Aspirin and prostate cancer prevention

Aspirin’s anti-cancer effect was first reported in animals in 1972 [1]. Since then, there has been tremendous interest in aspirin, a relatively non-toxic drug, to prevent cancer. Forty years after the initial publication of aspirin’s effects on cancer, a meta-analysis from 51 randomized trials in humans demonstrated that daily aspirin use for ≥5 years significantly reduced cancer mortality, an effect that was independent of aspirin dose [2]. However, the effects of aspirin and other nonaspirin non-steroidal anti-inflammatory drugs (NSAIDs) on cancer incidence and prevention are less clear. For example, while the evidence is stronger for NSAIDs and lower risk of cancers such as melanoma, colorectal, breast and lung, the association with prostate cancer risk is inconclusive [3]. Indeed, a meta-analysis found that in European studies, NSAID use was associated with an increased risk of prostate cancer, whereas in North American studies, NSAID use was associated with lower prostate cancer risk [4]. One explanation for the disparate results is detection bias due to PSA screening given that aspirin and NSAIDs lower PSA. Indeed, in North America, where most men are screened with PSA, lower PSA induced by aspirin and NSAIDs would lead to fewer biopsies and fewer cancers detected. This may explain the lower prostate cancer risk with aspirin and NSAIDs use in North America. In contrast, in Europe, where PSA screening is less common, the effect of artificially lowered PSA is less relevant, and there is no “protective” effect of aspirin and NSAIDs use. Also, as aspirin and NSAIDs are used to treat pain, perhaps men in Europe with undiagnosed prostate cancer had pain related to their cancer necessitating aspirin/NSAID use resulting in reverse causation (i.e. the cancer led to pain necessitating aspirin/NSAID use, not the other way around). This would be moot in North America as aggressive screening results in few men presenting with pain at diagnosis. Given these issues, the true association between anti-inflammatory medications and prostate cancer risk is unclear.