Prostate Cancer Incidence and Mortality in Men Exposed to α1-Adrenoceptor Antagonists.

BACKGROUND: α1-antagonists are commonly used to treat benign prostatic hyperplasia. Preclinical studies suggest they induce cell death and inhibit tumor growth. This study evaluates the risk of prostate cancer death in men using α1-antagonists.

METHODS: A population-based cohort study in Stockholm, Sweden (January 1, 2007 to December 31, 2019) including 451,779 men with a prostate-specific antigen (PSA) test. Study entry was one year after the first PSA test. Men were considered exposed at their second filled prescription. Primary outcome: prostate cancer mortality. Secondary outcomes: all-cause mortality and prostate cancer incidence. Cox proportional hazard regression models were used to calculate adjusted hazard ratios (HRs) and 95% CIs for all outcomes. Inverse probability weighting with marginal structural models accounted for time-dependent confounders.

RESULTS: Of 351,297 men in the cohort, 39,856 (11.3%) were exposed to α1-antagonists. Median follow-up for prostate cancer mortality was 8.9 years and median exposure time to α1-antagonists was 4.4 years. There was no evidence of an association between α1-antagonist use and prostate cancer mortality, all-cause mortality, or high-grade prostate cancer. α1-antagonist-use was associated with an increased risk of prostate cancer (HR: 1.11, 95% CI: 1.06-1.17) and low-grade prostate cancer (HR: 1.22, 95% CI: 1.11-1.33). Men treated with α1-antagonists had more frequent PSA testing.

CONCLUSIONS: Our findings show no significant association between α1-adrenoceptor antagonist exposure and prostate cancer mortality or high-grade prostate cancer. Although the preclinical evidence indicates a potential chemopreventive effect, this study's findings do not support it.