Aspirin Use Improves Survival after Cancer Diagnosis: A Systematic Review and Meta-Analysis of Fifty-Seven Studies

Abstract

Background: Aspirin has been widely used as treatment for inflammation, pain and cardiovascular events, and recently some studies found that patients of cancer with aspirin use seemed to have longer survival. However, the supporting data varied, and the arguments existed among studies. To better understand this issue, we conducted this systematic review and meta-analysis to investigate whether patients of cancer with aspirin use had longer survival. Methods: This study has been registered in PROSPERO (No· CRD42018102280). We searched the PubMed, Web of Science and Embase for studies about aspirin use and survival of cancer published before May 2018, and the references of related studies were also reviewed. The primary outcomes were cancer-specific survival and overall survival for patients of cancer. In meta-analysis, pooled odds ratios (OR) and 95% confidence intervals (CI) were estimated with random-effects or fixed-effects model according to the heterogeneity which was estimated by Q statistic. Subgroup analysis was performed to identify the associations between aspirin use and survival of different kinds of cancers, and the influences of prediagnosis or postdiagnosis aspirin use and duration of aspirin use were also assessed. For colorectal cancer, we specially assessed the influence of PIK3CA mutation status and prostaglandin-endoperoxide synthase 2 (PTGS2) expression in this study. Findings: Totally 57 observational studies with 17 kinds of cancers and 1274 933 participants were included. Compared with aspirin nonusers, patients of cancer with postdiagnosis aspirin use had both prolonged cancer-specific survival (OR 0·86; 95% CI 0·72-0·99; P heterogeneity <0·001) and overall survival (OR 0·81; 95% CI 0·67-0·95; P heterogeneity <0·001), while prediagnosis aspirin use showed no significant associations. Subgroup analysis indicated that patients of colorectal cancer with aspirin use had significantly improved cancer-specific survival (OR 0·81; 95% CI 0·68-0·95) and overall survival (OR 0·78; 95% CI 0·66-0·90) when compared with aspirin nonusers, while patients of oesophageal cancer showed improved overall survival (OR 0·63; 95% CI 0·31-0·94), and patients of breast cancer showed improved cancer-specific survival (OR 0·83; 95% CI 0·68-0·98). The duration-response analysis showed that only patients with aspirin use ≥ 5 years had prolonged cancer-specific survival (OR 0·82; 95% CI 0·70-0·94), while patients with aspirin use < 2·5 years or < 5 years didn't have significant results. For patients of colorectal cancer with aspirin use, specially we found that compared with aspirin nonusers, those with PIK3CA mutation had both improved cancer-specific survival (OR 0·33; 95% CI 0·11-0·55) and overall survival (OR 0·67; 95% CI 0·44-0·90), and those with high or positive PTGS2 expression was associated with prolonged overall survival (OR 0·65; 95% CI 0·50-0·80). Interpretation: Our study suggested that not all patients of cancer with aspirin use, but those with postdiagnosis aspirin use might have longer survival, and only when aspirin use at least 5 years were associated with improved survival. We also found that patients of oesophageal cancer, breast cancer, and specially patients of colorectal cancer with PIK3CA mutation or high PTGS2 expression, could have more survival benefits with aspirin use. Trial Registry: This study has been registered in PROSPERO (No· CRD42018102280). Funding: This work was supported by National Natural Science Foundation of China (No·30901427). Declaration of Interest: We declare no competing interests.