Timing of surgery after neoadjuvant chemoradiotherapy affects oncologic outcomes in patients with esophageal cancer

The optimal time interval between neoadjuvant chemoradiotherapy (nCRT) and esophagectomy in esophageal cancer has not been defined.To evaluate whether a prolonged time interval between the end of nCRT and surgery has an effect on survival outcome in esophageal cancer patients.We searched PubMed, Embase, Web of Science, the Cochrane Library, Wanfang and China National Knowledge Infrastructure databases for relevant articles published before November 16, 2019, to identify potential studies that evaluated the prognostic role of different time intervals between nCRT and surgery in esophageal cancer. The hazard ratios and 95% confidence intervals (95%CI) were merged to estimate the correlation between the time intervals and survival outcomes in esophageal cancer, esophageal squamous cell carcinoma and adenocarcinoma using fixed- and random-effect models.This meta-analysis included 12621 patients from 16 studies. The results demonstrated that esophageal cancer patients with a prolonged time interval between the end of nCRT and surgery had significantly worse overall survival (OS) [hazard ratio (HR): 1.107, 95%CI: 1.014-1.208, P = 0.023] than those with a shorter time interval. Subgroup analysis showed that poor OS with a prolonged interval was observed based on both the sample size and HRs. There was also significant association between a prolonged time interval and decreased OS in Asian, but not Caucasian patients. In addition, a longer wait time indicated worse OS (HR: 1.385, 95%CI: 1.186-1.616, P < 0.001) in patients with adenocarcinoma.A prolonged time interval from the completion of nCRT to surgery is associated with a significant decrease in OS. Thus, esophagectomy should be performed within 7-8 wk after nCRT.