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

To compare preoperative down-staging, toxicity and sphincter-saving procedures obtained with preoperative radiotherapy and two different concomitant chemotherapy schedules.

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.

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.

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.