Journal Article

Preoperative radiotherapy versus selective postoperative chemoradiotherapy in patients with rectal cancer (MRC CR07 and NCIC-CTG C016): a multicentre, randomised trial

Khanna, Subhash, Couture, Jean, Thompson, Lindsay C, Stephens, Richard J, Sebag-Montefiore, David, Griffiths, Gareth, Bessell, Eric, Parmar, Mahesh, Grieve, Robert, Quirke, Phil, Monson, John, Steele, Robert, Myint, Arthur Sun, de Metz, Catherine

2009

Overview

Preoperative or postoperative radiotherapy reduces the risk of local recurrence in patients with operable rectal cancer. However, improvements in surgery and histopathological assessment mean that the role of radiotherapy needs to be reassessed. We compared short-course preoperative radiotherapy versus initial surgery with selective postoperative chemoradiotherapy. We undertook a randomised trial in 80 centres in four countries. 1350 patients with operable adenocarcinoma of the rectum were randomly assigned, by a minimisation procedure, to short-course preoperative radiotherapy (25 Gy in five fractions; n=674) or to initial surgery with selective postoperative chemoradiotherapy (45 Gy in 25 fractions with concurrent 5-fluorouracil) restricted to patients with involvement of the circumferential resection margin (n=676). The primary outcome measure was local recurrence. Analysis was by intention to treat. This study is registered, number ISRCTN 28785842. At the time of analysis, which included all participants, 330 patients had died (157 preoperative radiotherapy group vs 173 selective postoperative chemoradiotherapy), and median follow-up of surviving patients was 4 years. 99 patients had developed local recurrence (27 preoperative radiotherapy vs 72 selective postoperative chemoradiotherapy). We noted a reduction of 61% in the relative risk of local recurrence for patients receiving preoperative radiotherapy (hazard ratio [HR] 0·39, 95% CI 0·27–0·58, p<0·0001), and an absolute difference at 3 years of 6·2% (95% CI 5·3–7·1) (4·4% preoperative radiotherapy vs 10·6% selective postoperative chemoradiotherapy). We recorded a relative improvement in disease-free survival of 24% for patients receiving preoperative radiotherapy (HR 0·76, 95% CI 0·62–0·94, p=0·013), and an absolute difference at 3 years of 6·0% (95% CI 5·3–6·8) (77·5% vs 71·5%). Overall survival did not differ between the groups (HR 0·91, 95% CI 0·73–1·13, p=0·40). Taken with results from other randomised trials, our findings provide convincing and consistent evidence that short-course preoperative radiotherapy is an effective treatment for patients with operable rectal cancer. Medical Research Council (UK) and the National Cancer Institute of Canada.

• Publisher: Elsevier Ltd,Elsevier,Elsevier Limited,Lancet Publishing Group
• Subject: Adenocarcinoma - mortality / Adenocarcinoma - radiotherapy / Adenocarcinoma - surgery / Adult / Aged / Aged, 80 and over / Biological and medical sciences / Chemotherapy / Chemotherapy, Adjuvant / Clinical trials / Colorectal cancer / Disease-Free Survival / Female / Follow-Up Studies / Gastroenterology. Liver. Pancreas. Abdomen / General aspects / Humans / Internal Medicine / Male / Medical research / Medical sciences / Middle Aged / Neoplasm Recurrence, Local - prevention & control / Postoperative Care / Preoperative Care / Quality of Life / Radiation therapy / Rectal Neoplasms - mortality / Rectal Neoplasms - radiotherapy / Rectal Neoplasms - surgery / Stomach. Duodenum. Small intestine. Colon. Rectum. Anus / Surgeons / Survival Analysis / Tumors / United Kingdom