title: 5α-Reductase Inhibitors and the Risk of Cancer-Related Mortality in Men With Prostate Cancer.
abstract: OBJECTIVE
  5α-Reductase inhibitors (5-ARIs) are widely used in the treatment of benign prostatic hyperplasia. However, randomized clinical trials have raised concerns that their use may be associated with an increased risk of high-grade prostate cancer tumors that would ultimately lead to worse prostate cancer outcomes. To date, few observational studies have addressed this important safety concern.
  
  
  OBJECTIVE
  To determine whether the use of 5-ARIs before prostate cancer diagnosis is associated with an increased risk of cancer-specific and all-cause mortality in men with a new diagnosis of prostate cancer in the real-world setting.
  
  
  METHODS
  A retrospective cohort study was conducted in a cohort of 13,892 men with a new diagnosis of prostate cancer between January 1, 1999, and December 31, 2009, who were followed up until October 1, 2012. Patients were individually linked across 4 databases from the United Kingdom: National Cancer Data Repository, Clinical Practice Research Datalink, Hospital Episodes Statistics database, and Office for National Statistics database.
  
  
  METHODS
  Cox proportional hazards models were used to estimate hazard ratios (HRs) with 95% CIs of prostate cancer-specific and all-cause mortality associated with prediagnostic use of 5-ARIs. For each outcome, 2 models were constructed, one adjusted for predefined covariates (conventional model) and another adjusted for high-dimensional propensity score (HD-PS) deciles.
  
  
  RESULTS
  During a mean (SD) of 4.5 (3.1) years, 5001 deaths occurred, including 2429 from prostate cancer (crude incidence rate of 3.86 per 100 person-years [95% CI, 3.71-4.02]). In the conventional model, use of 5-ARIs before prostate cancer diagnosis was not associated with an increased risk of prostate cancer-specific mortality (crude incidence rates, 3.76 [95% CI, 3.04-4.59] [use] vs 3.87 [95% CI, 3.71-4.03] [nonuse] per 100 person-years; adjusted hazard ratio [aHR], 0.86 [95% CI, 0.69-1.06]) and all-cause mortality (crude incidence rates, 8.42 [95% CI, 7.32-9.64] [use] vs 7.93 [95% CI, 7.71-8.16] [nonuse] per 100 person-years; aHR, 0.87; 95% CI, 0.75-1.00). Similar results were observed with the HD-PS adjusted model (prostate cancer-specific mortality: aHR, 0.90 [95% CI, 0.73-1.13]; and all-cause mortality: aHR, 0.92 [95% CI, 0.80-1.07]).
  
  
  CONCLUSIONS
  The use of 5-ARIs was not associated with an increased risk of prostate cancer-specific and all-cause mortality in men with a new diagnosis of prostate cancer. While these results provide reassurance, additional studies are needed to replicate these findings.
authors.affiliation: Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, Quebec, Canada2Department of Oncology, McGill University, Montreal, Quebec, Canada.
authors.forename: Laurent
authors.initials: L
authors.lastname: Azoulay
authors.affiliation: Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, Quebec, Canada.
authors.forename: Maria
authors.initials: M
authors.lastname: Eberg
authors.affiliation: Division of Urology, University of Montreal, Maisonneuve-Rosemont Hospital, Montreal, Quebec, Canada.
authors.forename: Serge
authors.initials: S
authors.lastname: Benayoun
authors.affiliation: Department of Oncology, McGill University, Montreal, Quebec, Canada.
authors.forename: Michael
authors.initials: M
authors.lastname: Pollak
mesh_terms: D058891:5-alpha Reductase Inhibitors / Q000009:adverse effects*; D016208:Databases, Factual; D000068538:Dutasteride / Q000009:adverse effects*; D018120:Finasteride / Q000009:adverse effects*; D006801:Humans; D015994:Incidence; D053208:Kaplan-Meier Estimate; D016014:Linear Models; D016015:Logistic Models; D008297:Male; D015999:Multivariate Analysis; D057216:Propensity Score; D016016:Proportional Hazards Models; D011470:Prostatic Hyperplasia / Q000175:diagnosis / Q000188:drug therapy*; D011471:Prostatic Neoplasms / Q000139:chemically induced* / Q000175:diagnosis / Q000401:mortality*; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D006113:United Kingdom / Q000453:epidemiology
chemical_list: D058891:5-alpha Reductase Inhibitors; D018120:Finasteride; D000068538:Dutasteride