Division of Urology, Department of Surgery, University of Toronto, Toronto, Ontario, Canada.
Women's College Research Institute, Toronto, Ontario, Canada.
JAMA Netw Open. 2022 Nov 1;5(11):e2242676. doi: 10.1001/jamanetworkopen.2022.42676.
Epidemiological evidence supports a role for statins in improving survival in advanced prostate cancer, particularly among men receiving androgen-ablative therapies.
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).
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.
Observational studies reporting associations of concurrent statin use and survival outcomes (in hazard ratios [HRs]).
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.
Overall mortality and prostate cancer-specific mortality (PCSM).
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.
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.
流行病学证据支持他汀类药物在改善晚期前列腺癌患者的生存方面发挥作用,尤其是在接受去势治疗的男性中。
研究接受去势治疗(ADT)或雄激素受体轴靶向治疗(ARAT)的前列腺癌患者中,他汀类药物使用与生存之间的关联。
本系统评价和荟萃分析使用了 MEDLINE、EMBASE、Epub 提前印刷、Cochrane 临床试验、Cochrane 系统评价和 Web of Science 从成立到 2022 年 9 月 6 日的来源。
报告他汀类药物使用与生存结果(风险比[HR])相关的观察性研究。
两位作者独立提取所有数据。使用随机效应模型的通用逆方差法汇总多变量 HR 的汇总估计值,并使用 95%置信区间。进行了预先指定的亚组和敏感性分析,并评估了异质性、研究质量和发表偏倚。使用 GRADE(推荐评估、制定和评估)方法评估证据的可信度。
总死亡率和前列腺癌特异性死亡率(PCSM)。
纳入了 25 项队列研究,涉及 119878 名男性(65488 名他汀类药物使用者[55%]),其中超过 74416 人死亡。同时使用他汀类药物可降低 27%的总死亡率风险(HR,0.73[95%CI,0.66-0.82];I2=83%)和 35%的 PCSM 风险(HR,0.65[95%CI,0.58-0.73];I2=74%),这两个估计值都存在很大的异质性。亚组分析确定了与单独 ADT 相比,接受 ARAT 的男性使用他汀类药物与 PCSM 相关的优势(HR,0.40[95%CI,0.30-0.55]vs 0.68[95%CI,0.60-0.76];差异 P =.002)。这两个结果的证据置信度均被评为低。
这项荟萃分析的结果表明,在接受去势治疗的晚期前列腺癌男性中,同时使用他汀类药物与降低总死亡率和 PCSM 相关。这些发现受到数据的观察性质和未解释的研究间异质性的限制。需要进行随机临床试验来验证这些结果。