Statin Use and Survival Among Men Receiving Androgen-Ablative Therapies for Advanced Prostate Cancer

Abstract

ImportanceEpidemiological evidence supports a role for statins in improving survival in advanced prostate cancer, particularly among men receiving androgen-ablative therapies.ObjectiveTo 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 SourcesThis 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 SelectionObservational studies reporting associations of concurrent statin use and survival outcomes (in hazard ratios [HRs]).Data Extraction and SynthesisTwo 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 MeasuresOverall mortality and prostate cancer–specific mortality (PCSM).ResultsTwenty-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 RelevanceThe 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.

Circulating Lipid Profiles Associated With Resistance to Androgen Deprivation Therapy in Localized Prostate Cancer

“…25-27 The combined use of statins with ADT was associated with improved overall survival and reduction in prostate cancer–specific mortality. 28 Interestingly, we observed that a higher proportion of patients in the N2 group (more responders) of the neoadjuvant cohort were already on statin medication at the start of the trials compared with the N1 group (33% v 13%, chi-squared test P = .02). However, we are unable to conclude if statin medication contributed to the lower plasma levels of sphingolipids of the N2 group without controlled conditions (eg, length of treatment time and prestatin plasma levels are unknown).…”

A Proposal for the Comprehensive Care of Men on Androgen Deprivation Therapy: Recommendations From the Multidisciplinary Prostate Cancer 360 Working Group

“…In a meta-analysis of 25 cohort studies that included 119,878 patients with PCa, concurrent statin use was associated with improved overall survival by 27% and PCa-specific mortality by 35%. 19 Furthermore, based on promising data from early-stage trials and observational studies, the effect of atorvastatin on PCa progression during ADT treatment is being investigated in an ongoing randomized placebo-controlled phase 3 trial. 20 While high-quality data on the effects of statins on cardiovascular and cancer-related mortality are still needed, the PC360 Working Group felt that the extant effectiveness data and the minimal risks associated with statin use were sufficient to recommend consideration of concurrent moderate-intensity statin initiation in most patients receiving ADT.…”

A retrospective study on the effect of statins on mortality and antimicrobial resistance among patients with <i>Staphylococcus aureus</i> bloodstream infection

“…Many studies have confirmed that statins can reduce the incidence rate of endometrial cancer, ovarian cancer, esophageal cancer, gastric cancer and colorectal cancer [ 16 , 17 ]. In addition, statins can also reduce the mortality of patients with esophageal cancer, gastric cancer, colorectal cancer, prostate cancer and breast cancer [ 17 , 18 ].…”