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 preoperative treatment.2 It is this finding that has, in part, prompted interest in delivering radiotherapy before surgery. The optimal scheduling for preoperative radiotherapy remains unclear. Radiation oncologists in Europe favour a short preoperative approach (25 Gy in five daily fractions), while those in North America and Australia favour a more protracted preoperative regimen (45–50.4 Gy in 25–28 daily fractions, with infusional chemotherapy) given to a more select subgroup of patients with unfavourable clinical features such as tethering and fixation,3 with the aim of "downstaging" the cancer and enhancing operability. While the approach to pelvic radiotherapy may differ, many surgeons advocate that surgery alone, using a total mesorectal excision (TME) technique, could negate the need for pelvic radiotherapy as a result of relatively low pelvic recurrence rates (< 10%).4

This was a large and well-constructed multicentre trial with an adequate sample size and an equal balance of important variables, especially disease stage. The random allocation was simple, and the surgery was standardised by training and supervision of surgeons. Pathological findings were independently reviewed. Importantly, the authors detailed all patients deemed ineligible after randomisation with an acceptable figure of 3% in both arms. All protocol violations were listed. A limited subgroup analysis failed to show a differing treatment effect based on TNM stage or tumour location. The results (overall survival and recurrence) are presented at two years, which is appropriate considering the median follow-up time was only 24.9 months and the number of patients reaching three and four years of follow-up limited at the time of analysis. Short-term toxicity data are presented without any significant difference between the two groups, except for perineal complications. In a subsequent report, the authors showed no difference in postoperative mortality (4% v 3.3%; P = 0.49).5 This is an important finding, as previous studies in which a suboptimal radiotherapy technique was used showed an increased mortality rate.

This is one of the largest studies examining the potential benefits of a short course of preoperative pelvic radiotherapy. Unlike a previous Swedish study,6 this trial failed to show any overall survival benefit (at least at two years), despite a significant reduction in local recurrence from 8.2% to 2.4%. This reduction was seen despite standardised TME. The question remains whether the morbidity (acute and late) of radiotherapy justifies the reduction in local recurrence and its associated morbidity (intractable pain, bleeding, discharge).

Longer-term toxicity data are not yet available from this trial. Nor are data on the late effect of bowel function and quality of life from the addition of radiotherapy. Despite what many would consider an excellent pelvic control rate with TME alone, the local recurrence rate after surgery only in those diagnosed with tumour–node–metastases (TNM) stage III disease was 15%. Pelvic radiotherapy reduced this to 4.3% (P < 0.001). Those with TNM stage II disease also benefited from radiotherapy, although not as much in absolute terms (5.7% v 1%; P = 0.01). Notably, this study included over 500 patients with TNM stage I disease, so it is not surprising that the local recurrence rate in both arms was less than 1%. Patients with TNM stage I disease are not routinely given adjuvant treatment (see TNM classification of malignant tumours7).