Cochrane Institute of Primary Care and Public Health, Cardiff University, Cardiff, United Kingdom.
Institute of Food, Nutrition and Health, University of Reading, Reading, United Kingdom.
PLoS One. 2018 Sep 25;13(9):e0203957. doi: 10.1371/journal.pone.0203957. eCollection 2018.
Evidence is growing that low-dose aspirin used as an adjuvant treatment of cancer is associated with an increased survival and a reduction in metastatic spread. We therefore extended up to August 2017 an earlier systematic search and meta-analyses of published studies of low-dose aspirin taken by patients with a diagnosis of cancer.
Searches were completed in Medline and Embase to August 2017 using a pre-defined search strategy to identify reports of relevant studies. References in all the selected papers were scanned. Two reviewers independently applied pre-determined eligibility criteria and extracted data on cause-specific cancer deaths, overall mortality and the occurrence of metastatic spread. Meta-analyses were then conducted for different cancers and heterogeneity and publication bias assessed. Sensitivity analyses and attempts to reduce heterogeneity were conducted.
Analyses of 29 studies reported since an earlier review up to April 2015 are presented in this report, and these are then pooled with the 42 studies in our earlier publication. Overall meta-analyses of the 71 studies are presented, based on a total of over 120 thousand patients taking aspirin. Ten of the studies also give evidence on the incidence of metastatic cancer spread. There are now twenty-nine observational studies describing colorectal cancer (CRC) and post-diagnostic aspirin. Pooling the estimates of reduction by aspirin which are reported as hazard ratios (HR), gives an overall HR for aspirin and CRC mortality 0.72 (95% CI 0.64-0.80). Fourteen observational studies have reported on aspirin and breast cancer mortality and pooling those that report the association with aspirin as a hazard ratio gives HR 0.69 (0.53-0.90). Sixteen studies report on aspirin and prostate cancer mortality and a pooled estimate yields an HR of 0.87 (95% CI 0.73-1.05). Data from 12 reports relating to other cancers are also listed. Ten studies give evidence of a reduction in metastatic spread; four give a pooled HR 0.31 (95% CI 0.18, 0.54) and five studies which reported odds ratio of metastatic spread give OR 0.79 (0.66 to 0.95).
Being almost entirely from observational studies, the evidence of benefit from aspirin is limited. There is heterogeneity between studies and the results are subject to important biases, only some of which can be identified. Nevertheless, the evidence would seem to merit wide discussion regarding whether or not it is adequate to justify the recommendation of low-dose therapeutic aspirin, and if it is, for which cancers?
越来越多的证据表明,低剂量阿司匹林作为癌症的辅助治疗与生存率的提高和转移扩散的减少有关。因此,我们将之前的系统搜索和对低剂量阿司匹林治疗癌症患者的已发表研究的荟萃分析扩展到 2017 年 8 月。
在 Medline 和 Embase 中进行搜索,直至 2017 年 8 月,使用预先确定的搜索策略来确定相关研究报告。扫描所有选定论文的参考文献。两位审查员独立应用预先确定的合格标准,并提取有关特定癌症死亡、总死亡率和转移扩散发生的数据。然后对不同癌症进行荟萃分析,并评估异质性和发表偏倚。进行敏感性分析并尝试减少异质性。
本报告介绍了自上次综述以来至 2015 年 4 月报告的 29 项研究的分析结果,然后将这些研究与我们之前出版物中的 42 项研究进行汇总。基于超过 120,000 名服用阿司匹林的患者,呈现了对 71 项研究的总体荟萃分析。其中 10 项研究还提供了转移性癌症扩散发生率的证据。现在有 29 项观察性研究描述了结直肠癌(CRC)和诊断后阿司匹林的情况。汇总报告的阿司匹林与 CRC 死亡率相关的风险比(HR),阿司匹林与 CRC 死亡率的总体 HR 为 0.72(95% CI 0.64-0.80)。14 项观察性研究报告了阿司匹林与乳腺癌死亡率的关系,汇总那些将阿司匹林与危险比相关联的研究结果,HR 为 0.69(0.53-0.90)。16 项研究报告了阿司匹林与前列腺癌死亡率的关系,汇总估计值得出 HR 为 0.87(95% CI 0.73-1.05)。还列出了与其他癌症相关的 12 项研究的结果。10 项研究表明转移性扩散减少;4 项汇总 HR 为 0.31(95% CI 0.18, 0.54),5 项报告转移扩散优势比的研究结果为 OR 0.79(0.66 至 0.95)。
由于几乎完全来自观察性研究,阿司匹林的益处证据有限。研究之间存在异质性,结果受到重要偏倚的影响,其中只有一部分偏倚可以识别。然而,证据似乎值得广泛讨论,即是否足以证明推荐低剂量治疗性阿司匹林合理,以及如果合理,对于哪些癌症?