Preoperative CRT in patients (pts) with locally advanced rectal cancer downsizes the primary tumor allowing for radical surgery with sphincter preservation in a substantial number of pts. In order to determine whether pts downsized with CRT may be potential candidates for local excision (LE), we investigated the uniformity of the tumor response to, and the pattern of residual disease after, preoperative CRT. Methods: Retrospective analysis of pts with localized T3 or T4 adenocarcinoma of the rectum located within 12cm of the anal verge and treated with neoadjuvant CRT. Results: Two hundred and nineteen pts met the inclusion criteria. Median distance was 5cm from the anal verge. Preoperatively, 193 pts (88%) were staged as T3, 26 pts (12%) as T4 and 97 pts (44%) had clinical N1 disease. Two hundred and thirteen pts had the recommended radical surgery, 6 pts opted for transanal excision. Postoperatively, 43 pts had no evidence of residual tumor in the resected specimen (pathologic complete response (pCR) = 20%). The incidence of nodal disease after CRT in the entire cohort was 20.5%. Overall, T stage was downsized in 64% (140/219) of pts. Similarly, 64% (52/97) of pts with clinical N1 disease had no nodal metastasis at pathologic evaluation (pN0) although 15% of pts with clinical N0 staging were subsequently found to be pN1. The time interval from completion of CRT to surgery was similar between pts with pCR and all other pts (median 49 days vs 48 days respectively). The presence of residual disease in bowel wall, rectal mesentery and nodal basin of the resected specimen was documented. Forty-five pts had no residual tumor in the bowel wall (pT0), however 4 (9%) of these pts had residual extramural disease. Among the 15 pts with pT1 tumors, 3 pts (20%) also had residual disease in the mesentery or nodal basin and in 62 pts with pT2 tumors, 16 pts (26%) had additional residual extramural disease. With a median follow-up of 40 months (range 2-148 months) 182 pts (83%) remain alive and free of disease. Nine pts (4.1%) have experienced a local recurrence. Conclusion: Although overall tumor response rates to CRT within the bowel wall and lymph node basin appears to be similar, 1 in 6 patients downsized to pT0-2 continue to have extramural disease in the rectal mesentery and nodes. LE should be recommended with caution in pts with locally advanced rectal cancer despite substantial reduction in tumor volume with CRT. Better markers are required to identify the pts with pCR who may be eligible for more limited surgical excision.