A new study published in JAMA Network Open has revealed that statin use may be linked to improved survival in men with advanced prostate cancer receiving apalutamide treatment. The analysis pooled individual patient data from two large, phase 3 randomized clinical trials, SPARTAN and TITAN, encompassing over 2,100 men with metastatic or nonmetastatic advanced prostate cancer. Researchers found that patients exposed to statins during their treatment had a significantly lower risk of death compared to those who did not take the cholesterol-lowering drugs.

The investigators used rigorous statistical methods, including multivariable Cox regression and inverse probability treatment weighting, to adjust for potential confounding factors such as age, body mass index, cancer stage, and cardiovascular history. Statin users in the apalutamide-treated group showed a 42% reduction in the hazard of death, with three-year overall survival rates exceeding 80%, significantly higher than their non-statin counterparts. This survival benefit was not observed consistently among patients who received placebo instead of apalutamide.

Despite these promising findings, the study also highlighted a higher incidence of serious cardiac events in patients on statins, likely reflecting the preexisting cardiovascular conditions common among these patients. The authors caution that this association may not indicate a causal relationship but rather underlying health issues that led to statin prescriptions in the first place.

Experts point to several plausible biological mechanisms through which statins could impact prostate cancer progression. Statins inhibit cholesterol synthesis, which may interfere with cancer cell signaling pathways driven by androgen receptors, potentially suppressing tumor growth. Beyond cholesterol-lowering, statins may also modulate inflammation, angiogenesis, and cell proliferation, mechanisms that could complement androgen blockade therapies like apalutamide.

However, this study’s retrospective design within clinical trials means the findings should be interpreted as hypothesis-generating. Residual confounding, lack of information on statin dose and duration, and potential drug interactions mean definitive conclusions cannot yet be drawn. The authors stress the need for prospective studies specifically designed to evaluate the role of statins in prostate cancer treatment.

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