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.

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 cost-effectiveness analysis of bladder management strategies in neurogenic lower urinary tract dysfunction after spinal cord injury: A publicly funded health care perspective.

STUDY DESIGN: Economic evaluation study. OBJECTIVES: To investigate the long-term cost-effectiveness of clean intermittent catheterization (CIC) compared with suprapubic catheters (SPC) and indwelling urethral catheters (UC) among individuals with neurogenic lower urinary tract dysfunction (NLUTD) related to spinal cord injury (SCI) from a public healthcare perspective. SETTING: University affiliated hospital in Montreal, Canada. METHODS: A Markov model with Monte Carlo simulation was developed with a cycle length of 1 year and lifetime horizon to estimate the incremental cost per quality-adjusted life years (QALYs). Participants were assigned to treatment with either CIC or SPC or UC. Transition probabilities, efficacy data, and utility values were derived from literature and expert opinion. Costs were obtained from provincial health system and hospital data in Canadian Dollars. The primary outcome was cost per QALY. Probabilistic and one-way deterministic sensitivity analyses were performed. RESULTS: CIC had a lifetime mean total cost of $ 29,161 for 20.91 QALYs. The model predicted that a 40-year-old person with SCI would gain an additional 1.77 QALYs and 1.72 discounted life-years gained if CIC were utilized instead of SPC at an incremental cost savings of $330. CIC confer 1.96 QALYs and 3 discounted life-years gained compared to UC with an incremental cost savings of $2496. A limitation of our analysis is the lack of direct long-term comparisons between different catheter modalities. CONCLUSIONS: CIC appears to be a dominant and more economically attractive bladder management strategy for NLUTD compared with SPC and/or UC from the public payer perspective over a lifetime horizon.

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.

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.

Evaluation of New Tests and Interventions for Prostate Cancer Management: A Systematic Review.

Background: Inaccurate risk classification and the burden of unnecessary biopsies are a challenge due to the limited ability of current risk assessment tools and modalities to diagnose prostate cancer (PCa) and distinguish indolent from aggressive disease. This systematic review assesses newly developed tests and interventions with high evidence of clinical utility that might be adopted in clinical practice during PCa management before initial and repeat biopsy, after positive biopsy, and after radical treatment. Methods: The Cochrane, Embase, MEDLINE, and Web of Science databases were searched for studies pertaining to the clinical utility of PCa diagnostic tests. Outcomes of interest were (1) a measure of the percentage of altered decision-making, (2) decrease in number of unnecessary biopsies, (3) decrease or increase in treatment intensity, and (4) risk reclassification after test results. Results: The search yielded 2,940 articles, of which 46 met the inclusion criteria. We found clinical utility evidence on the Prostate Health Index (PHI), 4Kscore test, MRI, OncotypeDX, Decipher test, Prolaris, ConfirmMDx, Progensa PCA3, NADiA ProsVue, and ProMark. No evidence was identified for Prostarix, ProstaVysion, Prostate Core Mitomic Test, and Mi-Prostate Score. The interventions demonstrated their clinical utility in terms of change in treatment recommendations, decrease/increase in interventional treatment, decrease in biopsy, and risk reclassification. At diagnosis after a positive biopsy, ProMark, OncotypeDX, Prolaris, and MRI guided the use of active surveillance. Use of NADiA ProsVue, Decipher, and Prolaris aided in the decision to add adjuvant therapy post-prostatectomy. PHI, 4Kscore, and MRI used prior initial and repeat biopsies, and ConfirmMDx and Progensa PCA3 used prior repeat biopsies to improve prediction of biopsy outcome, allowing a decrease in unnecessary biopsies. Conclusions: This systematic review suggests that implementation of these tests in clinical practice could effectuate personalized treatment of PCa. Further clinical and economic evaluation studies of long-term PCa outcomes are warranted to provide further guidance.

Changes in the levels of testosterone profile over time in relation to clinical parameters in a cohort of patients with prostate cancer managed by active surveillance.

OBJECTIVES: To characterize testosterone profile changes over time in a cohort of prostate cancer (PCa) patients managed with active surveillance (AS) and to assess its correlation with the initial disease characteristics and further progression. METHODS: We conducted retrospective chart review of PCa patients managed with AS. Patients were followed with PSA, total, free and bioavailable testosterone measurements, physical examination, and by repeat biopsies or periodic magnetic resonance imaging. Disease progression was identified by follow-up biopsy changes or by imaging. A Cox proportional hazard regression models were used to assess the association between testosterone profile at baseline and the risk of progression. RESULTS: For the 122 patients included in analyses, the mean age at diagnosis was 65.8 years; the mean follow-up time was 7.8 years. At baseline, 108 (88.5%) patients had a Gleason score of ≤ 6. In all, 45 (36.8%) patients had disease progression, with a mean time to progression of 4.6 years. During follow-up, PSA levels showed a rising trend, while testosterone profile levels showed a trend of decrease over time. There was no significant correlation between PSA and testosterone profile (total, free, and bioavailable) level changes over time (ρ = - 0.14, - 0.11 and - 0.16, P = 0.16, 0.34, and 0.20, respectively). In addition, multivariable analysis showed that serum-free testosterone was an independent predictor of disease progression (HR 0.93, 95% CI 0.88-0.99, P = 0.029). CONCLUSION: Our study results showed that testosterone profile measurements tended to decrease over time in PCa patients managed with AS. Free testosterone was a significant independent variable of disease progression.

A cost-utility analysis of artificial urinary sphincter versus AdVance male sling in post prostatectomy stress urinary incontinence: A publicly funded health care perspective.

AIMS: To investigate the long-term cost-utility of the artificial urinary sphincter (AUS) compared with Transobturator Retroluminal Sling (AdVance) in the treatment of patients with severe post prostatectomy stress urinary incontinence (PPSUI) from a Canadian provincial health perspective. METHODS: A Markov model with Monte Carlo simulation was developed with a cycle length of 1 year and time horizon up to 10 years to estimate the incremental cost per quality-adjusted life years (QALYs). Patients were assigned to treatment with either AUS or an AdVance sling. Transition probabilities, efficacy data, and utility indices were derived from published literature and expert opinion. Cost data were obtained from provincial health care system and hospital data in 2016-Canadian dollars. The primary outcome was cost per quality-adjusted life year. A standard discount rate of 1.5% was applied annually. Probabilistic and one way deterministic sensitivity analyses were performed. RESULTS: AUS implantation had a 10-year mean total cost of $14 228 (SD ± 3,509) for 7.58 QALYs. AdVance sling had a mean total cost $18 938 (SD ± 12,435) for 6.43 QALYs. The incremental cost savings of AUS over 10-years was -$ 4710 with an added effectiveness of 1.15 QALYs. At a willingness to pay threshold of $50 000, AUS remained the most cost-effective option. A limitation of our analysis is the lack of direct long-term comparisons between both scenarios along with standard success definition. CONCLUSIONS: AUS implantation appears to be more economical treatment strategy for severe PPSUI compared with AdVance sling for a publicly funded health care system over a 5- and 10-year time horizon.

Changes in the outcome of prostate biopsies after preventive task force recommendation against prostate-specific antigen screening.

BACKGROUND: The benefits of PSA-based screening for prostate cancer (PCa) are controversial. The Canadian and American Task Forces on Preventive Health Care (CTFPHC & USPSTF) have released recommendations against the use of routine PSA-based screening for any men. We thought to assess the impact of these recommendations on the outcomes and trends of prostate needle biopsies. METHODS: A complete chart review was conducted for all men who received prostate needle biopsies at McGill University Health Center between 2010 and 2016. Of those, we included 1425 patients diagnosed with PCa for analysis. We Compared 2 groups of patients (pre and post recommendations' release date) using Welch's t-tests and Chi-square test. A multivariate logistic regression model was used to analyze variables predicting worse pathological outcomes. RESULTS: When the release date of the USPSTF draft (October 2011) was used as a cut-off, we found an average annual decrease of 10.6% in the total number of biopsies. The median (IQR) baseline PSA levels were higher in post-recommendations group (n = 977) when compared to pre-recommendations group (n = 448) [8 ng/ml (5.7-12.9) versus 6.4 ng/ml (4.9-10.1), respectively. P = 0.0007]. Also, post-recommendations group's patients had higher Gleason score (G7: 35.4% versus 28.4% and G8-G10: 31.2% versus 18.1%, respectively. P < 0.0001). Moreover, they had higher intermediate and high-risk PCa classification (36.4% versus 32.8% and 35.5% versus 22.1%, respectively. P < 0.0001). The recommendations release date was an independent variable associated with higher Gleason score in prostate biopsies (OR: 2.006, 95%CI: 1.477-2.725). Using the CTFPHC recommendations release date (October 2014) as a cut-off in further analysis, revealed similar results. CONCLUSIONS: Our results revealed a reduction in the number of prostate needle biopsies performed over time after the recommendations of the preventive task forces. Furthermore, it showed a significant relative increase in the higher risk PCa diagnosis. The oncological outcomes associated with this trend need to be examined in further studies.

Asporin is a stromally expressed marker associated with prostate cancer progression.

BACKGROUND: Prostate cancer shows considerable heterogeneity in disease progression and we propose that markers expressed in tumour stroma may be reliable predictors of aggressive tumour subtypes. METHODS: We have used Kaplan-Meier, univariate and multivariate analysis to correlate the expression of Asporin (ASPN) mRNA and protein with prostate cancer progression in independent cohorts. We used immunohistochemistry and H scoring to document stromal localisation of ASPN in a tissue microarray and mouse prostate cancer model, and correlated expression with reactive stroma, defined using Masson Trichrome staining. We used cell cultures of primary prostate cancer fibroblasts treated with serum-free conditioned media from prostate cancer cell lines to examine regulation of ASPN mRNA in tumour stromal cells. RESULTS: We observed increased expression of ASPN mRNA in a data set derived from benign vs tumour microdissected tissue, and a correlation with biochemical recurrence using Kaplan-Meier and Cox proportional hazard analysis. ASPN protein localised to tumour stroma and elevated expression of ASPN was correlated with decreased time to biochemical recurrence, in a cohort of 326 patients with a median follow up of 9.6 years. Univariate and multivariate analysis demonstrated that ASPN was correlated with progression, as were Gleason score, and clinical stage. Additionally, ASPN expression correlated with the presence of reactive stroma, suggesting that it may be a stromal marker expressed in response to the presence of tumour cells and particularly with aggressive tumour subtypes. We observed expression of ASPN in the stroma of tumours induced by p53 inhibition in a mouse model of prostate cancer, and correlation with neuroendocrine marker expression. Finally, we demonstrated that ASPN transcript expression in normal and cancer fibroblasts was regulated by conditioned media derived from the PC3, but not LNCaP, prostate cancer cell lines. CONCLUSIONS: Our results suggest that ASPN is a stromally expressed biomarker that correlates with disease progression, and is observed in reactive stroma. ASPN expression in stroma may be part of a stromal response to aggressive tumour subtypes.

Management of localized and advanced prostate cancer in Canada: A lifetime cost and quality-adjusted life-year analysis.

BACKGROUND: To the authors' knowledge, the literature to date lacks studies examining lifetime costs and quality-adjusted life-years (QALYs) of prostate cancer (PCa) management strategies that integrate localized and advanced disease. The objective of the current study was to assess lifetime costs and QALYs associated with contemporary PCa management strategies across risk groups by integrating localized and advanced disease. METHODS: The authors' validated Markov chain Monte Carlo model was used to predict lifetime direct costs and QALYs. The health states modeled were active surveillance, initial treatments (radical prostatectomy or radiotherapy), PCa recurrence, PCa recurrence free, metastatic castration-resistant prostate cancer, and death (cause specific/other causes). Data regarding treatment distribution, state transition probabilities, adverse effects of management options, costs, utilities, and disutilities were derived from the published literature. RESULTS: The total cost per patient for the overall cohort increased from $18,503 at 5 years to $28,032 and $39,143, respectively, at 10 years and 15 years. Furthermore, the results indicated the influence of risk group on total cost, with the high-risk group accruing the maximum per patient cost followed by the intermediate-risk and low-risk groups. Active surveillance was found to confer the most QALYs (12.5 years) and was the least costly strategy ($18,452) for individuals at low risk. For all risk groups, radical prostatectomy was less costly and conferred modestly more QALYs compared with intensity-modulated radiotherapy modalities. CONCLUSIONS: Public health care systems in Canada and elsewhere are operating under budget constraints to allocate finite resources. The findings of the current study might inform discussions concerning budget planning to provide health care services.

Predictors of costs associated with radical cystectomy for bladder cancer: A population-based retrospective cohort study in the province of Quebec, Canada.

BACKGROUND AND OBJECTIVES: There is paucity of studies on the predictors of bladder cancer (BC) management costs. We aimed to determine predictors of costs associated with radical cystectomy (RC) for BC. METHODS: We conducted a retrospective analysis in a cohort of 2,759 patients who underwent RC for BC between 2000 and 2009. We analyzed predictors of pre-surgery, RC, post-surgery, and total costs. The following variables were considered as potential predictors: age, gender, hospital/surgeon case load, academic hospital, and geo-administrative region. Multivariate linear regression was used to determine predictors. RESULTS: Predictors of pre-surgery costs were: age (ß = 808.64, P < 0.0001) and having surgery in an academic hospital (ß = 511.42, P = 0.003). Increased RC costs were associated with age (ß = 196.73, P = 0.0006), hospital/surgeon annual load (ß = 484.45 and ß = 254.21, P < 0.0001, respectively). Having surgery in academic hospitals and geographic region were significant predictors of low RC costs (ß = -1085.82 and ß = -449.31, P < 0.0001, respectively). Increasing age and the presence of post-operative complications were predictors of high post-operative costs (ß = 623.48, ß = 5781.44, P = 0.01, respectively), while hospital load was associated with low post-surgery costs (ß = -949.79, P < 0.0001). CONCLUSION: Patients' age and surgery performed by high-volume health providers were predictive factors of high RC costs. Low RC costs were associated with surgeries performed in academic hospitals.

Predictors of preoperative delays before radical cystectomy for bladder cancer in Quebec, Canada: a population-based study.

OBJECTIVES: To characterise and measure different components of preoperative delays experienced by patients with bladder cancer before radical cystectomy (RC) in the province of Quebec, Canada and to identify the predictors of long waiting times. METHODS: We conducted a retrospective cohort study using the data of patients who underwent RC for bladder cancer between 2000 and 2009 in Quebec. The cohort was obtained with the linkage of two provincial health databases: the Régie de l'assurance maladie du Québec database (data on medical services dispensed to Quebec residents), and the Fichier des évenements démographiques de l'Institut de la statistique du Québec database (demographic data on births and deaths). For the entire cohort, we determined several components of delay from first medical visit related to bladder cancer symptoms until RC. Predictors of long delays were analysed using logistic regression. RESULTS: We analysed a total of 2778 patients who met the inclusion criteria. The median urologist referral delay was 32 days. The median delays between first urologist visit and RC and between transurethral resection of bladder tumour (TURBT) to RC were 90 days and 46 days, respectively. The median overall delay was 116 days. All components of delay progressively increased from the decade of the 1990s to the decade of the 2000s. Male gender was a protective factor for several components of delay, which suggests that gender-related variations may exist in the course of care for bladder cancer (odds ratio 0.67, 95% CI 0.50-0.89 for overall delay). Patient age and gender were associated with delayed urologist referral, delayed time to TURBT, and long overall waiting time. Factors related to the health system were associated with long cystoscopy delays. CONCLUSION: Median preoperative delays among patients with bladder cancer have been increasing and remain unacceptably long. Patient's age, gender and type of hospital facility were associated with long waiting times.

Health-care services utilization and costs associated with radical cystectomy for bladder cancer: a descriptive population-based study in the province of Quebec, Canada.

BACKGROUND: Bladder cancer (BC) has the highest lifetime treatment costs per patient of all cancers. The objective of this study was to characterize the use of health-care services and costs associated with BC among patients who underwent radical cystectomy (RC) in the province of Quebec. METHODS: We conducted a descriptive study in a retrospective cohort of patients who underwent RC for BC between 2000 and 2009. Data was obtained from two health administrative databases (RAMQ and ISQ). We calculated average costs per patient and total costs in 2014 Canadian dollars for the following components of costs: 1) Pre-surgery costs (pre and post-urologist consultations, urologist consultations, cystoscopies, TURBTs, imaging procedures); 2) Costs of radical cystectomy and 3) Post-surgery costs (urologist consultations, post-operative consultations, medical oncologist consultations, imaging procedures and post-operative complication management). ARIMA models were used to evaluate trends in average costs per patient over the study period. RESULTS: Among 2759 patients included in the study (75% men), average pre-surgery costs, RC costs, and post-surgery costs were estimated at 3762$, 18979$ and 4770$, respectively. RC cost was responsible for 69% of total costs, followed by post-operative consultations (7.8%), post-operative complications and TURBTs (6% of total costs, each). Academic hospitals performed RC at a lower average cost, compared to community hospitals (difference of $1000, p < .0001). A decreased trend in post-surgery costs was detected in the year 2009. CONCLUSIONS: Costs of RC, TURBT, consultations and post-operative complications were the most important economic components of total RC cost per patient in Quebec. Academic hospitals performed RC at a lower cost, compared to community hospitals.

Contemporary cost-effectiveness analysis comparing sequential bacillus Calmette-Guerin and electromotive mitomycin versus bacillus Calmette-Guerin alone for patients with high-risk non-muscle-invasive bladder cancer.

BACKGROUND: Sequential bacillus Calmette-Guerin (BCG) and electromotive mitomycin (sequential therapy) have been shown in a randomized prospective trial to be superior to therapy with BCG alone in patients with high-risk non-muscle-invasive bladder cancer. The objective of the current study was to compare the costs and benefits of these 2 treatment strategies by performing a 5-year and 10-year cost-effectiveness study. METHODS: A Markov model was developed to estimate the incremental cost-effectiveness ratio over a 5-year and 10-year period. Estimates of disease progression, death, and treatment efficacy were obtained from what to the authors' knowledge is the only randomized trial comparing the 2 therapies. Costs included: 1) medical costs (physician fees); 2) drug costs (preparation and instillation); and 3) hospital costs (procedure fees, admission fees, and tests and procedures done during surveillance). Patients were allowed a second course of induction therapy. RESULTS: Sequential therapy was found to be associated with a higher initial material cost for induction and maintenance. The average effectiveness for the patients treated with therapy with BCG alone was 4.39 years with a mean cost of $9236 (95% confidence interval, $9118-$9345) per patient. The sequential group resulted in an average effectiveness of 4.65 years, with a mean cost of $16,468 (95% confidence interval, $16,371-$16,527). The 5-year incremental cost-effectiveness ratio of sequential versus BCG-alone therapy was $27,815 per life-year gained. The corresponding figure over a 10-year period was $8618 per life-year gained. CONCLUSIONS: The results of the current study suggest that sequential therapy is a cost-effective treatment for patients with high-risk non-muscle-invasive bladder cancer.

Drug costs in the management of metastatic castration-resistant prostate cancer in Canada.

BACKGROUND: For Canadian men, prostate cancer (PCa) is the most common cancer and the 3rd leading cause of cancer mortality. Men dying of PCa do so after failing castration. The management of metastatic castration-resistant prostate cancer (mCRPC) is complex and the associated drug treatments are increasingly costly. The objective of this study was to estimate the cost of drug treatments over the mCRPC period, in the context of the latest evidence-based approaches. METHODS: Two Markov models with Monte-Carlo microsimulations were developed in order to simulate the management of the disease and to estimate the cost of drug treatments in mCRPC, as per Quebec's public healthcare system. The models include recently approved additional lines of treatment after or before docetaxel (i.e. abiraterone and cabazitaxel). Drug exposure and survival were based on clinical trial results and clinical practice guidelines found in a literature review. All costs were assigned in 2013 Canadian dollars ($). Only direct drug costs were estimated. RESULTS: The mean cost of mCRPC drug treatments over an average period of 28.1 months was estimated at $48,428 per patient (95% Confidence Interval: $47,624 to $49,232). The mean cost increased to $104,071 (95% CI: $102,373 - $105,770) per patient when one includes abiraterone initiation prior to docetaxel therapy. Over the mCRPC period, luteinizing hormone-releasing hormone agonists (LHRHa) prescribed to maintain castrate testosterone levels accounted for 20.4% of the total medication cost, whereas denosumab prescribed to decrease bone-related events accounted for 30.5% of costs. When patients received cabazitaxel in sequence after abiraterone and docetaxel, the mCRPC medications cost per patient per month increased by 60.2%. The total cost of medications for the treatment of each annual Canadian cohort of 4,000 mCRPC patients was estimated at $ 193.6 million to $416.3 million. CONCLUSIONS: Our study estimates the direct drug costs associated with mCRPC treatments in the Canadian healthcare system. Recently identified effective yet not approved therapies will become part of the spectrum of mCRPC treatments, and may potentially increase the cost.

Secondary bladder and colorectal cancer after treatments for prostate cancer: A population based study.

BACKGROUND: Prostate cancer (PCa) patients receiving radiotherapy may be predisposed to secondary malignancies. This study aimed to determine the association between PCa treatments, including radical prostatectomy (RP), external beam radiation therapy (EBRT), brachytherapy (BT) and androgen deprivation therapy (ADT); and secondary bladder and colorectal cancer. METHODS: A cohort study was constructed using Quebec administrative databases (Med-Echo and RAMQ). Included men were diagnosed and treated for PCa between 2000 and 2016. Patients with bladder or colorectal cancer prior to PCa were excluded. Follow-up ended at the earliest of the following: incidence of bladder or colorectal cancer, death, or December 31, 2016. EBRT, BT, EBRT+ADT, RP + ADT or ADT only were compared individually to RP. The incidence of secondary bladder and colorectal cancer were computed. Inverse probability of treatment weighting (IPTW) based on a propensity score was used to control for potential confounding. IPTW-Cox proportional hazards models were used. RESULTS: A significant association was found between secondary bladder cancer and EBRT (HR: 1.84, 95%CI: 1.60;2.13), and also EBRT+ADT (HR: 2.08, 95%CI: 1.67;2.56), but not with BT (HR: 1.36, 95%CI: 0.68;2.74). Secondary colorectal cancer was significantly associated to either EBRT (HR: 1.36, 95%CI: 1.21;1.53); or BT (HR: 2.46, 95%CI: 1.71;3.54). The association between ADT alone and both secondary cancers was also significant (HR: 1.98, 95%CI: 1.69;2.31 and HR: 1.69, 95%CI: 1.49;1.92, respectively). CONCLUSIONS: Compared to PCa patients undergoing RP, the secondary bladder cancer was associated with EBRT, ADT, alone or in combination. The secondary colorectal cancer was also associated with receiving either EBRT, BT or ADT.

Benefit of Neoadjuvant Cisplatin-based Chemotherapy for Invasive Bladder Cancer Patients Treated with Radiation-based Therapy in a Real-world Setting: An Inverse Probability Treatment Weighted Analysis.

BACKGROUND: Neoadjuvant chemotherapy (NAC) improves survival for patients with muscle-invasive bladder cancer (MIBC) treated with radical cystectomy. Studies on the potential benefit of NAC before radiation-based therapy (RT) are conflicting. OBJECTIVE: To evaluate the effect of NAC on patients with MIBC treated with curative-intent RT in a real-world setting. DESIGN, SETTING, AND PARTICIPANTS: The study cohort consisted of 785 patients with MIBC (cT2-4aN0-2M0) who underwent RT at academic centers across Canada. Patients were classified into two treatment groups based on the administration of NAC before RT (NAC vs no NAC). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The inverse probability of treatment weighting (IPTW) with absolute standardized differences (ASDs) was used to balance covariates across treatment groups. The impact of NAC on complete response, overall, and cancer-specific survival (CSS) after RT in the weighted cohort was analyzed. RESULTS AND LIMITATIONS: After applying the exclusion criteria, 586 patients were included; 102 (17%) received NAC before RT. Patients in the NAC subgroup were younger (mean age 65 vs 77 yr; ASD 1.20); more likely to have Eastern Cooperative Oncology Group performance status 0-1 (87% vs 78%; ASD 0.28), lymphovascular invasion (32% vs 20%; ASD 0.27), higher cT stage (cT3-4 in 29% vs 20%; ASD 0.21), and higher cN stage (cN1-2 in 32% vs 4%; ASD 0.81); and more commonly treated with concurrent chemotherapy (79% vs 67%; ASD 0.28). After IPTW, NAC versus no NAC cohorts were well balanced (ASD <0.20) for all included covariates. NAC was significantly associated with improved CSS (hazard ratio [HR] 0.28; 95% confidence interval [CI] 0.14-0.56; p < 0.001) and overall survival (HR 0.56; 95% CI 0.38-0.84; p = 0.005). This study was limited by potential occult imbalances across treatment groups. CONCLUSIONS: If tolerated, NAC might be associated with improved survival and should be considered for eligible patients with MIBC planning to undergo bladder preservation with RT. Prospective trials are warranted. PATIENT SUMMARY: In this study, we showed that neoadjuvant chemotherapy might be associated with improved survival in patients with muscle-invasive bladder cancer who elect for curative-intent radiation-based therapy.

Real-world Assessment of Clinical Outcomes in Patients with Metastatic Renal Cell Carcinoma with or Without Sarcomatoid Features Treated with First-line Systemic Therapies.

BACKGROUND AND OBJECTIVE: Metastatic renal cell carcinoma (mRCC) patients have been reported to have better outcomes when treated with immunotherapies (IO) compared to targeted therapies (TT). This study aims to evaluate the impact of first-line systemic therapies on survival of mRCC patients with or without sarcomatoid features using real-world data. METHODS: Metastatic RCC patients of International mRCC Database Consortium (IMDC) intermediate or high risk, diagnosed from January 2011 to December 2022, treated with first-line systemic therapies, and with histological documentation of the presence or absence of sarcomatoid features in nephrectomy specimens were identified using the Canadian Kidney Cancer information system. Patients were classified by initial treatment: (1) targeted therapy (TT) used alone or (2) immunotherapy (IO)-based systemic therapies used in combination of either IO-IO or IO-TT. The inverse probability of treatment weighting using propensity scores was used to balance for covariates. Cox proportional hazard models were used to assess the impact of initial treatment received on overall survival (OS). KEY FINDINGS AND LIMITATIONS: Of the 1202 eligible patients, 791 were treated with TT and 411 with IO combinations. Of the patients, 76% were male, and the majority (91%) had a nephrectomy before systemic therapy. In nonsarcomatoid patients (639 TT and 320 IO patients), treatment with IO was associated with improved OS compared with patients treated with TT (median of 72 vs 48 mo, hazard ratio [HR] 0.63, 95% confidence interval [CI] 0.50-0.80, objective response rate [ORR] of 38.5% for IO and 23.5% for TT). In sarcomatoid patients (152 TT and 91 IO patients), treatment with IO was associated with improved OS (median of 48 vs 18 mo, HR 0.41, 95% CI 0.26-0.64, ORR of 49.5% for IO and 13.8% for TT). Similar results were observed in patients with synchronous metastatic disease only. CONCLUSIONS AND CLINICAL IMPLICATIONS: IO treatment was associated with improved survival in mRCC patients. The magnitude of benefit is increased in patients with sarcomatoid mRCC, consequently, identifying the sarcomatoid status early on could help healthcare providers make a better treatment decision. PATIENT SUMMARY: Metastatic renal cell carcinoma (mRCC) patients of International mRCC Database Consortium intermediate and high risk, diagnosed from January 2011 to December 2022, treated with first-line systemic therapies, and with histological documentation of the presence or absence of sarcomatoid features in nephrectomy specimens were identified using the Canadian Kidney Cancer information system (CKCis). In this study, treatment with immunotherapy was associated to an improved survival and response rates for mRCC patients with and without sarcomatoid features. The magnitude of benefit is increased in patients with sarcomatoid mRCC.

Adherence to antihypertensive agents improves risk reduction of end-stage renal disease.

Uncontrolled hypertension is associated with an increased risk of end-stage renal disease (ESRD). Intensified blood pressure control may slow progression of chronic kidney disease; however, the impact of antihypertensive agent adherence on the prevention of ESRD has never been evaluated. Here we assessed the impact of antihypertensive agent adherence on the risk of ESRD in 185,476 patients in the RAMQ databases age 45 to 85 and newly diagnosed/treated for hypertension between 1999 and 2007. A case cohort study design was used to assess the risk of and multivariate Cox proportional models were used to estimate the adjusted hazard ratio of ESRD. Adherence level was reported as a medication possession ratio. Mean patient age was 63 years, 42.2% male, 14.0% diabetic, 30.3% dyslipidemic, and mean follow-up was 5.1 years. A high adherence level of 80% or more to antihypertensive agent(s) compared to a lower one was related to a risk reduction of ESRD (hazard ratio 0.67; 95% confidence intervals 0.54-0.83). Sensitivity analysis revealed that the effect is mainly in those without chronic kidney disease. Risk factors for ESRD were male, diabetes, peripheral artery disease, chronic heart failure, gout, previous chronic kidney disease, and use of more than one agent. Thus, our study suggests that a better adherence to antihypertensive agents is related to a risk reduction of ESRD and this adherence needs to be improved to optimize benefits.