations for ABI users relative to ENZA users, in particular for hospitalization for heart failure. Given the lack of evidence from randomized head-to-head comparisons of both agents, these results provide clinicians with additional insight on the cardiovascular risks of mCRPC patients treated with NHAs in the real-world and further large studies are required to corroborate these findings.

5530 Background: The accuracy of the extracellular vesicle-fingerprint score (EV-FPS) test to predict clinically significant prostate cancer (PCa; Gleason grade (GG) ≥ 3) from indolent disease (GG ≤ 2) and avoid unnecessary prostate biopsies was determined at the point of prostate biopsy decision. Methods: Clinical data, health information, and blood samples were collected from a prospective validation cohort of 415 men, without prior PCa diagnosis, referred to urology clinics for prostate biopsy or transurethral prostate surgery (June 2014-Dec 2016). The patient’s EV-FPS risk score was calculated by combining machine learning model-analyzed microflow cytometry data from EV biomarkers with logistic regression-analyzed patient-centric clinical features. The plasma-derived EV biomarkers were prostate-specific membrane antigen, polysialic acid and ghrelin-growth hormone receptor. The patient clinical features were; age, ethnicity, PCa family history, PSA levels, abnormal digital rectal examination (DRE) and prior negative prostate biopsy. Together, the biomarkers and clinical features provided specificity for clinically significant PCa. Results: The EV-FPS test identified clinically significant PCa patients with high accuracy (0.81 area under curve) at 95% sensitivity and 97% negative predictive value. Using a 7.85% probability cut-off after test validation; 95% of the patients with GG ≥ 3 would have been found before biopsy, 35% biopsies would have been avoided and diagnosis of GG ≥ 3 PCa would have been missed in only 5% of the cohort. Conclusions: This minimally invasive EV-FPS test accurately predicted clinically significant PCa in men with high EV-FPS risk scores, high PSA level and/or abnormal DRE. Therefore, men with low EV-FPS risk scores could potentially avoid unnecessary prostate biopsies. Clinical care cut-offs to calculate the number of biopsies that could have been avoided, and the percentage of GG ≥ 1 to GG ≥ 3 PCa that could have had a delayed diagnosis. [Table: see text]

40 Background: The approval of novel hormonal agents (NHAs), abiraterone and enzalutamide, have increased the therapeutic arsenal available in metastatic castration-resistant prostate cancer (mCRPC). However, the use of chemotherapy and other antineoplastics at the end of life has been suggested as an indicator of poor quality of care. In this study, we report the use of NHAs at the end of life in men with mCRPC in the province of Quebec, Canada. Methods: Using Quebec public healthcare administrative databases, we identified patients with prostate cancer who used an NHA (abiraterone or enzalutamide) after androgen deprivation therapy and who died between 2012 and 2016. The primary outcome was the use of an NHA in the 30 days before death. Use of an NHA in the 60 and 90 days before dying, and initiation (first prescription) of an NHA in the 30 days before death were evaluated as secondary outcomes. Multivariable analysis of the primary outcome was performed with logistic regression with results reported as odds ratios (OR) with 95% confidence intervals (95%CI). Results: The cohort consists of 1316 patients who used an NHA over the course of their disease and died at a median age of 78 years old, with 292 (22.2%), 464 (35.3%), and 575 (43.7%) having used an NHA in the 30, 60 and 90 days of life, respectively. Use of NHA 30 days before dying decreased over the study period, from 44.8% in 2012 to 17.0% in 2016 (Cochran-Armitage test p-value < 0.001). On multivariable analyses, later years of death remained associated with lower odds of NHA use 30 days before death (OR 0.74, 95%CI 0.66 to 0.81, p < 0.001). Fifty-eight (4.4%) patients initiated a NHA 30 days before dying. Conclusions: Rates of NHA use 30 days before dying were high initially but decreased over the study period. Further assessment of NHA use at the end of life is warranted to examine if the trend will be maintained given the recent approval of additional oral NHAs for prostate cancer.

38 Background: Androgen deprivation therapy (ADT) is a cornerstone of advanced prostate cancer (PCa) treatment, however several side-effects are associated with its long-term use. Notably, loss of bone mineral density (BMD) is accelerated which increases fracture risk. Guidelines recommend BMD testing when initiating ADT to properly assess baseline fracture risk. The objective was to examine the proportion of BMD testing in men initiating long-term ADT in Quebec. Methods: The cohort consists of men extracted from Quebec public healthcare insurance administrative databases who were diagnosed with PCa from 2001-2012 and treated by ADT for at least one continuous year. The primary study outcome was the receipt of baseline BMD testing (defined as a BMD test identified in the period from 6 months prior to and up to 12 months after ADT initiation). Multivariable generalized linear mixed with a logit link was performed to identify variables associated with baseline BMD testing accounting for physician clustering. Results: We identified 7,069 patients, of which 887 (12.6%) underwent baseline BMD testing. Baseline BMD testing varied by year of ADT initiation, from 7.7% in 2001-2003 to 12.3% in 2013-2012. Following multivariable analyses, later years of ADT initiation (2004-2006, 2007-2009, 2010-2012, 2013-2015) remained associated with higher odds of baseline BMD testing compared to the earlier years (2001-2003) (ORs ranging from 1.43-1.88; p < 0.001). Conversely, age > 80 (OR 0.73; 95% CI 0.57-0.94; p = 0.001), greater Charlson comorbidity score (OR 0.51; 95%CI 0.34-0.75; p = 0.001), and rural residence (OR 0.60; 95%CI 0.48-0.75; p < 0.001) were associated with lower odds of baseline BMD testing. Conclusions: In our study population, rates of baseline BMD testing in men initiating ADT are low, although the rates increased over the course of the study period. Potential gaps identified in baseline BMD testing include older, more comorbid patients, and rural residence. Additional efforts emphasizing the importance of BMD testing in PCa guidelines may be needed.

161 Background: Canadian Urological Association guidelines outline the scheduling of imaging modalities based on prostate-specific antigen doubling time (PSADT) to screen for mets in pts with nonmetastatic (M0) CRPC and to manage pts with metastatic (M1) CRPC. Data describing guideline adoption and real-world timing of bone scans and treatment patterns in Canadian CRPC pts are limited. Methods: A retrospective chart review conducted at 13 Canadian urology practices included pts with CRPC (PSA ≥2 ng/mL despite androgen deprivation therapy) sequentially identified in reverse chronological order starting July 30, 2015. Pts had no mets at CRPC diagnosis (index date). Data were abstracted from the index date to the chart review date. Coprimary objectives were to describe CRPC management in terms of timing of the 1st and repeat bone scans in M0 and treatment patterns when pts became metastatic. Secondary objectives described nonbone imaging. Results: 232 pts enrolled. Over the observation period 109 remained nonmetastatic (M0 cohort); 123 developed mets (M1 cohort). Median index PSADT was ~1.5x greater for the M0 cohort than the M1 cohort. 68 pts (71.6%) in M0 and 117 pts (95.1%) in M1 had ≥1 bone scan. Median (95% CI) months from CRPC diagnosis to 1st bone scan was 7.5 (5.6–9.6) for pts in M1 and 15.7 (10.0–23.0) for pts in M0. Median (95% CI) months from identification of mets to start of treatment for the M1 cohort was 3.2 (2.3–5.7). The most common therapies were abiraterone (55%) and enzalutamide (42%), with respective median (95% CI) durations of 12.7 (8.7–23.3) and 15.7 months (10.4–NE). 25% of pts received a bone-targeted agent. Conclusions: In CRPC, time to first bone scan was shorter for pts who subsequently developed mets or had rapid PSADT. Abiraterone and enzalutamide were the most common therapies in pts with mets. [Table: see text]

80 Background: The CPCBN has assembled a TMA-based resource comprising the specimens of 1512 prostate cancer patients treated by radical prostatectomy. This richly annotated and multi-institutional resource is available to researchers who wish to access a large cohort to validate prognostic biomarkers (http://www.tfri.ca/en/research/translational-research/cpcbn.aspx). Over the last decade, our laboratory demonstrated with an independent cohort (Gannon PO, et al. Eur J Cancer. 2013 Jul;49(10):2441-8, Labouba I, et al. PLoS One. 2015 Jul 17;10(7):e0131024), the reproducible association of nuclear factor-kappa B (NF-kB) p65 with patient’s risk of biochemical recurrence. Here, we evaluated the CPCBN TMA-series for p65 expression. Methods: Two independent observers scored the frequency of p65 nuclear localisation on digital images obtained after automated immunohistochemistry analysis of p65. Over the available minimum 3 cores of tumour tissue per patient, an average percentage of positive nucleus frequency was used. Statistical analyses were performed using SPSS software. Results: High nuclear frequency of NF-kB p65 (cut-off at 3%) was associated with an increased risk for patients to experience a biochemical relapse (p < 0.001; Exp(B) = 1.599; 95%CI = 1.321-1.937), develop bone metastasis (p = 0.007; Exp(B) = 2.126; 95%CI = 1.234-3.663)and die from their disease (p = 0.001; Exp(B) = 3.117; 95%CI = 1.55-6.266). In multivariate analyses, p65 also remained independent from clinical parameters (PSA, Gleason score and pTNM): biochemical relapse (p = 0.005; Exp(B) = 1.331; 95%CI = 1.092-1.623), bone metastasis (p = 0.033; Exp(B) = 1.82; 95%CI = 1.04- 3.158), mortality (p = 0.007; Exp(B) = 2.626; 95%CI = 1.298-5.312) Conclusions: Using a large cohort of Canadian men, our study reiterates the previous study linking NF-kB p65 with prostate cancer progression and highlights the suitability of CPCBN TMAs for biomarker validation. Our results also reveal the role of p65 as a predictor of bone metastasis development and prostate cancer-specific mortality.

PURPOSE We report our experience with simultaneous resection of residual masses above and below the diaphragm in patients with metastatic nomseminomatous germ cell tumor (NSGCT) of the testis. MATERIALS AND METHODS Twenty-four patients underwent simultaneous resection of residual postchemotherapy masses in the retroperitoneum and chest, including three who also had radical neck dissection. All had been heavily pretreated with chemotherapy and five had undergone previous retroperitoneal lymph node dissections (RPLNDs). RESULTS The combined procedure was performed with no mortality and low morbidity. The median length of the procedure was 5 hours 45 minutes, median blood loss 500 mL, and median length of hospital stay 9 days. Complications included one patient with chylous ascites and one with a prolonged air leak, both of which resolved with conservative management. Eighteen patients had similar pathologic findings in all sites: 13 with necrosis only and five with teratoma only. Six patients had discordant pathology in the abdomen and chest, including one with viable tumor in the chest only and two with viable tumor in the abdomen only. The overall actuarial 5-year survival rate for all patients was 79%. CONCLUSION Simultaneous resection of neck, chest, and abdominal residual masses after chemotherapy for germ cell tumors is both a feasible and safe alternative to staged excision in selected patients who require surgical intervention at multiple sites and fulfills the objective of rendering patients disease-free in a single operative procedure.

e16010 Background: The importance of androgen deprivation therapy (ADT) for the treatment of advanced prostate cancer has been recognized for more than seven decades. However, given that androgens ...

e16131 Background: The use of androgen deprivation therapy (ADT) has been associated with an increased risk of venous thromboembolism (VTE) in patients with prostate cancer, but data remain limited. Methods: A population-based cohort of 21,729 men newly-diagnosed with prostate cancer between 1998 and 2014 was identified using the United Kingdom Clinical Practice Research Datalink linked to the Hospital Episode Statistics database. Time-dependent Cox proportional hazards models were used to estimate adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) of hospitalized VTE associated with current and past ADT use, compared with non-use. A secondary analysis was conducted to assess the risk with current use of specific types of ADT. Results: During a mean follow-up of 4.1 years, there were a total of 609 hospitalized incident VTEs. Compared with non-use, current ADT use was associated with a two-fold increased risk of VTE (incidence rates: 10.1 vs 4.8 per 1000 persons per year; HR: 1.99; 95% CI: 1...

226 Background: Prostate cancer (PCa) death is mainly due to castration-resistant PCa (CRPC) which results from disease progression despite androgen ablation therapy (ADT). Little is known about clinical outcomes and trends of real-life CRPC management in the present era, which has become very complex. Our study aimed to analyze healthcare services use, clinical outcomes and survival trends in real-life management of CRPC in Quebec, Canada. Methods: The study cohort consisted of 7,123 patients which shown evidence of CRPC from January/2001 to July/2013, selected from the public healthcare insurance programs the Régie de l’Assurance Maladie du Québec (RAMQ) databases. Survival was evaluated by Kaplan-Maier and the difference in survival between pre-/post-docetaxel (Doc) (2002-2005 vs 2008-2011) era by log-rank test. The association between Doc exposure and survival was evaluated by Cox proportional hazards model adjusted for several co-variables. Results: Chemotherapy was offered to 17% of patients, while 45% were kept on maximal androgen blockade (MAB) alone, or offered Abiraterone (3%). Androgen targeted therapies (MAB or Abiraterone) were the treatment of choice for the elderly population (mean age 78.8 and 78 ±7, respectively) while chemotherapy was offered to younger patients (mean age 72 ±7.3). Survival rates at 1 and 2 years after the initiation of chemotherapy were 52% and 26% in post-Doc era vs 46% and 17% in the pre-Doc period. In patients receiving first line chemotherapy only, hospitalization due to PCa was a poor prognostic predictor (HR: 2.0; 95%CI: 1.5-2.6), as expected. In addition among patients without previous hospitalization the risk of death was higher in the pre- vs post-Doc era (HR: 1.7 CI: 1.003-2.851). Conclusions: Patient age seems to be a strong determinant in CRPC therapy selection. In patients without serious complications leading to hospitalization, survival was greatly improved in the post-Doc era. Our data also supports that patients older than those in the TAX327 trial (72 vs 68) may equally benefit from chemotherapy. This is encouraging as we hope to observe comparable results for new approved therapies for CRPC.

e16029 Background: Medical or surgical castration are the treatments of choice for hormone-sensitive prostate cancer with a high-risk of disease recurrence or progression. In addition, androgen abl...

83 Background: We present the long-term results of a cohort of patients with intermediate-risk prostate cancer (PC) treated with single fraction high-dose-rate brachytherapy (HDRB) combined with hypofractionated external beam radiation therapy (HRT). Methods: Patients with intermediate-risk PC were treated exclusively with HDRB and HRT. HDRB delivered a dose of 10 Gy to the prostate gland and HRT consisted of 50 Gy delivered in 20 daily fractions. The planning target volume was the prostate gland with a 1 cm margin all around. The first 121 consecutive patients with a minimum of 2 years post-treatment follow-up were assessed for acute and chronic toxicity and disease control. Results: The median follow-up was 62.8 months. No acute grade III or higher toxicities were seen. Grade II late GI toxicity was seen in 9 patients (7.4%) and grade III in 2 (1.6%). Grade 3 GU toxicity was seen in 2 patients (1.6%), both with urinary obstructive symptoms requiring catheterization. A repeat biopsy was offered to the first 58 consecutively treated patients, and 44 patients agreed with the procedure. A negative biopsy was found in 40 patients (91%). The biochemical relapse-free survival rate at 5 and 8 years were 90.7% and 81.4%, with 13 patients presenting biochemical failure. Among them, nine were diagnosed with distant metastasis. Prostate cancer-specific and overall survival rates at 8 years were 100% and 95.5%, respectively. Conclusions: Our program of HDRB and HRT is well tolerated, with acceptable toxicity rates. Furthermore, results from re-biopsies revealed an elevated rate of local control. These results are encouraging and confirm that the use of conformal RT techniques, adapted to specific biological features, have the potential to improve the therapeutic ratio in intermediate risk PC patients. No significant financial relationships to disclose.