Stopsack Konrad H, Ziehr David R, Rider Jennifer R, Giovannucci Edward L
Department of Epidemiology, Harvard T.H. Chan School of Public Health, 677 Huntington Ave, Boston, MA, 02115, USA.
Harvard Medical School, 25 Shattuck St, Boston, MA, 02115, USA.
Cancer Causes Control. 2016 Jan;27(1):105-13. doi: 10.1007/s10552-015-0687-0. Epub 2015 Nov 4.
Observational studies report conflicting results on the association between metformin exposure and prostate cancer outcomes. This meta-analysis summarizes studies reporting overall survival, prostate cancer-specific mortality, and biochemical recurrence.
PubMed and Embase were systematically reviewed to identify studies investigating the association between metformin use and clinical endpoints among men with prostate cancer while taking confounding by diabetes diagnosis into account. Pooled risk estimates (hazard ratios, HRs) and 95 % confidence intervals (CIs) were calculated using random-effects models. Sensitivity analyses for quality components and factors for heterogeneity were conducted.
Of 549 articles identified, nine retrospective cohort studies representing 9,186 patients were included. There was significant heterogeneity between studies, and studies differed in quality. Metformin use was associated with improved overall survival in studies with clear risk window definition (HR 0.88, 95 % CI 0.86-0.90, p < 0.001) and in studies with potential immortal time bias (HR 0.52, 95 % CI 0.41-0.65, p < 0.001). No significant association with prostate cancer-specific mortality was detected (HR 0.76, 95 % CI 0.44-1.31, p = 0.33). Metformin use was associated with a decreased risk of biochemical recurrence (HR 0.79, 95 % CI 0.63-1.00, p = 0.047).
This meta-analysis suggests a benefit of metformin in men with diabetes and prostate cancer. However, further carefully designed studies are needed to confirm findings and to assess potential generalization to non-diabetic, non-white, and less aggressively treated men with prostate cancer.
观察性研究报告了二甲双胍暴露与前列腺癌预后之间关联的相互矛盾的结果。本荟萃分析总结了报告总生存期、前列腺癌特异性死亡率和生化复发情况的研究。
系统检索了PubMed和Embase，以识别在考虑糖尿病诊断混杂因素的情况下，研究前列腺癌男性使用二甲双胍与临床终点之间关联的研究。使用随机效应模型计算合并风险估计值（风险比，HR）和95%置信区间（CI）。对质量成分和异质性因素进行了敏感性分析。
在识别出的549篇文章中，纳入了9项回顾性队列研究，共9186例患者。研究之间存在显著异质性，且研究质量不同。在风险窗口定义明确的研究中（HR 0.88，95%CI 0.86 - 0.90，p < 0.001）以及存在潜在不朽时间偏倚的研究中（HR 0.52，95%CI 0.41 - 0.65，p < 0.001），使用二甲双胍与总生存期改善相关。未检测到与前列腺癌特异性死亡率有显著关联（HR 0.76，95%CI 0.44 - 1.31，p = 0.33）。使用二甲双胍与生化复发风险降低相关（HR 0.79，95%CI 0.63 - 1.00，p = 0.047）。
本荟萃分析表明二甲双胍对糖尿病合并前列腺癌男性有益。然而，需要进一步精心设计的研究来证实这些发现，并评估对非糖尿病、非白人以及前列腺癌治疗不积极的男性的潜在适用性。
