Adjuvant radiotherapy for rectal cancer: recent results, new questions

Many randomised studies have now well established the role of radiotherapy (RT) in rectal cancer: it decreases the rate of local relapse and improves survival for stage II and III. The benefit of RT remains even in case of total mesorectum excision. Preoperative strategy has a better tolerance and is more efficient than post-operative RT. Two schedules have been widely used: an hypofractionated (5 × 5 Gy) and a normofractionated (45-50 Gy by fractions of 1.8-2 Gy) schedule. Both have advantages and drawbacks. Patients with locally advanced tumours or low-lying cancer must benefit from a protracted schedule, which increases down staging and the number of sphincter-preserving surgery. Combined chemoradiotherapy with 5FU or capecitabine enhances local control without a clear benefit in overall survival or disease-free survival. Adjunction of oxaliplatin does not improve the pathological response rate significantly. Results with cetuximab are still disappointing. Bevacizumab seems to increase widely the radiation response, but more data are needed to confirm these preliminary results. With this modern approach, the rate of local relapse is lower than 10%; the main issue is now the occurrence of distant relapses in 25-30% of the patients. Neo-adjuvant chemotherapy (CT) seems the better way to address this issue, because post-operative CT could be done properly in only 50% of the patients. Large prospective trials using neo-adjuvant CT with or without targeted therapies must be designed taking distant relapses and overall survival as main end-points.