This is a randomized Phase II trial investigating the optimal timing of delivery of neoadjuvant therapy, in order to maximize the proportion of patients with distal rectal cancer who may be cured while preserving the rectum. Patients with distal rectal cancer who are candidates for a coloanal anastomosis or abdominoperineal excision will be randomized to receive neoadjuvant chemotherapy before (induction arm) or after (consolidation arm) chemoradiation. Patients will be restaged 4 to 6 weeks after completing all neoadjuvant therapy. Those with incomplete tumor response will undergo a total mesorectal excision. Patients with complete tumor response will be observed, and will have a total mesorectal excision only if they develop signs of tumor relapse during follow-up.
The treatment of rectal cancer with neoadjuvant chemoradiation, total mesorectal excision, and postoperative adjuvant chemotherapy results in excellent local tumor control. However, many patients still die as a consequence of distant metastasis. In addition, long-term survivors have diminished quality of life, due primarily to removal of the rectum. This study aims to increase survival by optimizing the use of neoadjuvant chemotherapy, and to improve quality of life by preserving the rectum in patients with a sustained clinical response to neoadjuvant therapy.