In regard to Marijnen et al.: Does radiotherapy compensate for a positive resection margin in rectal cancer patients? IJROBP 2003;55:1311–1320

Abstract

Investigators from the Dutch Colorectal Cancer Group have provided data of great practical importance concerning the efficacy of preoperative radiotherapy in patients with resectable rectal cancer treated with total mesorectal excision (1). In the randomized study conducted by this group, a statistically significant beneficial effect of preoperative irradiation (5 × 5 Gy) has been found in the total number of patients and in the subgroups with a narrow or wide circumferential resection margin (CRM). For the subgroup of patients with positive CRM (defined as equal or less than 1 mm), there was a 7.1% difference in local recurrence between the preoperative irradiation group (9.3%) and up-front surgery group (16.4%), p = 0.08. The authors concluded that the short-term preoperative radiotherapy does not compensate for positive resection margins. However, a type II error (A preoperative radiotherapy in the general population reduces the risk of local recurrence in patients with positive CRM, but this effect has not been detected by statistical tests in the current study) should be considered for several reasons. First, the 7% difference is clinically relevant, p = 0.08 is of borderline significance, and there were 227 patients, which is a rather low number (To detect the 7% difference, approximately 1,200 patients must enter a two-arm randomized study, assuming the test power of 80% and an alpha level of 5%). Second, this is subgroup analysis, which is known to be subject to statistical fluctuations. Third, other data have also shown the lower local recurrence rate for patients with positive margins receiving 5 × 5 Gy preoperative radiotherapy. In the Swedish rectal cancer trial, for patients with positive or questionable margins, the local recurrence rate was 30% (17/57) in the preoperative irradiation arm and 51% (32/62) in the surgery-alone arm (2). These three points, considered together, suggest that short-term preoperative radiotherapy reduces the risk of local failure for CRM-positive patients, although its relative efficacy is lower compared to CRM-negative patients. This is in line with the concept that the effect of preoperative irradiation in rectal cancer depends on the amount of tumor cell deposits to be killed by the radiotherapy (3).