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


METHODS
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.


RESULTS
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).


CONCLUSIONS
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.
Sebag-Montefiore
David
D
St James's University Hospital, Leeds, UK.
Stephens
Richard J
RJ
Steele
Robert
R
Monson
John
J
Grieve
Robert
R
Khanna
Subhash
S
Quirke
Phil
P
Couture
Jean
J
de Metz
Catherine
C
Myint
Arthur Sun
AS
Bessell
Eric
E
Griffiths
Gareth
G
Thompson
Lindsay C
LC
Parmar
Mahesh
M
D000230:Adenocarcinoma / Q000401:mortality / Q000532:radiotherapy* / Q000601:surgery; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000517:prevention & control; D011182:Postoperative Care; D011300:Preoperative Care; D011788:Quality of Life; D012004:Rectal Neoplasms / Q000401:mortality / Q000532:radiotherapy* / Q000601:surgery; D016019:Survival Analysis; D006113:United Kingdom