ArticlesRandomised trial of surgery alone versus radiotherapy followed by surgery for potentially operable locally advanced rectal cancer*
Introduction
Rectal cancer is one of the most common malignant diseases with 11 500 cases diagnosed in the UK in 1994 alone. Little change has been seen in survival rates, which remain at about 40% at 5 years from diagnosis. In an attempt to increase the rate of curative resection and hence survival, several trials have investigated the role of preoperative radiotherapy in treatment of rectal cancer. The first UK Medical Research Council (MRC) trial of preoperative radiotherapy for rectal cancer was a three-arm randomised trial with 824 patients comparing a control (surgery alone) group with a group treated with 20 Gy given in 10 equal fractions and another treated with a single exposure of 5 Gy.1 These doses of radiation were chosen after trials by the Veterans Administration Surgical Adjuvant Group2 and the Princess Margaret Hospital, Toronto,3 suggested survival advantage with radiotherapy for patients with tumours of Dukes' stage C. Despite the suggestion of a real biological effect of the radiotherapy in the first MRC trial, with significant changes in tumour stage, no advantage was found for either radiotherapy group over the control group in terms of disease recurrence or survival. However, the trial did demonstrate the importance of fixity as a prognostic factor—80% of mobile tumours had apparently curative resections compared with 50% of partially fixed, and 30% of fixed tumours. The importance of fixity was reflected in the survival pattern; 5-year survival for fixed or partially fixed tumours was just 29% compared with 48% for mobile tumours.
In 1981, the MRC began this trial of a higher dose of preoperative radiotherapy in patients with fixed or partially fixed tumours of the rectum who were thought to be suitable for abdominoperineal excision or anterior restorative resection. The aim was to increase the number of patients in whom curative resection could be done, and so improve survival rates. The dose of radiation (40 Gy in 20 fractions over 4 weeks) was chosen as the highest that was deemed safe before anterior resection with the wide-field technique proposed. We present the results of this trial with a minimum follow-up time for surviving patients of 5 years.
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Patients and methods
Eligible patients were men or women younger than 80 years who; had histologically proven adenocarcinoma of the rectum partially or totally fixed within the pelvis with the lower margin of the tumour within 15 cm of the anal verge; were deemed suitable and fit for the proposed treatment and available for regular follow-up; were free of disseminated disease (confirmed by clinical and radiological examination); and had had no previous malignant disease. We gained local ethics committee approval
Results
Recruitment into the trial started in November, 1981, and ended in November, 1989, when 279 patients had been enrolled; 140 patients were allocated surgery alone and 139 preoperative radiotherapy (figure 1). Recruitment, initially steady, declined after publication, and perhaps misinterpretation, of the disappointing results of the first MRC trial of low-dose radiotherapy. After 7 years of accrual, only slightly more than half the required number of patients had been entered. We decided to
Discussion
The extended follow-up period of the study enabled us to come close to achieving our objectives despite failure to enrol the 450 patients required for the trial design. The effects of radiotherapy on recurrence of cancer and survival are similar to the estimates on which the trial design was based. Failure to recruit the planned number of patients is reflected in the wide 95% CI seen for each of the main endpoints.
There was evidence of benefit from preoperative radiotherapy before the trial.4, 5
References (14)
- et al.
Effect of preoperative irradiation on resectability of colorectal carcinoma
Int JRadiat OncolBiolPhys
(1982) The evaluation of low dose preoperative X-ray therapy in the management of operable rectal cancer; results of a randomly controlled trial
Br J Surg
(1984)- et al.
Preoperative irradiation for carcinoma of the rectum and rectosigmoid colon: report of a National Veterans administration randomised study
Cancer
(1975) - et al.
Preoperative irradiation in operable cancer of the rectum: report of the Toronto trial
Can J Surg
(1977) - et al.
Preoperative irradiation for unresectable rectal and rectosigmoid carcinomas
Cancer
(1983) - et al.
Preoperative irradiation with high-dose fractionation in ade no carcinoma of the rectum and rectosigmoid
Ada Radiol Oncol
(1982) - et al.
Resection of ‘inoperable’ rectal cancer following radiotherapy
Br J Surg
(1985)
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Writing committee and participating surgeons listed at end of article