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 8 weeks or less versus more than 8 weeks.
Methods: Patients with locally advanced rectal adenocarcinoma situated within 12 cm of the anal verge (T3-4 or N+ disease) were randomized to undergo total mesorectal excision (TME) within 8 weeks (classical interval, CI group) or after 8 weeks (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 (10·0 versus 18·6 per cent; P = 0·027). The highest pCR rate (29 per cent) was observed between 10 and 11 weeks. There was statistically significant disease regression in the LI group, with better stage (P = 0·004) and T category (P = 0·001) 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 22·5 per cent in the CI group and 19·8 per cent in the LI group (P = 0·307). 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 8 weeks. Registration number: NCT03287843 (http://www.clinicaltrials.gov).
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