In a Swedish study reported in JAMA Oncology, Björnebo et al found that longer use of 5α-reductase inhibitors (5-ARIs) for the treatment of benign prostatic hyperplasia was associated with a reduced risk of prostate cancer mortality among men without a prior diagnosis of prostate cancer.
As stated by the investigators, “There is evidence that 5-ARIs, a standard treatment of benign [prostatic] hyperplasia, are associated with a decrease in the incidence of prostate cancer. However, studies to date have had conflicting results regarding the association with prostate cancer mortality.”
Study Details
The study included 349,152 men aged ≥ 40 years from the Stockholm PSA and Biopsy Register who underwent prostate-specific antigen (PSA) testing between January 2007 and December 2017. Study entry was set to 1 year after the first PSA test. A total of 26,190 men with at least two newly dispensed prescriptions of a 5-ARI (finasteride or dutasteride) after initial PSA testing were considered 5-ARI users.
Key Findings
Median age was 66 years for 5-ARI users and 57 years for nonusers. 5-ARI users were more likely to have had a previous negative biopsy, higher PSA levels, and higher Charlson Comorbidity Index scores.
Median follow-up was 8.2 years (interquartile range [IQR] = 4.9–10 years). Among 5-ARI users, median exposure to treatment was 4.5 years (IQR = 2.1–7.4 years).
Prostate cancer was diagnosed in 1,377 5-ARI users (0.4%) and 14,804 nonusers (4.2%). A total of 35,767 men (8.3%) died, with 852 deaths attributed to prostate cancer.
In multivariate analysis adjusted for age, PSA level, previous negative biopsy, family history of prostate cancer, education, civil status, Charlson Comorbidity Index score, and year of study entry, adjusted hazard ratios (HRs) for prostate cancer mortality compared with 0 years of exposure to 5-ARIs were 0.89 (95% confidence interval [CI] = 0.64–1.25) for 0.1 to 2.0 years, 0.54 (95% CI = 0.37–0.78) for 2 to 4 years, 0.72 (95% CI = 0.52–1.01) for 4 to 6 years, 0.51 (95% CI = 0.33–0.79) for 6 to 8 years, and 0.44 (95% CI = 0.27–0.74) for longer than 8 years.
In adjusted analysis, no significant differences in all-cause mortality were observed between 5-ARI users and nonusers, with hazard ratios ranging from 0.97 (> 8 years) to 1.04 (4–6 years) across years of exposure to 5-ARIs. 5-ARI users underwent more PSA tests (median = 0.63 vs 0.33 per year) and biopsies (median = 0.22 vs 0.12 per year) vs nonusers.
The investigators concluded, “The results of this cohort study suggest that there was no association between treatment with 5-ARIs and increased prostate cancer mortality in a large population-based cohort of men without a previous prostate cancer diagnosis. Additionally, a time-dependent association was seen with decreased risk of prostate cancer mortality with longer 5-ARI treatment. Further research is needed to determine whether the differences are because of intrinsic drug effects or prostate cancer testing differences.”
Lars Björnebo, MD, MSc, of the Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Solna, is the corresponding author for the JAMA Oncology article.
Disclosure: The study was supported by the Stockholm County Council and the Åke Wiberg Foundation. For full disclosures of the study authors, visit jamanetwork.com.
