Regular aspirin use and the risk of lethal prostate cancer in the Physicians' Health Study.

306 Background: Aspirin exerts chemopreventive effects against several malignancies. An inverse association between regular aspirin intake and advanced prostate cancer is suggested by previous reports, but potential effects on lethal prostate cancer have not been characterized. Methods: The study population comprised 22,071 male physicians enrolled in the prospective Physicians' Health Study followed from 1982-2009. We evaluated the relationship between regular aspirin intake ( > 3 tablets per week) and lethal prostate cancer (metastases or prostate cancer death). Secondary outcomes included the incidence of total, high-grade (Gleason 8-10), and advanced (T3b-T4 or N1 or M1) cancers. Cox proportional hazards models estimated age- and multivariate-adjusted hazard ratios (HR) for the incidence of primary and secondary outcomes and survival among participants with prostate cancer. Results: Over 27 years of follow-up (533,261 person-years), 3,183 men were diagnosed with prostate cancer, of whom 402 developed lethal disease. Decreased multivariate-adjusted risks of lethal prostate cancer were observed for regular aspirin users (HR: 0.67, 95%CI: 0.55-0.82). Recent regular use (within 12 months) was protective, with effects diminishing with time since last regular use (p for trend = 0.007). Among men with prostate cancer, regular aspirin use after diagnosis was associated with decreased prostate cancer mortality (HR: 0.79, 95%CI: 0.64-0.98), whereas pre-diagnostic use did not confer a measurable benefit. Regular aspirin use was not significantly associated with the incidence of total, high-grade, or advanced cancers. Conclusions: Regular aspirin use was associated with a decreased risk of lethal prostate cancer in this cohort of American physicians. An inhibitory effect of regular aspirin use on prostate cancer progression is suggested.