IMPORTANCE - 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.
DESIGN, SETTING AND PARTICIPANTS - 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.
MAIN OUTCOME AND MEASURES - 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 AND RELEVANCE - 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.
JAMA Oncol. 2015 Jun 1;1(3):314-20. doi: 10.1001/jamaoncol.2015.0387.
Azoulay L1, Eberg M2, Benayoun S3, Pollak M4.
1 Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, Quebec, Canada2Department of Oncology, McGill University, Montreal, Quebec, Canada.
2 Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, Quebec, Canada.
3 Division of Urology, University of Montreal, Maisonneuve-Rosemont Hospital, Montreal, Quebec, Canada.
4 Department of Oncology, McGill University, Montreal, Quebec, Canada.