Does preoperative radiotherapy improve outcome in patients with resectable rectal cancer?

Design: Multicentre international randomised controlled trial. Setting: 108 hospitals, with a predominance of hospitals in Holland. Patients: 1805 eligible patients with histologically proven adenocarcinoma of the rectum. Patients with fixed tumours were excluded. All patients had either a low anterior resection or an abdominoperineal resection using the standardised surgical approach of total mesorectal excision (TME). Intervention: After stratification for treatment centre and anticipated type of operation, 897 patients were assigned to receive, or not receive, preoperative short course pelvic radiotherapy (25 Gy in five daily fractions). Main outcome measures: Overall survival and local recurrence at 2 years; overall and distant recurrence at 2 years; and postoperative mortality and morbidity (operative blood loss and perineal complications). Overall survival was analysed on an intention-to-treat basis and included all eligible patients. The rate of local recurrence was calculated for patients in whom macroscopically complete resection had been achieved. The rate of distant recurrence was calculated for patients who did not have distant disease at the time of surgery. Main results: Median follow-up in surviving eligible patients without local recurrence was 24.9 months (range, 1.1–56 months). There was no difference in overall survival between the two groups (82.0% radiotherapy and surgery v 81.8% surgery alone; P = 0.84). However, local recurrence was significantly lower in patients who had received radiotherapy compared with those who had not (2.4% v 8.2%; P < 0.001). There was no difference in the rate of distant recurrence (P = 0.87). Median operative blood loss was marginally increased in the combined arm (1000 v 900 mL; P < 0.001), as were perineal complications after abdominoperineal resection (26% v 18%; P = 0.05). Conclusion: A short course of preoperative pelvic radiotherapy reduces pelvic recurrence after total mesorectal excision. Despite this, overall survival was not improved. The primary treatment for rectal cancer is surgery. The rationale for also irradiating the pelvis is to prevent the suffering associated with local recurrence, even if survival is not improved. Pelvic recurrence after surgery occurs in 20%–50% of patients with poor pathological features, such as transmural spread and nodal involvement. 1 Adjuvant treatment may be delivered either before or after surgery and may also include chemotherapy. The risk of serious late bowel complications after postoperative adjuvant treatment is reported to be higher when compared with preop-erative treatment. 2 It is this finding that has, in part, prompted interest in delivering radiotherapy before surgery. The optimal scheduling …