Should preoperative or postoperative therapy be administered in the management of rectal cancer?

Combined-modality therapy consisting of surgery, radiation, and chemotherapy with 5-fluorouracil is the recommended management for patients with stage II and III rectal cancer. The place of radiation therapy as part of this combined modality treatment for localized rectal cancer will be reviewed, and some of the novel chemoradiation combinations under investigation will be highlighted. Currently, there are two sequencing approaches for the adjuvant administration of pelvic radiation therapy. The first is surgical resection and, if the tumor is stage T(3-4) and/or N(1-2), adjuvant postoperative chemoradiation and further chemotherapy. The second approach for patients with ultrasound T(3-4) or clinical T(4) disease is preoperative therapy followed by surgical resection and postoperative chemotherapy. The adjuvant radiation management approach in the United States and Europe has been shifting toward preoperative therapy to promote sphincter-preserving surgery and decrease acute and late bowel toxicity. The recently published 5-year results of the randomized German CAO/ARO/AIO 94 trial of preoperative versus postoperative chemoradiation support a standard preoperative treatment approach. Preoperative chemoradiation therapy also allows for the investigation of innovative agents (capecitabine, oxaliplatin, irinotecan, bevacizumab, and cetuximab) in combination with pelvic radiation. These new combinations may have the potential to further increase the therapeutic benefit of neoadjuvant therapy.