Aims: To compare preoperative down-staging, 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 (10 T2, 19 T3, 7 T4, 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 down-staging was 63.9%. Longitudinal shrinkage of the neoplasm allowed conservative surgery in 6 of 11 patients with a pre-chemoradiation tumor location < or = 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 (pT0); 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 down-staging. In contrast, only 5/11 (45.5%) of mucinous tumors had partial down-staging and 6/11 (54.5%) no down-staging at all. Group b) Overall down-staging was 46.9%. When patients with adenocarcinoma (27/32) were studied separately, 7/27 (26%) were found to have pT0, 3/27 (11.1%) pTmic, and 13/27 (48.1%) no change. Only 1/5 (20%) of mucinous tumors had down-staging and 4/5 (80%) had no down-staging 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 radiosensitizer determined better results in group a than group b (63.9% down-staging 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.