Statin Use During Prostate Cancer ADT Ups Survival

STATIN USE during androgen-ablative therapies may improve survival among men with advanced prostate cancer.

In a systematic review and metaanalysis of 25 cohorts including 119,878 men, concurrent statin use was significantly associated with a 27% reduced risk of all-cause mortality and a 35% reduced risk of prostate cancerspecific mortality, Robert J. Hamilton, MD, MPH, of the University of Toronto in Canada, and colleagues reported in JAMA Network Open. Overall, 65,488 men (55%) were taking statins.

In subgroup analyses, men receiving androgen-receptor axis targeted therapy (ie, abiraterone or enzalutamide) had a significantly greater reduction in prostate cancer mortality risk with concurrent statin use compared with men taking androgen deprivation therapy (ADT) alone: 60% vs 32% reduced risk.

“We observed a consistent overall and prostate cancer-specific survival advantage for statin users undergoing androgen-ablative therapies, independent of patient age, baseline metastasis status, prior use of chemotherapy, or primary treatment type,” Dr Hamilton’s team explained. “For overall mortality, the observed benefit was independent of hormone sensitivity status and type of androgen-ablative therapy.”

The investigators acknowledged substantial heterogeneity among studies and a low confidence in the evidence according to the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach.

With respect to plausible mechanisms of action, the investigators noted that statins may inhibit inflammation, angiogenesis, cell proliferation, migration, adhesion, and invasion and promote apoptosis. Statins may also work synergistically with androgen-ablative therapies to lower circulating and intraprostatic androgen precursors.

Given the limitations of observational research, Dr Hamilton’s team encouraged randomized clinical trials to evaluate the effect of statins on prostate cancer survival and to determine the optimal statin class and dose. ■ risk for ESKD, a 20% decreased risk of a decline in eGFR to less than 15 mL/ min/1.73 m2, and 17% decreased risk of a greater than 40% decline in eGFR.

In addition, the risk of cardiovascular composite endpoints significantly