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CR07

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

N = 1,350NCT00003422

Population
Patients with operable adenocarcinoma of the rectum
Design
Multicentre randomised trial in 80 centres in four countries, recruiting from March 1998 to August 2005. 1350 patients with operable adenocarcinoma of the rectum were randomised 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 fluorouracil), restricted to patients with involvement of the circumferential resection margin (n=676). Analysis was by intention to treat. The trial was designed to test whether selective postoperative chemoradiotherapy was non-inferior to preoperative radiotherapy; because most UK clinicians had adopted the selective approach by 2006, the results were analysed as superiority of preoperative radiotherapy. Of 77 patients in the selective group whose circumferential resection margin was involved (1 mm or less), 53 received chemoradiotherapy. Registered as ISRCTN 28785842 (ClinicalTrials.gov NCT00003422).
Primary endpoint
Local recurrence
Arms
  • Initial surgery with selective postoperative chemoradiotherapy (control, n = 676): Initial surgery; postoperative chemoradiotherapy (45 Gy in 25 fractions with concurrent fluorouracil) only for patients with involvement of the circumferential resection margin
  • Short-course preoperative radiotherapy (experimental, n = 674): 25 Gy in five fractions before surgery
People
Sebag-Montefiore D
Local recurrenceHR 0.39 (95% CI 0.27–0.58)Δ 36-month Local recurrence−6.2 pointsDFSHR 0.76 (95% CI 0.62–0.94)Δ 36-month DFS+6 pointsOSHR 0.91 (95% CI 0.73–1.13)
Show the numbers
Results reported for CR07
EndpointAnalysisShort-course preoperative radiotherapyInitial surgery with selective postoperative chemoradiotherapyEffect
Local recurrenceIntention-to-treat analysis including all participants (1350 randomised)Local recurrence (primary outcome measure); rates are at 3 yearsprimarymedian follow-up 4 yearsSebag-Montefiore 20094.4% at 3 y10.6% at 3 yHR 0.39 (95% CI 0.27–0.58)P<0.000199 patients developed local recurrence: 27 in the preoperative radiotherapy group and 72 in the selective postoperative chemoradiotherapy group. The abstract gives an absolute difference at 3 years of 6.2% (95% CI 5.3-7.1). The hazard ratio is for preoperative radiotherapy relative to selective postoperative chemoradiotherapy. As the full text explains (Table 2 footnote), the proportion in the selective postoperative chemoradiotherapy group is calculated by applying the hazard ratio to the proportion in the preoperative radiotherapy group, so the 10.6% is a model-based estimate rather than a value read from the Kaplan-Meier curve.
DFSIntention-to-treat analysis including all participants (1350 randomised)Disease-free survival, a secondary outcome measure; time from randomisation to confirmed local recurrence, distant metastases, or death due to disease or treatmentprimarymedian follow-up 4 yearsSebag-Montefiore 200977.5% at 3 y71.5% at 3 yHR 0.76 (95% CI 0.62–0.94)P=0.013The abstract gives an absolute difference at 3 years of 6.0% (95% CI 5.3-6.8). Secondary outcome measure. The 71.5% in the selective postoperative chemoradiotherapy group is calculated by applying the hazard ratio to the preoperative radiotherapy group's proportion (Table 2 footnote).
OSIntention-to-treat analysis including all participants (1350 randomised)Overall survival, a secondary outcome measure; time from randomisation to death from any causeprimarymedian follow-up 4 yearsSebag-Montefiore 2009——HR 0.91 (95% CI 0.73–1.13)P=0.40330 patients had died: 157 in the preoperative radiotherapy group and 173 in the selective postoperative chemoradiotherapy group. The abstract states that overall survival did not differ between the groups. Secondary outcome measure.
Results reported for CR07
EndpointAnalysisShort-course preoperative radiotherapyInitial surgery with selective postoperative chemoradiotherapyEffect
Local recurrenceIntention-to-treat analysis including all participants (1350 randomised)Local recurrence (primary outcome measure); rates are at 3 yearsprimarymedian follow-up 4 yearsSebag-Montefiore 20094.4% at 3 y10.6% at 3 yHR 0.39 (95% CI 0.27–0.58)P<0.000199 patients developed local recurrence: 27 in the preoperative radiotherapy group and 72 in the selective postoperative chemoradiotherapy group. The abstract gives an absolute difference at 3 years of 6.2% (95% CI 5.3-7.1). The hazard ratio is for preoperative radiotherapy relative to selective postoperative chemoradiotherapy. As the full text explains (Table 2 footnote), the proportion in the selective postoperative chemoradiotherapy group is calculated by applying the hazard ratio to the proportion in the preoperative radiotherapy group, so the 10.6% is a model-based estimate rather than a value read from the Kaplan-Meier curve.
DFSIntention-to-treat analysis including all participants (1350 randomised)Disease-free survival, a secondary outcome measure; time from randomisation to confirmed local recurrence, distant metastases, or death due to disease or treatmentprimarymedian follow-up 4 yearsSebag-Montefiore 200977.5% at 3 y71.5% at 3 yHR 0.76 (95% CI 0.62–0.94)P=0.013The abstract gives an absolute difference at 3 years of 6.0% (95% CI 5.3-6.8). Secondary outcome measure. The 71.5% in the selective postoperative chemoradiotherapy group is calculated by applying the hazard ratio to the preoperative radiotherapy group's proportion (Table 2 footnote).
OSIntention-to-treat analysis including all participants (1350 randomised)Overall survival, a secondary outcome measure; time from randomisation to death from any causeprimarymedian follow-up 4 yearsSebag-Montefiore 2009——HR 0.91 (95% CI 0.73–1.13)P=0.40330 patients had died: 157 in the preoperative radiotherapy group and 173 in the selective postoperative chemoradiotherapy group. The abstract states that overall survival did not differ between the groups. Secondary outcome measure.
Hazard ratio (95% CI) by endpoint. Values below 1 favour the experimental arm.
Local recurrenceDFSOS0.512◀ experimentalcontrol ▶
Data table
EndpointHR95% CI
Local recurrence0.390.27–0.58
DFS0.760.62–0.94
OS0.910.73–1.13
Primary publication: Sebag-Montefiore D, Stephens RJ, Steele R, Monson J, Grieve R, Khanna S, et al. Preoperative radiotherapy versus selective postoperative chemoradiotherapy in patients with rectal cancer (MRC CR07 and NCIC-CTG C016): a multicentre, randomised trial. Lancet. 2009;373(9666):811-20. PubMedDOI

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Sources

  1. Sebag-Montefiore D, Stephens RJ, Steele R, Monson J, Grieve R, Khanna S, et al. Preoperative radiotherapy versus selective postoperative chemoradiotherapy in patients with rectal cancer (MRC CR07 and NCIC-CTG C016): a multicentre, randomised trial. Lancet. 2009;373(9666):811-20.

    PubMedDOI