Randomized clinical trial of short or long interval between neoadjuvant chemoradiotherapy and surgery for rectal cancer

Background: The optimal timing of surgery following preoperative chemoradiotherapy (CRT) is controversial. This trial aimed to compare pathological complete response (pCR) rates obtained after an interval of 8weeks or less versus more than 8weeks. Methods: Patients with locally advanced rectal adenocarcinoma situated within 12cm of the anal verge (T3-4 or N+ disease) were randomized to undergo total mesorectal excision (TME) within 8weeks (classical interval, CI group) or after 8weeks (long interval, LI group) following CRT. Results: Among the 327 included patients (CI 160, LI 167), the pCR rate was significantly higher in the LI group than in the CI group (100 versus 186 per cent; P=0027). The highest pCR rate (29 percent) was observed between 10 and 11weeks. There was statistically significant disease regression in the LI group, with better stage (P=0004) and T category (P=0001) than in the CI group. There was no significant difference in surgical quality (rates of tumour-positive margins, TME quality, anastomotic leakage and intraoperative perforation) between the groups. The overall morbidity rate was 225 per cent in the CI group and 198 per cent in the LI group (P=0307). Regression analysis including sex, age, clinical stage, tumour location, tumour differentiation, TME quality, concomitant chemotherapy and interval to surgery revealed no statistically significant predictors of pCR. Conclusion: Disease regression and pCR rate are increased with an interval between CRT and surgery exceeding 8weeks. Registration number: NCT03287843.