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

Abstract

SummaryBackgroundPreoperative 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.MethodsWe 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.FindingsAt 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).InterpretationTaken 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.FundingMedical Research Council (UK) and the National Cancer Institute of Canada.

An overview of 25 years of incidence, treatment and outcome of colorectal cancer patients

“…Also, downstaging may have occurred after preoperative treatment with chemoradiotherapy or after preoperative short‐course radiotherapy followed by a long interval to surgery 39. However, the majority of patients in this database that received short‐course radiotherapy had surgery within an interval of 10 days after preoperative therapy, and downstaging is not observed in this group 40, 41. Most importantly, postoperative staging is the gold standard and clinical staging using CT and MRI is rather unreliable, especially regarding lymph node staging 18, 42…”

Laparoscopic extraperitoneal rectal cancer surgery: the clinical practice guidelines of the European Association for Endoscopic Surgery (EAES)

“…A Medical Research Council (MRC) trial including 1,350 patients demonstrated a significant reduction of local recurrence in patients receiving preoperative scRT compared with initial surgery with selective postoperative radiochemotherapy (4.4% versu 10.6% after 3 years). In addition, a relative improvement in diseasefree survival has been shown, whereas overall survival did not differ between the groups [33]. A number of randomised trials demonstrated the effectiveness of CRT (either post-or preoperatively).…”

Paradigm Shift in the Management of Rectal Cancer

“…It is accepted that preoperative radiotherapy is more efficacious than postoperative (adjuvant) treatment at achieving local control [24,25]. The two widely accepted approaches to preoperative treatment are either short course preoperative radiotherapy (SCPRT) or long course chemoradiotherapy (CRT).…”

“…The rational for SCPRT for most patients are the results of three large European trials [26][27][28] and the UK's CR07 trial [24] that reported improved local control and possibly improved survival for rectal cancer patients treated with SCPRT against those treated with surgery alone. However, some of these trials have been criticised for the lack of TME surgical resection in the surgery arm and the benefit observed has been labelled secondary to the effect of RT compensating for poor surgical quality.…”