Effect of aspirin use on neoadjuvant chemoradiotherapy for rectal cancer: a meta-analysis with trial sequential analysis

Background Numerous studies have reported the preventive and protective effects of aspirin in patients with rectal cancer. However, it is not clear whether aspirin can be used as an assistance drug in preoperative neoadjuvant chemoradiotherapy. Therefore, this study will explore the efficacy of aspirin as an adjuvant agent in rectal cancer neoadjuvant chemoradiotherapy. Methods A literature search was performed using the electronic platforms to obtain relevant research studies published up to Jan 2020. The search was limited to papers published in English or Chinese language. Confidence intervals of research endpoints in each study were extracted and merged. The meta-analysis was performed using Stata12.0 software. Furthermore, we performed trial sequential analysis (TSA) to evaluate the robustness of our findings and to obtain a more conservative estimation. Results A total of 5 studies including 977 patients were identified to be eligible for this meta-analysis. Compared with control group, aspirin group significantly increased pathologic complete response rate from 16.5 to 22.3% (RR 1.41, 95% CI 1.01–1.96, P = 0.041), partial remission rate from 21.8 to 45.7% (RR 1.87, 95% CI 1.37–2.54, P < 0.001), and tumor down-staging rate from 44.4 to 63.8% (RR 1.43, 95% CI 1.17–1.75, P = 0.001). Moreover, aspirin group can reduce local recurrence rate (RR 0.37, 95% CI 0.17–0.84, P = 0.017), improve 3-year survival rate (RR 1.24, 95% CI 1.12–1.36, P < 0.001), and 5-year survival rate (RR 1.29, 95% CI 1.14–1.46, P < 0.001). TSA shows that the meta-analysis results of pathologic complete response rate and local recurrence rate may be a false positive. Furthermore, the meta-analysis results of other study endpoints were further confirmed by TSA. Conclusion Aspirin, as an adjuvant agent, can enhance the effect of neoadjuvant chemoradiotherapy and improve the prognosis of patients with rectal cancer. Neoadjuvant therapy combined with aspirin may be considered a better option for preoperative rectal cancer patients.