Increasing the Interval Between Neoadjuvant Chemoradiotherapy and Surgery in Rectal Cancer A Meta-analysis of Published Studies

Objective:The aim of this meta-analysis was to demonstrate whether a longer interval between the end of neoadjuvant chemoradiotherapy (CRT) and surgery is associated with a better rate of pathological complete response (pCR) in rectal cancer.Background:The standard of care in locally advanced rectal cancer is preoperative, long course (5-fluorouracil-based) CRT. After this neoadjuvant CRT, surgical exploration is undertaken 6 to 8 weeks later.Methods:PubMed, EMBASE, the ISI Web of Science, and The Cochrane Library (CENTRAL) were searched systematically for prospective or retrospective studies reporting oncological results for intervals longer or shorter than 6 to 8 weeks between the end of CRT and surgery, in rectal cancer. The primary endpoint, reported as relative risk (RR), was the rate of pCR. Secondary endpoints were overall survival (OS), disease-free survival (DFS), R0 resection rates, sphincter preservations, and wound/anastomotic complications. A meta-analysis was performed, using the fixed- or random-effects model, with Review Manager 5.1.Results:Thirteen trials, including 3584 patients, were identified, and overall, an interval longer than 6 to 8 weeks from the end of neoadjuvant CRT and surgery significantly improved the pCR (RR = 1.42, 95% confidence interval: 1.19-1.68; P < 0.0001). Pathological complete responses increased from 13.7% to 19.5% in the longer interval group, and the OS, DFS, R0 resection rates, sphincter preservation, and complication rates were similar in the 2 groups.Conclusions:A longer waiting interval (more than the classical 6-8 weeks) from the end of preoperative CRT increases the rate of pCR by 6% in rectal cancer, with similar outcomes and complication rates. These results should be validated prospectively in a randomized trial.