Does timing of esophagectomy following neoadjuvant chemoradiation affect outcomes? A meta-analysis

Background: The optimal timing of esophagectomy after neoadjuvant chemoradiation treatment (nCRT) remains unclear. Here, a meta-analysis was conducted to determine whether prolonged interval between nCRT and surgery can affect the outcomes in esophageal cancer. Materials and methods: The databases PubMed, Embase, Web of Science, and Cochrane were systematically searched for studies reporting the outcomes in esophageal cancer according to the length of interval between nCRT and surgery. The primary outcome was rate of pathologic complete response (pCR), and the secondary outcomes included R0 resection rate, incidence of anastomotic leak, postoperative mortality, and two or five-year overall survival (OS). The intervals were classified into dichotomous (<= 7-8 weeks and > 7-8 weeks) for the pooled analysis, and a combined relative risk (RR) was calculated. Results: A total of 13 studies involving 15,086 patients were analyzed. The overall results indicated that an interval longer than 7-8 weeks between the end of nCRT and the surgery was significantly associated with an improved pCR rate (RR, 1.13; 95% confidence interval [CI], 1.05-1.21; P = 0.001). However, it was related to a higher 30-day surgical mortality (RR, 1.51; 95% CI, 1.19-1.92; P = 0.0006). The subgroup analyses only detected a significant association of the extended interval with pCR and the surgical mortality rate in adenocarcinoma patients. Moreover, an increased time interval resulted in a lower 2-year (RR, 0.94; 95% CI, 0.90-0.98; P = 0.002) and 5-year OS (RR, 0.88; 95% CI, 0.82-0.95; P = 0.0009). No association with R0 resection rate or anastomotic complication resulting from delayed resection was detected. Conclusions: Although increasing the time interval from nCRT to esophagectomy was associated with significantly higher pathologic complete response rates in esophageal cancer, delaying the surgery might be disadvantageous for the long-term survival.