title: Preoperative radiotherapy versus selective postoperative chemoradiotherapy in patients with rectal cancer (MRC CR07 and NCIC-CTG C016): a multicentre, randomised trial.
abstract: 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.
authors.affiliation: St James's University Hospital, Leeds, UK.
authors.forename: David
authors.initials: D
authors.lastname: Sebag-Montefiore
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Stephens
authors.forename: Robert
authors.initials: R
authors.lastname: Steele
authors.forename: John
authors.initials: J
authors.lastname: Monson
authors.forename: Robert
authors.initials: R
authors.lastname: Grieve
authors.forename: Subhash
authors.initials: S
authors.lastname: Khanna
authors.forename: Phil
authors.initials: P
authors.lastname: Quirke
authors.forename: Jean
authors.initials: J
authors.lastname: Couture
authors.forename: Catherine
authors.initials: C
authors.lastname: de Metz
authors.forename: Arthur Sun
authors.initials: AS
authors.lastname: Myint
authors.forename: Eric
authors.initials: E
authors.lastname: Bessell
authors.forename: Gareth
authors.initials: G
authors.lastname: Griffiths
authors.forename: Lindsay C
authors.initials: LC
authors.lastname: Thompson
authors.forename: Mahesh
authors.initials: M
authors.lastname: Parmar
mesh_terms: 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