Final Results of the GRECCAR-6 Trial on Waiting Period Following Neoadjuvant Radiochemotherapy for Locally Advanced Rectal Cancer: 5 Years of Follow-up.

Abstract

Background: The potential oncological benefit of extending the waiting period between neoadjuvant radiochemotherapy and surgical resection for rectal cancer is debated.

Objective: To evaluate the impact of prolonging this waiting period on the 5-year oncological prognosis and 2-year functional result of locally advanced rectal adenocarcinoma.

Design: Phase III, multicenter, randomized, open-label, parallel-group, controlled trial.

Settings: Patients were enrolled from 24 colorectal centers.

Patients: Patients with non-metastatic mid or lower cT3-4 or TxN+ rectal adenocarcinoma who had received radio-chemotherapy (45 to 50 Gy with fluorouracil or capecitabine).

Intervention: Patients were randomly assigned to undergo total mesorectal excision either 7 weeks (W7) or 11 weeks (W11) after radiochemotherapy.

Main outcomes measures: Overall survival and disease-free survival at 5 years of follow-up and low anterior resection syndrome score assessed after 2 years of follow-up.

Results: Among 265 patients enrolled, 133 were randomized in the 7-week group and 132 in the 11-week group. Twelve patients were excluded as they did not undergo resection. Among 253 patients analyzed, 5-year overall survival was not different between the two groups (81.6% in 7-week group versus 82.6% in 11-week group, p = 0.827), as well as for the 5-year disease-free survival (70.4% in 7-week group versus 69.5% in 11-week group, p = 0.856). No difference was observed between the two groups for distant recurrence (27.4% in 7-week group versus 25.7% in 11-week group, p = 0.777) or local recurrence (8.4% in 7-weeks group versus 10.2% in 11-week group, p = 0.543). Low anterior resection syndrome score was similar between the 7-week (25.0 IQR [15.0-34.0]) and 11-week groups (23.0 IQR[14.2-32.0], p = 0.743).

Limitations: The response rate to the LARS questionnaire was only 52%.

Conclusions: Extending the waiting period between radiochemotherapy and resection from 7 to 11 weeks does not modify the 5-year oncological prognosis in rectal cancer and the 2-year low anterior resection occurrence.