Does the addition of chemotherapy (CT) to preoperative radiotherapy (preopRT) increase the pathological response in patients with resected rectal cancer : Report of the 22921 EORTC phase III trial

Abstract

3504 Background: This trial evaluates the addition of CT to preop RT, and the value of postop CT for improving survival in T3-T4 resectable rectal cancer. Eligibility : age < 80 y and WHO PS < 2. Arm 1: preopRT 45 Gy in 5 weeks (w). Arm 2 : preopRT + two 5 day CT courses ( 5-FU 350 mg/m2/d; LV : 20 mg/m2/d ), the 1st and 5th w of RT. Arm 3 : preopRT + four postop CT courses. Arm 4 : preopRT-CT + postop CT. We analyzed the pathological response. Methods: 1011 pts entered the trial : group 1-no preop CT (arms 1+3) : 505 pts; group 2- preop CT (arms 2+4) : 506 pts. Patients/tumour (T) : median age 63.2 y; male/female 73.1 %/27.9 %; T distance from anal verge : <5 cm : 49.1%; 6–10 cm : 43.7 %; >10 cm : 6.46 %; NA : 0,8 %; T stage : T3 : 89.5 %; T4 : 10 %. NA : 0.5 %. A resection was performed in 476 pts (94.3 %) and 473 pts (99.5 %) in Group 1 and 2 respectively. Results: Group 1 vs Group 2 : Median tumour length (mm) : 30 vs 25 (p = <0.0001). Extension into rectal wall : T0 : 5.3 % vs 14 % (p = >0.0001); PT0–2 : 42.9 % vs 58.1 % (p = < 0.0001). Median depth invasion beyond muscularis propria (mm) : 3 vs 2 (p = 0.061). Veinous (V) invasion 13.9 % vs 9.1 % (p = 0.021). Perineural (N) invasion 14.3 % vs 7.6 % (p = 0.001). Lymphatic (L) invasion 17.4 % vs 11.4 % (p = 0.008). Nodal invasion : 26.9 % vs 20.9 % (p = 0.031). Conclusions: The addition of 5-FU-LV to preopRT significantly reduced tumor size and pTN stage, and significant decreased LVN invasion rates. Longer follow-up is needed to assess the true impact on local control and survival. Supported in part by a grant from the French Research Ministry (PHRC 1992) and by NCI grants 2U10-CA11488–22 through 5U10-CA11488–32. No significant financial relationships to disclose.