Chronic prednisone, metformin, and nonsteroidal anti-inflammatory drug use and clinical outcome in a cohort of bladder cancer patients undergoing radical cystectomy in Québec, Canada.

BACKGROUND: Studies have suggested a positive association between bladder cancer (BC) outcome and comedication use, including nonsteroidal anti-inflammatory drugs (NSAID), metformin, and prednisone use. To validate these associations, we evaluated whether these medications were associated with clinical outcome in a Canadian cohort of BC patients. METHODS: This is a retrospective cohort study on BC patients undergoing radical cystectomy (RC) in Québec province in 2000-2015, as registered in the provincial health administration databases. Medication use was considered chronic when prescribed for ≥ 1 year. Overall (OS), disease-specific (DSS) and recurrence-free (RFS) survival were compared using multivariable Cox proportional hazards models. Covariates included age, Charlson's comorbidity index, region of residence, year of RC, distance to hospital, hospital type, hospital and surgeon annual RC volume, neoadjuvant chemotherapy use, and type of bladder diversion, as well as mutual adjustment for concomitant comedication use (statins, NSAIDs, metformin, and prednisone). RESULTS: Of 3742 patients included, 293, 420, and 1503 patients chronically used prednisone, metformin, and NSAIDs before surgery, respectively. In multivariable analyses, preoperative prednisone use was associated with improved OS (HR 0.67, 95%CI 0.55-0.82), DSS (HR 0.58, 95%CI 0.45-0.76), and RFS (HR 0.61, 95%CI 0.47-0.78). Patients who chronically used metformin preoperatively had a worse OS (HR 1.29, 95%CI 1.07-1.55), DSS (HR 1.38, 95%CI 1.10-1.72), and RFS (HR 1.41, 95%CI 1.13-1.74). Preoperative, chronic NSAID use was not significantly associated with all clinical outcomes, with adjusted HRs for OS, DSS, and RFS of 1.10 (95%CI 0.95-1.27), 1.24 (95%CI 1.03-1.48), and 1.22 (95%CI 1.03-1.45), respectively. Directionality of findings was similar when stratifying by comedication use in the year following surgery. Results were similar after propensity-score matching too. CONCLUSIONS: In our Canadian cohort of BC undergoing RC, chronic prednisone use was associated with improved clinical outcomes, while metformin and NSAID were not.

A DNA copy number alteration classifier as a prognostic tool for prostate cancer patients.

BACKGROUND: Distinguishing between true indolent and potentially life-threatening prostate cancer is challenging in tumours displaying clinicopathologic features associated with low or intermediate risk of relapse. Several somatic DNA copy number alterations (CNAs) have been identified as potential prognostic biomarkers, but the standard cytogenetic method to assess them has a limited multiplexing capability. METHODS: Multiplex ligation-dependent probe amplification (MLPA) targeting 14 genes was optimised to survey 448 tumours of patients with low or intermediate risk (Grade Group 1-3, Gleason score ≤7) who underwent radical prostatectomy. A 6-gene CNA classifier was developed using random survival forest and Cox proportional hazard modelling to predict biochemical recurrence. RESULTS: The classifier score was significantly associated with biochemical recurrence after adjusting for standard clinicopathologic variables and the known prognostic index CAPRA-S score with a hazard ratio of 2.17 and 1.80, respectively (n = 406, P < 0.01). The prognostic value of this classifier was externally validated in published CNA data from three radical prostatectomy cohorts and one radiation therapy pre-treatment biopsy cohort. CONCLUSION: The 6-gene CNA classifier generated by a single MLPA assay compatible with the small quantities of DNA extracted from formalin-fixed paraffin-embedded (FFPE) tissue specimens has the potential to improve the clinical management of patients with low or intermediate risk disease.

Androgen Deprivation Therapy and Risk of Cardiovascular Disease in Patients With Prostate Cancer Based on Existence of Cardiovascular Risk.

BACKGROUND: Controversy exists regarding the risk of cardiovascular disease (CVD) associated with androgen deprivation therapy (ADT) in patients with prostate cancer. We sought to evaluate the association between gonadotropin-releasing hormone (GnRH) agonists versus GnRH antagonist and the risk of CVD in patients with prostate cancer with or without prior CVD. PATIENTS AND METHODS: Using administrative databases from Quebec, Canada, we identified first-time GnRH agonists and antagonist (degarelix) users between January 2012 and June 2016. Follow-up ended at the earliest of the following: first CVD event (myocardial infarction [MI], stroke, ischemic heart disease [IHD], arrhythmia, and heart failure [HF]); switch of GnRH group; death; or December 31, 2016. Inverse probability of treatment weighting (IPTW) based on the propensity score was used to control for potential confounding. IPTW-Cox proportional hazards model accounting for competing risks was used to evaluate the association of interest. RESULTS: Among 10,785 patients identified, 10,201 and 584 were on GnRH agonists and antagonist, respectively. Median age was 75 years (interquartile range, 69-81 years) for both groups. A total of 4,152 (40.7%) men in the GnRH agonists group and 281 (48.1%) men in the GnRH antagonist group had CVD in the 3-year period prior to ADT initiation. Risk of HF was decreased in the antagonist group compared with the GnRH agonist group among patients with prior CVD (hazard ratio [HR], 0.46; 95% CI, 0.26-0.79). Risk of IHD was decreased in the antagonist group in patients without prior CVD (HR, 0.26; 95% CI, 0.11-0.65). Use of antagonist was associated with an increased risk of arrhythmia among patients with no prior CVD (HR, 2.34; 95% CI, 1.63-3.36). CONCLUSIONS: Compared with GnRH agonists, the GnRH antagonist was found to be associated with a decreased risk of HF, specifically among patients with prior CVD. Among those with no prior CVD, the GnRH antagonist was associated with a decreased risk of IHD but an increased risk of arrhythmia.

Utilization Trends of Novel Hormonal Agents in Metastatic Castration-Resistant Prostate Cancer in Quebec.

BACKGROUND: The introduction of novel hormonal agents (NHAs) such as abiraterone acetate (ABI) and enzalutamide (ENZ) for metastatic castration-resistant prostate cancer (mCRPC) was an important milestone given their survival benefits, tolerability, and ease of administration relative to taxane chemotherapies. This descriptive study sought to describe the utilization trends of ABI and ENZ in patients with mCRPC in the early years after their approval in the province of Quebec in Canada. METHODS: A retrospective population-based cohort was extracted from Quebec public healthcare administrative databases. The cohort included first-time users of NHAs (ABI or ENZ) from 2011 to 2016. The primary analyses aimed to describe the overall temporal trends (2011-2016) of NHA initiators by chemotherapy status (chemotherapy-naïve versus post-chemotherapy), and prescribing specialty (medical oncology versus urology versus others). RESULTS: The cohort comprised 2183 patients, with 1562 (72%) in the chemotherapy-naïve group and 621 (28%) in the post-chemotherapy group. While the majority of patients were post-chemotherapy NHA initiators in 2012, this proportion decreased over time and accounted for only 13% of NHA initiators by the end of 2016. Medical oncologists were the most frequent prescribers of NHAs (upwards of 60%) throughout 2012 but fell to 45% by the end of 2016. Conversely, the proportion of prescriptions by urologists increased from 22% in 2012 to 42% in 2016. CONCLUSION: Over time, there was an increasing proportion of (1) patients who initiated NHAs without prior chemotherapy treatment, (2) NHA prescribing by urologists, and (3) ENZ users. Taken together, this implies that the introduction of NHAs has altered the management of mCRPC and urologists quickly adopted NHAs into their practice.

The Health Economics of Metastatic Hormone-Sensitive and Non-Metastatic Castration-Resistant Prostate Cancer-A Systematic Literature Review with Application to the Canadian Context.

Background: Health economic evaluations are needed to assess the impact on the healthcare system of emerging treatment patterns for advanced prostate cancer. The objective of this study is to review the scientific literature identifying cost-effectiveness and cost analyses that are assessing treatments for metastatic hormone-sensitive prostate cancer (mHSPC) and nonmetastatic castration-resistant prostate cancer (nmCRPC). Methods: On 29 June 2021, we searched the scientific (MEDLINE, Embase, and EBSCO) and grey literature for health economic studies targeting mHSPC and nmCRPC. We used the CHEC-extended checklist and the Welte checklist for risk-of-bias assessment and transferability analysis, respectively. Results: We retained 20 cost-effectiveness and 4 cost analyses in the mHSPC setting, and 14 cost-effectiveness and 6 cost analyses in the nmCRPC setting. Docetaxel in combination with androgen deprivation therapy (ADT) was the most cost-effective treatment in the mHSPC setting. Apalutamide, darolutamide, and enzalutamide presented similar results vs. ADT alone and were identified as cost-effective treatments for nmCRPC. An increase in costs as patients transitioned from nmCRPC to mCRPC was noted. Conclusions: We concluded that there is an important unmet need for health economic evaluations in the mHSPC and nmCRPC setting incorporating real-world data to support healthcare decision making.

Fatty acid oxidation enzyme Δ3, Δ2-enoyl-CoA isomerase 1 (ECI1) drives aggressive tumor phenotype and predicts poor clinical outcome in prostate cancer patients.

Prostate cancer (PCa) metastases are highly enriched with genomic alterations including a gain at the 16p13.3 locus, recently shown to be associated with disease progression and poor clinical outcome. ECI1, residing at the 16p13.3 gain region, encodes Δ3, Δ2-Enoyl-CoA Delta Isomerase 1 (ECI1), a key mitochondrial fatty acid ß-oxidation enzyme. Although deregulated mitochondrial fatty acid ß-oxidation is known to drive PCa pathogenesis, the role of ECI1 in PCa is still unknown. We investigated the impacts of ECI1 on PCa phenotype in vitro and in vivo by modulating its expression in cell lines and assessed the clinical implications of its expression in human prostate tissue samples. In vitro, ECI1 overexpression increased PCa cell growth while ECI1 deficiency reduced its growth. ECI1 also enhanced colony formation, cell motility, and maximal mitochondrial respiratory capacity. In vivo, PCa cells stably overexpressing ECI1 injected orthotopically in nude mice formed larger prostate tumors with higher number of metastases. Immunohistochemistry analysis of the human tissue microarray representing 332 radical prostatectomy cases revealed a stronger ECI1 staining in prostate tumors compared to corresponding benign tissues. ECI1 expression varied amongst tumors and was higher in cases with 16p13.3 gain, high Gleason grade, and advanced tumor stage. ECI1 overexpression was a strong independent predictor of biochemical recurrence after adjusting for known clinicopathologic parameters (hazard ratio: 3.65, P < 0.001) or the established CAPRA-S score (hazard ratio: 3.95, P < 0.001). ECI1 overexpression was also associated with significant increased risk of distant metastasis and reduced overall survival. Overall, this study demonstrates the functional capacity of ECI1 in PCa progression and highlights the clinical implication of ECI1 as a potential target for the management of PCa.

Comparative Cardiovascular Safety of Novel Hormonal Agents in Metastatic Castration-Resistant Prostate Cancer Using Real-World Data.

BACKGROUND: Novel hormonal agents (NHAs) such as abiraterone acetate (ABI) and enzalutamide (ENZ) are frequently used in metastatic castration-resistant prostate cancer (mCRPC). Despite their 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 ENZ in patients with mCRPC in the real-world. METHODS: A retrospective population-based cohort was extracted from Quebec public healthcare administrative databases. First-time NHA users between 2011 and 2016 were selected. The primary outcome of interest was cardiovascular-related hospitalization (composite outcome that included acute coronary syndrome, cerebrovascular stroke, heart failure, arrhythmia and others). Inverse probability of treatment weighting (IPTW) with the propensity score was used to adjust for measured baseline characteristics 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 ENZ group. Crude incidence rates of cardiovascular-related hospitalization were of 9.8 events per 100 person-years (PYs) and of 7.1 events per 100 PYs for the ABI and ENZ groups, respectively. The ABI group was at greater risk of cardiovascular-related hospitalization compared to the ENZ group (IPTW-hazard ratio (HR) 1.82; 95% confidence interval (95%CI) 1.09-3.05). The risk of hospitalization for heart failure was greater in ABI (IPTW-HR 2.88; 95%CI 1.09-7.63). CONCLUSIONS: Our findings suggest that ABI users may be at greater risk of cardiovascular-related hospitalization compared to ENZ users, in particular for heart failure. 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.

The Use of 5-Alpha Reductase Inhibitors and Alpha-1 Blockers Does Not Improve Clinical Outcome in Male Patients Undergoing Radical Cystectomy for Bladder Cancer in Quebec, Canada.

BACKGROUND: Existing literature suggests that bladder cancer (BC) outcome may be improved when patients use 5α-reductase inhibitors and/or α1-blockers, but such a conclusion may be subject to publication bias. We evaluated whether preoperative use of 5α-reductase inhibitors or α1-blockers was associated with improved clinical outcomes in a cohort of patients with BC undergoing radical cystectomy (RC). PATIENTS AND METHODS: Using provincial health administrative databases, we retrospectively identified male BC patients undergoing RC in Quebec province between 2000 and 2015, and we collected data from 2 years before RC until December 2016 or death. Survival analyses were conducted using Kaplan-Meier curves, log-rank tests, propensity score matching, and uni- and multivariable Cox proportional hazards models. Covariates included age, Charlson's comorbidity index, region of residence, year of RC, distance to hospital, hospital type, annual RC volume of each hospital and surgeon, neoadjuvant chemotherapy use, and type of bladder diversion. RESULTS: Of the 2822 patients included, 284 patients used 5α-reductase inhibitors and 1001 patients used α1-blockers prior to surgery. Median follow-up time was 7.7 years. Patients who used 5α-reductase inhibitors or α1-blockers were generally older, had more comorbidities, and were treated more recently in academic centers. Overall, bladder cancer-specific and recurrence-free survival did not differ significantly between those using 5α-reductase inhibitors prior to surgery and controls who never used 5α-reductase inhibitors. Adjusted hazard ratios were 1.03 (95% confidence interval [CI], 0.88-1.21) for overall survival, 1.12 (95% CI, 0.92-1.36) for bladder cancer-specific survival, and 1.19 (95% CI, 0.99-1.42) for recurrence-free survival. The aforementioned outcomes were significantly worse in patients who used α1-blockers prior to surgery compared to controls, with respective adjusted hazard ratios of 1.15 (95% CI, 1.04-1.27), 1.19 (95% CI, 1.05-1.35), and 1.18 (95% CI, 1.05-1.33). CONCLUSION: Preoperative use of 5α-reductase inhibitors and α1-blockers did not improve clinical outcome in our cohort of male patients undergoing radical cystectomy for bladder cancer.

Contemporary Population-Based Analysis of Bone Mineral Density Testing in Men Initiating Androgen Deprivation Therapy for Prostate Cancer.

BACKGROUND: Androgen deprivation therapy (ADT) is a cornerstone of treatment for advanced prostate cancer (PCa); however, it accelerates the loss of bone mineral density (BMD), which increases fracture risk. Guidelines recommend BMD testing when initiating ADT to assess baseline fracture risk properly. The objective of this study was to examine the proportion of BMD testing in men initiating ADT in Quebec and to identify factors associated with receipt of this testing. METHODS: The study cohort consisted of men extracted from Quebec public healthcare insurance administrative databases who initiated continuous ADT from 2000 to 2015 for >12 months. The primary study outcome was receipt of BMD testing in the period from 6 months before through 12 months after ADT initiation. Multivariable generalized linear mixed regression modeling with a logit link was performed to identify variables associated with BMD testing. RESULTS: We identified 22,033 patients, of whom 3,910 (17.8%) underwent BMD testing. Rates of BMD testing increased from 4.1% in 2000 to 23.4% in 2015. After multivariable analyses, prior history of osteoporosis (odds ratio [OR], 1.84; 95% CI, 1.32-2.57; P<.001), rheumatoid arthritis (OR, 1.64; 95% CI, 1.15-2.34; P=.006), use of bisphosphonates (OR, 1.47; 95% CI, 1.25-1.73; P<.001), and long-term corticosteroid use (OR, 1.63; 95% CI, 1.15-2.31; P=.006) were associated with higher odds of BMD testing. Patient age >80 years (OR, 0.67; 95% CI, 0.59-0.76; P<.001), metastases (OR, 0.79; 95% CI, 0.70-0.89; P<.001), higher Charlson comorbidity score (OR, 0.65; 95% CI, 0.51-0.81; P<.001), and rural residence (OR, 0.77; 95% CI, 0.68-0.87; P<.001) were associated with lower odds of BMD testing. CONCLUSIONS: In our study population, BMD testing rates in men initiating ADT were low, although they increased over the years especially in the years after the publication of recommendations for BMD testing in these patients. Potential gaps identified include being older, more comorbid, and rural areas. Overall, additional efforts emphasizing the importance of BMD testing in PCa guidelines may be needed.

Design and Development of a Fully Synthetic Multiplex Ligation-Dependent Probe Amplification-Based Probe Mix for Detection of Copy Number Alterations in Prostate Cancer Formalin-Fixed, Paraffin-Embedded Tissue Samples.

DNA copy number alterations (CNAs) are promising biomarkers to predict prostate cancer (PCa) outcome. However, fluorescence in situ hybridization (FISH) cannot assess complex CNA signatures because of low multiplexing capabilities. Multiplex ligation-dependent probe amplification (MLPA) can detect multiple CNAs in a single PCR assay, but PCa-specific probe mixes available commercially are lacking. Synthetic MLPA probes were designed to target 10 CNAs relevant to PCa: 5q15-21.1 (CHD1), 6q15 (MAP3K7), 8p21.2 (NKX3-1), 8q24.21 (MYC), 10q23.31 (PTEN), 12p13.1 (CDKN1B), 13q14.2 (RB1), 16p13.3 (PDPK1), 16q23.1 (GABARAPL2), and 17p13.1 (TP53), with 9 control probes. In cell lines, CNAs were detected when the cancer genome was as low as 30%. Compared with FISH in radical prostatectomy formalin-fixed, paraffin-embedded samples (n = 18: 15 cancers and 3 matched benign), the MLPA assay showed median sensitivity and specificity of 80% and 93%, respectively, across all CNAs assessed. In the validation set (n = 40: 20 tumors sampled in two areas), the respective sensitivity and specificity of MLPA compared advantageously with FISH and TaqMan droplet digital PCR (ddPCR) when assessing PTEN deletion (FISH: 85% and 100%; ddPCR: 100% and 83%) and PDPK1 gain (FISH: 100% and 92%; ddPCR: 93% and 100%). This new PCa probe mix accurately identifies CNAs by MLPA across multiple genes using low quality and quantities (50 ng) of DNA extracted from clinical formalin-fixed, paraffin-embedded samples.

Are basic robotic surgical skills transferable from the simulator to the operating room? A randomized, prospective, educational study.

INTRODUCTION: We aimed to assess the transferability of basic robotic skills from the simulator to the operating room (OR) while performing robotic-assisted radical prostatectomy (RARP). METHODS: Fourteen urology residents were randomized into two groups: group A was required to practice three sessions (nine tasks each) on the simulator, whereas group B was required to practice (same nine tasks) until they reached competency. Both groups were recorded while practicing on the da Vinci Surgical Skills Simulator. Both groups were then recorded while performing bladder mobilization during RARP. Senior residents from both groups were also recorded while performing urethro-vesical anastomosis during RARP. Recordings were assessed blindly using the validated Global Evaluative Assessment of Robotic Skills (GEARS) tool by C-SATS. Spearman's correlation coefficient (rho) was used to assess correlation between GEARS scores from practice sessions on the da Vinci Simulator and the GEARS scores from bladder mobilization and urethro-vesical anastomosis during RARP. RESULTS: There was no difference in total GEARS scores between the two groups in the OR. Total GEARS scores for "ring and rail 2" and "suture sponge" tasks correlated with the total GEARS scores during urethro-vesical anastomosis (rho=0.86, p=0.007; rho=0.90, p=0.002, respectively). GEARS' efficiency component during "energy and dissection" task on the da Vinci Simulator correlated with GEARS' efficiency component during bladder mobilization (rho=0.62, p=0.03). GEARS' force sensitivity component during "ring and rail 2" and "dots and needles" tasks on the da Vinci Simulator correlated with GEARS' force sensitivity component during bladder mobilization (rho=0.58, p=0.047; rho =0.65, p=0.02, respectively). CONCLUSIONS: Objective assessments of urology residents on the da Vinci Surgical Skills Simulator tasks ring and rail 2 and suture sponge correlated with their objective assessments of bladder mobilization and urethro-vesical anastomosis. Therefore, basic robotic skills could be transferred from the simulator to the OR.

Impact of the introduction of novel hormonal agents on metastatic castration-resistant prostate cancer treatment choice.

BACKGROUND: Docetaxel-based chemotherapy has been the cornerstone of the management of symptomatic metastatic castration-resistant prostate cancer (mCRPC) since 2004. This study aimed to describe how real-world clinical practice was changed with the public funding of novel hormonal agents (abiraterone and enzalutamide) in Quebec. METHODS: We conducted a retrospective cohort study in two McGill University hospitals. Hospital-based cancer registries were used to select mCRPC patients in medical oncology departments from January 2010 to June 2014. Two groups according to mCRPC diagnosis year were built, with 2012 chosen as the cut-off year, corresponding to the year abiraterone was approved for public reimbursement in second-line in Quebec. Kaplan-Meier analysis was used to estimate time to first docetaxel prescription since mCRPC diagnosis before and after 2012. Cox regression was used to identify predictive factors of docetaxel and novel hormonal agent use. RESULTS: In our cohort, 308 patients diagnosed with mCRPC were selected with 162 patients in the pre-2012 group and 146 patients in the post-2012 group. The median age at mCRPC was 74.0 years old. At 12 months from diagnosis, 69% of patients received a prescription for docetaxel in the pre-2012 group comparatively to 53% in the post-2012 group. Factors that decreased the likelihood of docetaxel utilization were: age older than 80 at mCRPC diagnosis (HR: 0.5; 95%CI: 0.3-0.7), mCRPC diagnosis after 2012 (HR: 0.6; 95%CI: 0.4-0.8), and asymptomatic disease at mCRPC diagnosis (HR: 0.5; 95%CI: 0.3-0.7). CONCLUSION: The introduction of novel hormonal agents reduced first-line and overall docetaxel utilization and delayed time to its initiation.

The use of perioperative chemotherapy in patients undergoing radical cystectomy for bladder cancer in Quebec, Canada, 2000-2016.

INTRODUCTION: Despite its proven benefit, studies have reported poor use of perioperative chemotherapy (POC) in bladder cancer patients undergoing radical cystectomy (RC). We evaluated POC use in Quebec between January 2000 and September 2016. METHODS: Using provincial health administrative databases, data were retrospectively collected from patients from two years before RC until December 2016 or death. Logistic regression was used to identify variables predicting POC use. Survival analyses were conducted using Cox regression. Analyzed covariates were age, sex, comorbidities, year of RC, residence and hospital region, distance to hospital, hospital type and size, and hospital's and surgeon's RC volume. RESULTS: A total of 790/4656 patients (17.0%) received POC. Neoadjuvant chemotherapy (NAC) use increased in recent years: 3.5% (2009), 11.2% (2012), and 20.7% (2015). POC use was increased in patients with recent surgery, a younger age, less comorbidities, residing closer to the hospital of surgery, and a high surgeon's RC volume (p<0.05). For patients treated between 2013 and 2016, a younger age (odds ratio [OR] 0.71; 95% confidence interval [CI] 0.64-0.80 per five years), shorter distance to the hospital (OR 0.88; 95% CI 0.77-0.99 per 50 km), surgery in an academic hospital (OR 1.86; 95% CI 1.06-3.29), and recent surgery (OR 1.34; 95% CI 1.14-1.58 per year) independently predicted NAC use. These NAC users had a significantly higher overall survival rate than patients without POC (hazard ratio 0.73; 95% CI 0.55-0.97). Limitations include missing data on pathological staging. CONCLUSIONS: NAC/POC use increased in Quebec but was lower compared to most developed countries. Its use was lower in patients residing further from the hospital and in those treated in non-academic hospitals.

Improving ultrasound-based prostate volume estimation.

BACKGROUND: To define a new coefficient to be used in the formula (Volume = L x H x W x Coefficient) that better estimates prostate volume using dimensions of fresh prostates from patients who had transrectal ultrasound (TRUS) imaging prior to prostatectomy. METHODS: The prostate was obtained from 153 patients, weighed and measured to obtain length (L), height (H), and width (W). The density was determined by water displacement to calculate volume. TRUS data were retrieved from patient charts. Linear regression analyses were performed to compare various prostate volume formulas, including the commonly used ellipsoid formula and newly introduced bullet-shaped formula. RESULTS: By relating measured prostate volumes from fresh prostates to TRUS-estimated prostate volumes, 0.66 was the best fitting coefficient in the (L x H x W x Coefficient) equation. This newfound coefficient combined with outlier removal yielded a linear equation with an R2 of 0.64, compared to 0.55 and 0.60, for the ellipsoid and bullet, respectively. By comparing each of the measured vs. estimated dimensions, we observed that the mean prostate height and length were overestimated by 11.1 and 10.8% using ultrasound (p < 0.05), respectively, while the mean width was similar (p > 0.05). Overall, the ellipsoid formula underestimates prostate volumes by 18%, compared to an overestimation of 4.6 and 5.7% for the bullet formula and the formula using our coefficient, respectively. CONCLUSIONS: This study defines, for the first time, a coefficient based on freshly resected prostates as a reference to estimate volumes by imaging. Our findings support a bullet rather than an ellipsoid prostate shape. Moreover, substituting the coefficient commonly used in the ellipsoid formula by our calculated coefficient in the equation estimating prostate volume by TRUS, provides a more accurate value of the true prostate volume.

Cancer Drug Use in the Last Month of Life in Men With Castration-Resistant Prostate Cancer.

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.

Short- and long-term survival has improved after radical cystectomy for bladder cancer in Québec during the years 2000-2015.

BACKGROUND AND OBJECTIVES: We evaluated the short- and long-term outcome in bladder cancer (BC) patients treated with radical cystectomy (RC) in Québec (Canada). METHODS: Data were collected from provincial registries on all BC patients who underwent RC in Québec province in 2000-2015. Outcomes were hospitalization rates and survival. Survival analyses were conducted using log-rank tests and Cox proportional hazards models. RESULTS: In total, 4450 patients were included in our analysis. RC was increasingly conducted by higher-volume surgeons in larger, higher-volume, academic hospitals. Comparing patients treated in 2010-2015 to 2000-2009, recently treated patients had shorter postoperative hospital stays (absolute difference, 0.9 days, P < 0.001) but also a higher readmission rate (25.0% vs 21.1% in the 30 days following discharge, P = 0.003). Overall (5-year rates 50.9% vs 42.7%, P < 0.001) and BC-specific survival (61.3% vs 55.5%, P < 0.001) had significantly improved. In multivariable analyses, overall survival was significantly better in recently treated patients (hazard ratio [HR], 0.66; 95% confidence interval [CI], 0.60-0.73), younger patients (HR, 1.16; 95% CI, 1.14-1.19), patients residing closer to the hospital (HR, 1.03; 95% CI, 1.01-1.06), and patients treated by high-volume surgeons (HR, 0.88; 95% CI, 0.82-0.94). CONCLUSIONS: Survival in BC patients after RC has improved in recent years. Other predictors for survival are younger age, shorter distance between patients' residences and hospitals, and higher surgeon's RC loads.

A Multi-Institutional Validation of Gleason Score Derived from Tissue Microarray Cores.

To test the agreement between high-grade PCa at RP and TMA, and the ability of TMA to predict BCR. Validation of concordance between tissue microarray (TMA) and radical prostatectomy (RP) high-grade prostate cancer (PCa) is crucial because latter determines the treated natural history of PCa. We hypothesized that TMA Gleason score is in agreement with RP pathology and capable of accurately predicting biochemical recurrence (BCR). Data were provided from a multi-institutional Canadian sample of 1333 TMA and RP specimens with complete clinicopathological data. First, rate of agreement between TMA and high-grade Gleason at RP or biopsy and RP was tested. Second, ability of RP, TMA and biopsy to predict BCR was compared. Multivariable (MVA) Cox regression models were fitted and BCR rates were illustrated with Kaplan-Meier plots. Agreement between RP and TMA and between RP and biopsy was 72.6% (95% CI:69.7-75.5) and 60.4% (95% CI:57.2-63.6), respectively. In MVA predicting BCR, the accuracy for RP, TMA and biopsy was 0.73, 0.72 and 0.68, respectively. TMA added discriminatory ability among exclusively low-grade Gleason RP patients (p = 0.02), but did not improve BCR discrimination in exclusive high-grade PCa RP patients (p = 0.8). TMA Gleason grade accurately reflects presence of high-grade Gleason in RP specimen, accurately predicts BCR rates after RP and improves prediction of BCR in low-grade Gleason patients at RP.