PREOPERATIVE CHEMORADIATION FOR EXTRAPERITONEAL T3 RECTAL-CANCER - ACUTE TOXICITY, TUMOR RESPONSE, AND SPHINCTER PRESERVATION

Purpose: To evaluate whether or not an intermediate dose of preoperati ve external radiation therapy intensified by systemic chemotherapy cou ld improve the tumor response, sphincter preservation, and tumor contr ol. Methods and Materials: Between March 1990 and December 1995, 83 co nsecutive patients with resectable extraperitoneal adenocarcinoma of t he rectum were treated with preoperative chemoradiation: bolus i.v. mi tomycin C (MMC), 10 mg/m(2), Day 1 plus 24-h continuous infusion i.v. 5-fluorouracil (5FU) 1000 mg/m(2), Days 1-4, and concurrent external b eam radiotherapy (37.8 Gy). All but 2 patients had T3 disease. Surgery was performed 4-6 weeks after the end of chemoradiation. Results: Tot al Grade 3-4 acute toxicity during chemoradiation was observed in 11 ( 13%) patients: hematological Grade 3 toxicity was recorded in 8 (10%) patients, and Grade 4 toxicity was recorded in 2 (2%) patients. Grade 3 diarrhea was seen in 2 (2%) patients. No patient had major skin or u rological acute toxicity. Two patients had no surgery: 1 died before s urgery from septic complications after Grade 1 hematological toxicity; 1 refused surgery and is still alive after 6 years. There was no post operative mortality and the overall perioperative morbidity rate was 2 5%. The analysis of tumor response involved 81 patients. Overall, 9% ( 7) of 81 patients had a complete pathologic response. Comparing the st age at the diagnostic workup with the pathologic stage, tumor downstag ing was observed in 46 (57%) patients. We had 7 (9%) pTO, 5 (6%) pT1, 33 (41%) pT2, and 36 (44%) pT3. Nodal status downstaging was detected in 46 patients (57%). No evidence of nodal involvement was observed in 59 patients (73%). The incidence of tumor response was affected signi ficantly by the number of quarters of rectal circumference involved (p = 0.03) and, marginally, by the length of the tumor (p = 0.09). The d istance between the lower pole of the tumor and the anorectal ring had no influence. Of the patients, 63 (78%) had a sphincter-saving surgic al procedure. In 12 (44%) of 27 patients candidate for an APR, the sph incter was preserved, as it was in 19 (95%) of 20 probable candidates. Lengthening of the distance between the anorectal ring and the lower pole of the tumor > 20 mm was observed in 21 patients (26%). Of 63 pat ients, 4 (6%) had moderate soilage after the sphincter-saving procedur e. Conclusion: Preoperative combined modality therapy seems to afford some potential advantages in nonrandomized trials: patients are able t o tolerate higher chemotherapy doses and they experience a lower acute toxicity. Tumor downstaging and resectability rates are high; sphinct er preservation is feasible. Larger T3 tumors remained less influenced by this treatment; thus, taking into account the low toxicity rate re corded, a more aggressive schedule should be applied in these resectab le tumors. (C) 1998 Elsevier Science Inc.