Down-staging after two different preoperative chemoradiation schedules in rectal cancer

Aims To compare preoperative downstaging, toxicity and sphincter-saving procedures obtained with preoperative radiotherapy and two different concomitant chemotherapy schedules. Methods From February 1997 to August 2001, 68 consecutive patients were treated with external radiotherapy (5040 cGy in 28 fractions) and concomitant chemotherapy: group a) 36 patients (10T2, 19T3, 7T4, 25 adenocarcinoma and 11 mucinous histology) were treated with cis-diamminedichloroplatinum bolus + 5-fluorouracil continuous infusion; group b) 32 patients (14 T2, 18 T3, 27 adenocarcinoma and 5 mucinous histology) were treated with 5-fluorouracil bolus ± mitomycin C. The interval between the end of radiotherapy and surgery ranged from 4 to 9 weeks. Results Group a) Overall downstaging was 63.9%. Longitudinal shrinkage of the neoplasm allowed conservative surgery in 6 of 11 patients with a pre-chemoradiation tumor location ≤3 cm from the external anal ring. When patients with adenocarcinoma (25/36) were studied separately from patients with mucinous histology, 7/25 patients (28%) were found to have no microscopic evidence of residual tumor (pTO); 8/25 (32%) were found to have only rare isolated cancer cells (pTmic); only 7/25 patients (28%) were found to have no change. Overall, 72% patients had downstaging. In contrast, only 5/11 (45.5%) of mucinous tumors had partial downstaging and 6/11 (54.5%) no downstaging at all. Group b) Overall downstaging was 46.9%. When patients with adenocarcinoma (27/32) were studied separately, 7/27 (26%) were found to have pTO, 3/27 (11.1%) pTmic, and 13/27 (48.1%) no change. Only 1/5 (20%) of mucinous tumors had downstaging and 4/5 (80%) had no downstaging at all. Overall toxicity was comparable among groups a and b, except for lower hematologic and gastrointestinal G3-4 toxicity observed in group a. Conclusions The overall response allowed conservative surgery in 56 (82.3%) of the 68 patients. Continuous infusion of 5-fluorouracil and diamminedichloroplatinum as a radipsensitizer determined better results in group a than group b (63.9% downstaging vs 46.9% even with a higher incidence of mucinous histology). Mucinous histology, for a definitely lower response rate, could benefit from an even more aggressive approach.