Statins during androgen-ablative prostate cancer therapies may offer mortality benefit
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In a systemic review and meta-analysis, statin therapy during androgen-ablative therapies was associated with a potential mortality benefit for men being treated for prostate cancer.
Heterogeneity for these results remained substantial and warrants further research in randomized clinical trials, the researchers wrote in JAMA Network Open.
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“The notion of incorporating a readily available medication with an established cardiovascular benefit and favorable toxicity profile, such as statins, in the treatment of prostate cancer is exciting. In this systematic review and meta-analysis of observational studies, we identified a significant overall mortality and prostate cancer-specific mortality advantage of concurrent statin use for men receiving androgen-ablative therapies,” Viranda H. Jayalath, MD, MSc, resident in the division of urology, department of surgery, at the University of Toronto, and colleagues wrote. “However, the use of retrospective data and unexplained heterogeneity lower our confidence in directly incorporating these findings into clinical practice. In seeking the optimal setting for statins to succeed in treating prostate cancer, work remains to delineate an optimal statin dose and class. The time is ripe for well-designed, randomized clinical trials to evaluate the effect of statins on prostate cancer survival.”
Jayalath and colleagues conducted a meta-analysis of 25 cohorts including 119,878 men to evaluate whether statin use during androgen deprivation or androgen receptor axis-targeted therapies for prostate cancer was associated with reduced overall and prostate cancer-related mortality.
Overall, 55% of the cohort was taking statin therapy and 74,416 deaths were recorded.
Researchers reported that statin use while undergoing androgen-ablative therapy for prostate cancer was associated with a 27% lower risk for overall mortality (HR = 0.73; 95% CI, 0.66-0.82; I2 = 83%) and a 35% lower risk for prostate cancer-related mortality (HR = 0.65; 95% CI, 0.58-0.73; I2 = 74%). Heterogeneity for both outcomes was high.
The results of a subgroup analysis indicated an advantage associated with statin therapy during androgen receptor axis-targeted therapies compared with androgen deprivation therapy alone (HR for androgen receptor axis-targeted therapies = 0.4; 95% CI, 0.3-0.55; vs. HR for androgen deprivation therapy alone = 0.68; 95% CI, 0.6-0.76; P for difference = .002). Confidence in the evidence was rated low, according to the researchers.
“It is particularly noteworthy that serum cholesterol levels were not adjusted for in any included studies. Serum cholesterol levels appear to correlate with levels of prostate-specific antigen and may in part drive the statin-prostate cancer association, potentially contributing to residual confounding of these findings,” the researchers wrote. “There remained unexplained interstudy heterogeneity in both primary outcomes. It is worth noting, however, that although variability remained considerable, the differences were between small and large protective associations; in other words, these findings appear to accurately support a statin benefit, although they may be restricted by imprecision.”
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