Statin use during androgen-ablative therapies may improve survival among men with advanced prostate cancer, a new study suggests.
In a systematic review and meta-analysis 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 cancer-specific 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, the investigators reported.
“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.
“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,” according to the investigators.
Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
Jayalath VH, Clark R, Lajkosz K, et al. Statin use and survival among men receiving androgen-ablative therapies for advanced prostate cancer: a systematic review and meta-analysis. JAMA Netw Open. Published online November 30, 2022. doi:10.1001/jamanetworkopen.2022.42676