Statin Use and Survival Among Men Receiving Androgen-Ablative Therapies for Advanced Prostate Cancer: A Systematic Review and Meta-analysis

Abstract

Importance: Epidemiological evidence supports a role for statins in improving survival in advanced prostate cancer, particularly among men receiving androgen-ablative therapies.

Objective: To study the association between statin use and survival among men with prostate cancer receiving androgen deprivation therapy (ADT) or androgen receptor axis-targeted therapies (ARATs).

Data sources: This systemic review and meta-analysis used sources from MEDLINE, EMBASE, Epub Ahead of Print, Cochrane Clinical Trials, Cochrane Systematic Reviews, and Web of Science from inception to September 6, 2022.

Study selection: Observational studies reporting associations of concurrent statin use and survival outcomes (in hazard ratios [HRs]).

Data extraction and synthesis: Two authors independently abstracted all data. Summary estimates pooled multivariable HRs with 95% CIs using the generic inverse variance method with random-effects modeling. A priori specified subgroup and sensitivity analyses were undertaken, and heterogeneity, study quality, and publication bias were evaluated. Confidence in the evidence was assessed using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach.

Main outcomes and measures: Overall mortality and prostate cancer-specific mortality (PCSM).

Results: Twenty-five cohorts of 119 878 men (65 488 statin users [55%]) with more than 74 416 deaths were included. Concurrent statin use was associated with a 27% reduction in the risk of overall mortality (HR, 0.73 [95% CI, 0.66-0.82]; I2 = 83%) and a 35% reduction in the risk of PCSM (HR, 0.65 [95% CI, 0.58-0.73]; I2 = 74%), with substantial heterogeneity in both estimates. Subgroup analyses identified a PCSM advantage associated with statins for men receiving ARATs compared with ADT alone (HR, 0.40 [95% CI, 0.30-0.55] vs 0.68 [95% CI, 0.60-0.76]; P = .002 for difference). Confidence in the evidence was rated low for both outcomes.

Conclusions and relevance: The findings of this meta-analysis show that concurrent statin use was associated with reduced overall mortality and PCSM among men receiving androgen-ablative therapies for advanced prostate cancer. These findings are limited by the observational nature of the data and residual unexplained interstudy heterogeneity. Randomized clinical trials are warranted to validate these results.

Figure 1.. Forest Plot of the Association Between Postdiagnostic Statin Use and Overall Mortality Among Men Receiving Androgen-Ablative Therapies for Advanced Prostate Cancer

Includes 19 cohorts and 108 512 men. The diamond represents the pooled estimate, derived from generic inverse variance (IV) random-effects modeling. Each square represents individual study estimates; the size of each square corresponds to the weight attributed to each cohort in the overall summary estimate. The horizontal lines represent 95% CIs. Interstudy heterogeneity was assessed using the Cochran Q statistic and quantified with the I² statistic (>50% is considered substantial). ^aData available only in the form of an abstract. ^bOwing to rounding, individual values sum to greater than 100%.

Figure 2.. A Priori Subgroup Analyses Evaluating the Association Between Postdiagnostic Statin Use and Risk of Overall Mortality Among Men Receiving Androgen-Ablative Therapies for Advanced Prostate Cancer

Includes 19 cohorts and 108 512 men. The diamond represents the pooled estimate, derived from generic inverse variance random-effects modeling. Each square represents the respective subgroup pooled estimate. The horizontal lines represent 95% CIs. Interstudy heterogeneity was assessed using the Cochran Q statistic and quantified with the I² statistic (>50% is considered substantial). ADT indicates androgen deprivation therapy; ARAT, androgen receptor axis–targeted therapy; CRPC, castration-resistant prostate cancer; CV, cardiovascular; HR, hazard ratio; HSPC, hormone-sensitive prostate cancer.

Figure 3.. Forest Plot of the Association Between Postdiagnostic Statin Use and Prostate Cancer–Specific Mortality Among Men Receiving Androgen-Ablative Therapies for Advanced Prostate Cancer

Includes 14 cohorts and 115 612 men. The diamond represents the pooled estimate, derived from generic inverse variance (IV) random-effects modeling. Each square represents individual study estimates; the size of each square corresponds to the weight attributed to each cohort in the overall summary estimate. The horizontal lines represent 95% CIs. Interstudy heterogeneity was assessed using the Cochran Q statistic and quantified with the I² statistic (>50% is considered substantial). ADT indicates androgen deprivation therapy; RT, radiation therapy. ^aData available only in the form of an abstract. ^bOwing to rounding, individual values sum to greater than 100%.

Figure 4.. A Priori Subgroup Analyses Evaluating the Association Between Postdiagnostic Statin Use and Risk of Prostate Cancer–Specific Mortality Among Men Receiving Androgen-Ablative Therapies

Includes 14 cohorts and 115 612 men. The diamond represents the pooled estimate, derived from generic inverse variance random-effects modeling. Each square represents the respective subgroup pooled estimate. The horizontal lines represent 95% CIs. Interstudy heterogeneity was assessed using the Cochran Q statistic and quantified with the I² statistic (>50% is considered substantial). ADT indicates androgen deprivation therapy; ARAT, androgen receptor axis–targeted therapy; CRPC, castration-resistant prostate cancer; CV, cardiovascular; HR, hazard ratio; HSPC, hormone-sensitive prostate cancer; NA, not applicable.