Two-Week Course versus Conventionally Fractionated Preoperative Chemoradiotherapy Followed by Total Mesorectal Excision in Locally Advanced Rectal Cancer (Twoarc Trial): A Phase III Randomized Clinical Trial.

OBJECTIVE This phase III randomized trial compared two-week course of preoperative chemoradiotherapy (CRT) with conventional long-course CRT followed by total mesorectal excision (TME) in rectal cancer. BACKGROUND Two-week schedule of hypofractionated radiotherapy with concurrent capecitabine showed favorable tumor response and safety in a previous phase II study. METHODS This study enrolled 338 rectal cancer patients with cT3-4N0-2M0 to receive either standard long-course preoperative radiotherapy (50.4 Gy in 28 fractions over 5-6 wk) or two-week course of radiation (33 Gy in 10 fractions over two weeks) with concurrent intravenous 5-fluorouracil or oral capecitabine. The primary endpoint was downstaging (ypT0-2N0M0) rate. TME was performed 6-10 weeks after the completion of radiotherapy. RESULTS Of 338 patients, 167 received standard long-course CRT and 171 received two-week course of CRT. ypCR was achieved in 26 (15.6%) patients of the standard-course arm and in 25 (14.6%) patients of the two-week-course arm (P=0.807). Downstaging was achieved in 67 (40.1%) patients of the standard-course arm and in 62 (36.3%) patients of the two-week-course arm (P=0.465). Sphincter preservation (91.0% vs. 95.3%, P=0.116) and positive circumferential resection margin (9.0% vs. 14.6%, P=0.109) rates were not significantly different between the two arms. The two-week arm demonstrated significantly lower incidence of grade 2 or higher gastrointestinal toxicity than the standard arm (5.8% vs. 13.2%, P=0.021). CONCLUSIONS This phase III randomized controlled trial suggests that two-week course of preoperative CRT provides comparable tumor response as standard long-course CRT in rectal cancer, with potential advantages of shorter treatment duration and lower gastrointestinal toxicity.