Pre- versus postoperative radiotherapy in rectal carcinoma: an interim report from a randomized multicentre trial

Abstract

Since October 1980 a randomized multicentre trial has been in progress among patients with rectal carcinoma, in whom high-dose fractionated pre-operative irradiation (total dose 25.5 Gy in 5-7 days) is being tested against postoperative irradiation to a high dose level using a conventional fractionation scheme (totally 60 Gy in 8 weeks) delivered only to a high-risk group of patients (Dukes' stages B and C). The primary aim of the trial is to investigate whether local recurrence rate differs between the two groups, and a secondary aim is to see whether 5-year survival will differ between the two groups of patients. Up to October 1984, 360 patients have been randomly allocated to these two groups. Locally curative surgery has been performed in 161 patients in the pre-operative irradiation group and in 152 patients in the postoperative irradiation group. Pre-operative irradiation was extremely well tolerated and there were no irradiation-related complications; 95 per cent of these patients received their treatment according to the intended schedule. However, 48 of the 161 patients had a tumour in Dukes' stage A. Pre-operative radiotherapy had no impact on postoperative mortality or the occurrence of anastomosis dehiscence, but significantly more patients with perineal wound sepsis after an abdominoperineal resection were found in the group of patients receiving pre-operative radiotherapy. This prolonged the stay in hospital after surgery. Postoperative radiotherapy was not so well tolerated as pre-operative treatment, and in a substantial number of patients the treatment could not be commenced until a relatively long time after surgery. To date, the local recurrence rate is acceptably low (approximately 10 per cent) in both treatment groups.

Radiotherapy in Addition to Radical Surgery in Rectal Cancer

“…Between 12-27% of the patients did not receive the planned postoperative dose (26,(28)(29)(30), whereas this occurred in less than 10% in the groups of patients randomized to preoperative radiotherapy (19)(20)(21)(22)(23)(24)(25). This difference in acute toxicity was seen also in the trial contrasting a preoperative approach to a postoperative one (37).…”

“…The extent of this problem is not possible to evaluate in postoperative trials since only those with an uneventful postoperative period and in shape for randomization within the stipulated time period, e.g., 4-6 weeks, will be included. The only trial that can evaluate how often patients are not in shape for initiating the postoperative radiotherapy within a certain time period is the Uppsala trial (37) in which patients were randomized prior to surgery. It was then found that the radiotherapy could be started within 6 weeks in only 54% of the patients.…”

“…An increased frequency of perineal wound sepsis after abdominoperineal resection was found in some trials (24,37,38). In these trials, the hospital stay is usually slightly longer, about 3-5 days on an average, in preoperatively irradiated patients.…”

“…No influence on postoperative mortality was noticed although no upper age limit was applied. Preoperative radiotherapy at a high dose can thus be delivered without augmenting postoperative mortality (37). It is expected that a large volume, irradiated at a high dose, should be deleterious, at least in elderly patients.…”

Perioperative Radiotherapy in the Management of Rectal Cancer

“…As shown in Table 1, which displays all controlled, randomized trials, when the same dose was used, the effect on the local recurrence rate was far better with preoperative radiotherapy than with postoperative radiotherapy. The question of timing -pre-or postoperative therapy -has been addressed in only one randomized trial in which patients were allocated to preoperative or postoperative radiotherapy (29,30). In that trial, the Uppsala trial, preoperative radiotherapy was superior to postoperative irradiation in reducing local recurrence rates.…”