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. 2022 Jul 1;8(7):1019-1026.
doi: 10.1001/jamaoncol.2022.1501.

Association of 5α-Reductase Inhibitors With Prostate Cancer Mortality

Lars Björnebo  1 , Tobias Nordström  1   2 , Andrea Discacciati  1 , Thorgerdur Palsdottir  1 , Markus Aly  3 , Henrik Grönberg  1 , Martin Eklund  1 , Anna Lantz  1   3
Affiliations

Association of 5α-Reductase Inhibitors With Prostate Cancer Mortality

Lars Björnebo et al. JAMA Oncol. .

Erratum in

  • Errors in Author Affiliations and Figure 2.
    [No authors listed] [No authors listed] JAMA Oncol. 2022 Jun 16:e222696. doi: 10.1001/jamaoncol.2022.2696. Online ahead of print. JAMA Oncol. 2022. PMID: 35708718 Free PMC article. No abstract available.
  • Error in Figure 2.
    [No authors listed] [No authors listed] JAMA Oncol. 2022 Oct 1;8(10):1518. doi: 10.1001/jamaoncol.2022.3737. JAMA Oncol. 2022. PMID: 35980650 Free PMC article. No abstract available.

Abstract

Importance: There is evidence that 5α-reductase inhibitors (5-ARIs), a standard treatment of benign prostate hyperplasia, are associated with a decrease in the incidence of prostate cancer (PCa). However, studies to date have had conflicting results regarding the association with prostate cancer mortality (PCM).

Objective: To evaluate the association of treatment with 5-ARIs with PCM in men without a prior diagnosis of PCa.

Design, setting, and participants: This population-based cohort study was conducted in Stockholm, Sweden, between January 1, 2007, and December 31, 2018, and included 429 977 men with a prostate-specific antigen (PSA) test within the study period. Study entry was set to 1 year after the first PSA test. Data were analyzed from September 2021 to December 2021.

Exposures: After their initial PSA test, men with 2 or more newly dispensed prescriptions of 5-ARI, finasteride, or dutasteride were considered 5-ARI users (n = 26 190).

Main outcomes and measures: Primary outcome was PCM. Cox proportional hazards regression models were used to calculate multivariable-adjusted hazard ratios (HRs) and 95% CIs for all-cause mortality and PCM.

Results: The study cohort included 349 152 men. The median (IQR) age for those with 2 or more filled prescriptions of 5-ARI was 66 (61-73) years and 57 (50-64) years for those without. The median follow-up time was 8.2 (IQR, 4.9-10) years with 2 257 619 person-years for the unexposed group and 124 008 person-years for the exposed group. The median exposure to treatment with 5-ARI was 4.5 (IQR, 2.1-7.4) years. During follow-up, 35 767 men (8.3%) died, with 852 deaths associated with PCa. The adjusted multivariable survival analysis showed a lower risk of PCM in the 5-ARI group with longer exposure times (0.1-2.0 years: adjusted HR, 0.89; 95% CI, 0.64-1.25; >8 years: adjusted HR, 0.44; 95% CI, 0.27-0.74). No statistically significant differences were seen in all-cause mortality between the exposed and unexposed group. Men treated with 5-ARIs underwent more PSA tests and biopsies per year than the unexposed group (median of 0.63 vs 0.33 and 0.22 vs 0.12, respectively).

Conclusions and relevance: The results of this cohort study suggest that there was no association between treatment with 5-ARI and increased PCM in a large population-based cohort of men without a previous PCa diagnosis. Additionally, a time-dependent association was seen with decreased risk of PCM with longer 5-ARI treatment. Further research is needed to determine whether the differences are because of intrinsic drug effects or PCa testing differences.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Nordström reported personal fees from Ipsen and owning stock in A3P Biomedical AB outside the submitted work. Dr Grönberg reported grants from Janssen and personal fees from Bayer, Astella, and AstraZeneca as well as owning stock and holding patents in A3P Biomedical AB outside the submitted work. Dr Eklund reported grants from the Swedish Research Council, Swedish Cancer Society, and Swedish Prostate Cancer Society during the conduct of the study as well as owning stock and holding patents in A3P Biomedical AB outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Flowchart of Men Included in the Study Cohort
5-ARI indicates 5α-reductase inhibitor; PSA, prostate-specific antigen; TURP, transurethral resection of the prostate. aThese categories are not mutually exclusive.
Figure 2.
Figure 2.. All-Cause and Prostate Cancer Survival Probabilities in Men Exposed and Unexposed to 5α-Reductase Inhibitors (5-ARIs) at Study Start
Adjusted for age, prostate-specific antigen levels, previous negative biopsy, family history of prostate cancer, education, civil status, Charlson Comorbidity Index scores, and year of study entry. Solid lines indicate adjusted survival probabilities; dashed lines, 95% pointwise CIs.
See this image and copyright information in PMC

Comment in

  • Benign Prostatic Hyperplasia.
    Kaplan SA. Kaplan SA. J Urol. 2022 Nov;208(5):1135-1137. doi: 10.1097/JU.0000000000002907. Epub 2022 Aug 11. J Urol. 2022. PMID: 35950379 No abstract available.

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