Aspirin Use and Lethal Prostate Cancer in the Health Professionals Follow-up Study

Background: Aspirin use probably protects against some malignancies but its effects on lethal prostate cancer (PC) are unclear. Objective: To investigate the association between regular aspirin use and lethal PC. Design, setting, and participants: Participants were aged 40-75 yr at baseline in 1986 and have been followed with biennial questionnaires. The risk analysis includes 49 409 men. The survival analysis includes 5980 PC patients without metastatic disease at diagnosis. Outcome measurements and statistical analysis: We used Cox proportional hazards regression to examine the association between current, past, or never regular aspirin use (>= 2 d/wk) in relation to lethal (metastatic or fatal) PC. We also examined years of use among current users and years since stopping among past users. In the risk analysis, aspirin was updated throughout follow-up. In the survival analysis, aspirin use after diagnosis was assessed. Results and limitations: Some 29% of participants used aspirin regularly at baseline, which increased to 60% by 2010. In the risk analysis, 804 men were diagnosed with lethal PC. Current regular aspirin was associated with a lower risk of lethal prostate cancer (hazard ratio [HR] 0.80, 95% confidence interval [CI] 0.66-0.96) compared to never users. In the survival analysis, 451 of the men diagnosed with nonmetastatic PC later developed lethal disease. Current postdiagnostic aspirin was associated with a lower risk of lethal PC (HR 0.80, 95% CI 0.64-1.00) and overall mortality (HR 0.79, 95% CI 0.69-0.90). When restricted to highly screened men, the risk analysis associations were stronger and survival analysis associations remained statistically significant. Reverse causation and residual confounding remain concerns, as demonstrated by the attenuated results in sensitivity analyses. Conclusions: Regular aspirin use was associated with a lower risk of lethal PC. Postdiagnostic use was associated with better survival after diagnosis. Patient summary: We found that it may be advisable for prostate cancer patients to take aspirin to improve their survival for both prostate cancer mortality and other mortality outcomes.