Fokas E, et al. - Among patients with stage II or III rectal cancer enrolled in this multicenter, randomized, phase II trial utilizing a pick-the-winner design, researchers assessed if pathologic complete response (pCR) can be increased by 25% following total neoadjuvant therapy vs the standard 15% following preoperative chemoradiotherapy (CRT). Participants were allocated to either induction chemotherapy using three cycles of fluorouracil, leucovorin, and oxaliplatin before fluorouracil/oxaliplatin CRT (50.4 Gy) in group A or to consolidation chemotherapy after CRT in group B. Among 311 patients included, 156 in group A and 150 in group B were evaluable. Compared with group A, better compliance with CRT but worse compliance with chemotherapy was seen with up-front CRT followed by chemotherapy. Evaluating if improved pCR in group B results in better oncologic outcomes requires long-term follow-up.