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Thank you for the opportunity to respond to Professor Bujko's interesting letter regarding the need for a prospective randomized controlled trial to examine the timing of surgery following chemoradiotherapy in rectal cancer.The original Lyon trial randomly assigned patients between surgery at 2 weeks and 6 weeks. The greater downstaging observed in the 6 weeks arm resulted in surgery at 6 weeks after completion of radiotherapy becoming the standard of care.1We agree with Professor Bujko that increasing the time interval from completion of surgery to 10 weeks or 12 weeks is a change in practice that has insufficient evidence base and runs the risk of tumor regrowth, yet many centers have chosen to undertake surgery beyond the 6-week standard in a nonclinical trial setting. In our prospective randomized 6 vs 12 trial, patients in both arms are restaged at 6 weeks, and, if there is evidence of tumor progression, patients undergo surgery without any further delay. The careful documentation of disease status at the 6-week point is a crucial aspect in establishing the safety of prolonging the time interval. We believe that the safety and efficacy of deferring surgery beyond 6 weeks can only be established in a trial setting.Professor Bujko notes the failure of the greater downstaging observed in preoperative therapy trials to have an impact on local recurrence. However, in the years following those trials, circumferential margin status has emerged as the major influence on local recurrence rates; it was not considered in these earlier trials. Therefore, we concur with Professor Bujko's suggestion that the additional tumor shrinkage observed in patients with a greater delay could make the difference between resectability or not and, thus, circumferential margin status, which is now being regarded as a good surrogate for the risk of pelvic recurrence.2 Comparison of rates of surgical resection with clear circumferential margins will be specifically evaluated in the randomized arms of the 6 vs 12 trial.The impact of downstaging on recurrence rates is only part of a number of outcome measures of relevance to the timing of surgery following chemoradiotherapy in locally advanced rectal cancer. Postoperative complications, sphincter-preserving surgery, toxicity, disease-free survival, and overall survival are all important end points that need answers to end the controversy. The only way to establish this is by a prospective randomized controlled study.Gina Brown, M.D., F.R.C.R.Jessica Evans, M.R.C.S.Diana Tait, M.D., F.R.C.P.Ian Swift, F.R.C.S.Paris Tekkis, M.D., F.R.C.S.Andrew Wotherspoon, F.R.C.Path.Ian Chau, M.D., M.R.C.P.