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. 2024 Aug 1;7(8):e2430223.
doi: 10.1001/jamanetworkopen.2024.30223.

5-α Reductase Inhibitors and Prostate Cancer Mortality

Robert J Hamilton  1   2 , Julian Chavarriaga  1 , Najia Khurram  1 , Cindy Lau  3 , Jin Luo  3 , Ning Liu  3 , Maria Komisarenko  1 , Girish Kulkarni  1 , Christopher Wallis  1 , David N Juurlink  3 , Neil Fleshner  1 , Antonio Finelli  1
Affiliations

5-α Reductase Inhibitors and Prostate Cancer Mortality

Robert J Hamilton et al. JAMA Netw Open. .

Abstract

Importance: 5-alpha-reductase-inhibitors (5-ARIs) are approved for treating benign prostatic hyperplasia (BPH) and have been found to reduce prostate cancer (PCa) risk by 25%. However, trials also have shown 5-ARIs to be associated with high-grade PCa. Whether 5-ARIs increase mortality among those with a diagnosis of PCa remains unclear.

Objective: To determine long-term outcomes of clinically localized PCa arising in individuals taking 5-ARIs compared with nonusers.

Design, setting, and participants: This population-based cohort study was conducted between January 2003 and October 2017. Eligible participants were men aged 65 years or older in Ontario, Canada, who developed clinically localized PCa with complete pathological abstraction from the Ontario Health Administrative Databases. Data analysis occurred from November 2017 to November 2022.

Exposure: 5-ARIs before PCa diagnosis.

Main outcomes and measures: The primary outcomes were overall mortality and PCa-specific mortality. Cause-specific hazard models with inverse probability treatment weights (IPTW) were used to examine associations of 5-ARI use with mortality outcomes. Sensitivity analyses based on prediagnostic 5-ARI use, Gleason score, comorbidity, 5-ARI indication, prostate-specific antigen modeling, and statin use were also performed.

Results: The cohort included 19 938 patients with PCa. Of these, 2112 (10.6%; median [IQR] age, 74 [70-79] years) were 5-ARI users and 17 826 (89.4%; median [IQR] age, 71 [68-76] years) were nonusers. During a median (IQR) follow-up of 8.96 (6.28-12.17) years, 6053 (30.4%) died, including 1047 (5.3%) from PCa. 5-ARI use appeared to be associated with increased overall and PCa specific mortality in crude analyses; however, after IPTW, 5-ARI use was not associated with overall mortality (hazard ratio, 0.98; 95% CI, 0.90-1.07; P = .77) or PCa-specific mortality (hazard ratio, 1.02; 95% CI, 0.83-1.25; P = .84).

Conclusions and relevance: In this population-based cohort study of 5-ARI use prior to PCa diagnosis including long-term follow-up and clinicopathologic details, prediagnostic 5-ARI use was not associated with PCa-specific or all-cause mortality. This study offers reassuring safety data for patients using 5-ARIs before PCa diagnosis for both BPH and chemopreventive reasons.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Liu reported being a full-time employee of Institute for Clinical Evaluative Sciences (ICES). Dr Kulkarni reported receiving grants from Johnson and Johnson; personal fees from Ferring, Johnson and Johnson, Abbvie, Tolmar, Bristol Meyers Squibb, EMD Serono, Merck Sharp & Dohme, enGene, TerSera, Theralase, Astra Zeneca, Pfizer, Knight Pharmaceuticals, Photocure, Astellas, Novartis, and Bayer outside the submitted work. Dr Fleshner reported receiving personal fees from Janssen, Amgen, Sanofi, Astellas, Bayer, Abbvie, and Ferring; serving as Chief Marketing Officer for Verity and Point; and having worked as a consultant or received funding from Janssen, Sanofi, Astellas, Nucleix, Bayer, Progenix, Abbvie, Ferring, and Amgen outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Study Flow Diagram
5-ARI indicates 5-α reductase inhibitor; ADG indicates aggregated diagnosis group; ICD-O-3, International Classification of Diseases for Oncology (Third Edition); IKN, Institute for Clinical Evaluative Sciences (ICES) key number; PSA, prostate-specific antigen.
Figure 2.
Figure 2.. Overall Survival Comparing Those With and Without Prior 5-α Reductase Inhibitor (5-ARI) Use
Kaplan-Meier curve with inverse probability of treatment weighting.
Figure 3.
Figure 3.. Prostate Cancer–Specific Mortality Comparing Those With and Without Prior 5-α Reductase Inhibitor (5-ARI) Use
Kaplan-Meier curve with inverse probability of treatment weighting.
Figure 4.
Figure 4.. Subgroup Analysis Comparing 5-α Reductase Inhibitor (5-ARI) Use Prior to Prostate Cancer Diagnosis
5-ARI, 5-α reductase inhibitor; ADG indicates aggregated diagnosis group; BPH, benign prostatic hyperplasia; PSA, prostate-specific antigen.
See this image and copyright information in PMC

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