Tailored Strategy for Locally-Advanced Rectal Carcinoma (GRECCAR 4): Long-term Results from a Multicenter, Randomized, Open-Label, Phase 2 Trial.

BACKGROUND Systematic preoperative radiochemotherapy and total mesorectal excision are standard-of-care for locally-advanced rectal carcinoma. Some patients can be over- or undertreated. OBJECTIVE Long-term oncological, functional and late morbidity outcomes after tailored radiochemotherapy and induction high-dose chemotherapy. DESIGN Prospective, phase II, multicenter, open-label study at 16 tertiary centers in France. SETTINGS Patients operated by surgeons from the French GRECCAR group. PATIENTS 206 patients were randomly assigned to treatment: good responders after chemotherapy (≥75% tumor volume reduction) to immediate surgery (arm A) or standard radiochemotherapy (Cap 50) plus surgery (arm B); poor responders to Cap 50 (arm C) or intensive radiochemotherapy (Cap 60 (60 Gy irradiation) (arm D) before surgery. INTERVENTIONS Tailored treatment according to MR response to induction CT. RESULTS After induction treatment, 194 patients were classified as good (n=30, 15%) or poor (n=164, 85%) responders, and included in arms A and B (16 and 14 patients) or C and D (113 and 51 patients). The primary objective was obtained: R0 resection rates [90% confidence interval] in the four arms respectively were 100% [74-100], 100% [85-100], 83% [72-91], and 88% [77-95]. At 5 years, rates were: overall survival 90% [47.3-98.5], 93.3% [61.3-99.0], 84.3% [71.0-91.8], 86.1% [71.6-93.5]; disease-free survival 80% [40.9-94.6], 89.5% [64.1-97.3], 72.9% [58.5-82.9], 72.8% [57.7-83.2]; local recurrence 0, 0, 2.1% [0.3-13.9], 9.3% [3.6-23.0]; metastasis 20% [5.4-59.1], 10.5% [2.7-35.9], 18% [31.8-94.6], 18.8% [10.2-33.0]. Late morbidity and quality of life evaluations showed no significant difference between arms. LIMITATIONS limitations due to the small number of patients randomized in the good responder arms, especially arm A without radiotherapy. CONCLUSION Tailoring preoperative radiochemotherapy-based on induction treatment response appears to be promising. Future prospective trials should confirm this strategy. See Video Abstract at http://links.lww.com/DCR/B761.ClinicalTrials.gov Identifier: NCT01333709.