Statins and prostate cancer—hype or hope? The epidemiological perspective

BACKGROUND: Men using cholesterol-lowering statin medications have been found to have lower risks of both advanced and fatal prostate cancer in multiple registry-based studies and prospective cohort studies. Statin use has also been associated with longer survival among men already diagnosed with prostate cancer. Mechanisms responsible for purported anti-cancer effects of statins are not well understood but may offer insight into prostate cancer biology. METHODS: We summarise epidemiological data from studies of statins and prostate cancer and discuss to what extent these findings can be interpreted as causal. Additionally, lipid-mediated and non-lipid-mediated mechanisms that may contribute to potential anti-cancer effects of statins are reviewed. Finally, we consider treatment settings and molecular subgroups of men who might benefit more than others from statin use in terms of prostate cancer-specific outcomes. RESULTS: Data from prospective observational studies generally reported a lower risk of fatal prostate cancer among statin users. There is some evidence for serum cholesterol-lowering as an indirect mechanism linking statins with advanced and fatal prostate cancer. Window-of-opportunity clinical trials show measurable levels of statins in prostate tissue highlighting potential for direct effects, whilst observational data suggest possible statin-driven modulation of prostate microenvironment inflammation. Additionally, emerging data from registry studies support a potential role for statins within the context of androgen deprivation therapy and anti-androgen treatment. CONCLUSION: Prospective and registry-based studies support a lower risk of advanced and fatal prostate cancer in statin users relative to non-users, as well as better outcomes among prostate cancer patients. The few randomised-controlled trials conducted so far have short follow-up, lack identified molecular subgroups, and do not provide additional support for the observational results. Consequently, additional evidence is required to determine which men may experience greatest benefit in terms of prostate cancer-specific outcomes and how statin effects may vary according to molecular tumour characteristics.