Preoperative radiotherapy (preop RT) in rectal cancer: Impact of chemotherapy on the outcome—Long-term results of the randomized 22,921 phase III trial of EORTC.

Abstract

3560 Background: This 2x2 factorial design clinical trial evaluated the addition of Fluorouracil-based chemotherapy (CT) to preop RT and the use of adjuvant CT in patients with resectable T3-T4 M0 rectal cancer. The 5-year results showed that adding CT preoperatively or postoperatively had no significant effect on overall survival (OS) nor on disease-free survival (DFS) but a divergence seemed to emerge respectively at 2 and 5 years in the postop CT group. We report results with a median of 10.4 years. Methods: A total of 1011 patients were allocated in four treatment arms: preop RT ; preop RT + 2 CT courses ; preop RT + 4 postop CT courses ; preop RT-CT + postop CT. Preop RT was 45 Gy over 5 weeks. A one 5-day course of CT consisted of 5-Fu 350 mg/m²/d and Leucovorin 20 mg/m²/d. The effect of preop CT and adjuvant CT on OS and DFS was assessed by Logrank test (2-sided 5% significance level) stratified respectively for postop and for preop treatment. Written informed consent was obtained from all patients before randomization. Results: There is no significant difference in OS, nor in DFS between the groups receiving preop CT or not (p = 0.91 and p = 0.38 respectively). There is no significant difference in OS nor in DFS between the groups treated by postop CT or not (p = 0.32 and p = 0.29 respectively). The 10-year cumulative incidence of local recurrences is ~9 % in all the CT groups and 17.4 % in the preop RT alone group (p = 0.0044). The 10 year cumulative incidence of distant metastases (DM) is ~35 % in all treatment groups. Conclusions: With more that 10-years follow-up there is no benefit in rectal cancer by adding Fluorouracil-based chemotherapy preoperatively nor postoperatively to preop RT in terms of OS, DFS, nor in term of DM. Clinical trial information: 00002523.