Statin use and survival in men receiving androgen-ablative therapies for advanced prostate cancer: A systematic review and meta-analysis of cohort studies
Viranda Jayalath1, Roderick Clark1, Katherine Lajkosz1, Neil E. Fleshner1,2, Laurence Klotz1,3, Robert J. Hamilton1,2.
1Division of Urology, Department of Surgery, University of Toronto, Toronto, ON, Canada; 2Division of Urology, Department of Surgery, University Health Network, Toronto, ON, Canada; 3Division of Urology, Department of Surgery, Sunnybrook Hospital, Toronto, ON, Canada
Introduction: Evidence supports a role for statins in improving survival in advanced prostate cancer (PCa), particularly among men on androgen-ablative therapies. We systemically reviewed and meta-analyzed the relationship between statin use and survival among men with PCa on androgen deprivation therapy (ADT) or androgen receptor-axis-targeted therapies (ARATs).
Methods: Six databases were searched from inception to May 18, 2021, for studies reporting on post-diagnostic statin use and survival outcomes (hazard ratios [HRs]). Two authors independently abstracted all data. Study quality was assessed using the Newcastle-Ottawa Scale. The primary outcomes included overall mortality (OM) and prostate cancer-specific mortality (PCSM). Summary estimates pooled multivariable HRs with 95% confidence intervals (CIs) using the generic inverse variance method with random-effects modeling. Heterogeneity was assessed and quantified. A priori subgroup and sensitivity analyses were undertaken, and publication bias was evaluated. Confidence in the evidence was assessed using GRADE.
Results: Twenty-five cohorts of 119 878 men (64 717 statin users [54%]) with over 74 416 mortality events were included. Post-diagnostic statin use was associated with a 27% reduction in the risk of OM (19 cohorts, HR 0.73, 95% CI 0.66–0.82, I2=83%) and a 35% reduction in the risk of PCSM (14 cohorts, HR 0.65, 95% CI 0.58–0.73, I2=74%), with significant heterogeneity in both estimates. Subgroup analyses identified a PCSM advantage of statins for men on ARATs compared to ADT (HR 0.40, 95%CI 0.30–0.55 vs. HR 0.68, 95% CI 0.60–0.76, p-difference <0.01). Confidence in the overall evidence was “low” for both outcomes.
Conclusions: Post-diagnostic statin use reduced both overall and prostate cancer-specific mortality in men on androgen-ablative therapies for advanced PCa. Randomized controlled trials are warranted to validate these findings.
