Preoperative combined modality therapy for clinically resectable uT3 rectal adenocarcinoma.

PURPOSE: To determine the acute toxicity, outcome, and sphincter preservation rates in patients with clinically resectable uT3 adenocarcinoma of the rectum treated with preoperative combined modality therapy. METHODS AND MATERIALS: A total of 72 patients were treated from 12/90-7/98 with preoperative 50.4 Gy plus 2 cycles of concurrent 5-fluorouracil (5-FU) and leucovorin (LV) bolus daily x 5 followed by sharp or total mesorectal excision and 4 cycles of postoperative 5-FU and LV. RESULTS: Individual Grade 3+ toxicities during preoperative therapy included diarrhea, 11%; bowel movements, 9%; leukopenia, 18%; tenesmus, 1%; and thrombocytopenia, 1%. Total Grade 3+ toxicity was 28%. The pathologic complete response (CR) rate was 13%, and an additional 9% had a clinical CR for a total CR rate of 22%. Of the 35 patients who were judged clinically by their operating surgeon to require an abdominoperineal resection (APR) and were therefore treated with the goal of sphincter preservation, 89% were able to undergo sphincter-preserving surgery. Of the 21 patients eligible for analysis, 81% had good to excellent sphincter function. The 3-year actuarial patterns of failure were 2% local, 8% abdominal, and 13% distant. The 3-year actuarial survival was 95%. CONCLUSIONS: Our data confirm our preliminary reports of encouraging rates of acute toxicity, local control, survival, sphincter preservation and function with preoperative combined modality therapy. It is an alternative approach for the treatment of uT3 clinically resectable rectal cancer.

30 Gy may be an adequate dose in patients with anal cancer treated with excisional biopsy followed by combined-modality therapy.

BACKGROUND AND OBJECTIVES: There are a subset of patients with invasive anal cancers who undergo an excisional biopsy either before or after combined-modality therapy (CMT). The objective of this study is to determine whether these patients can be adequately treated with a lower dose of pelvic radiation therapy. METHODS: A total of 25 patients were treated with CMT either before or after an excisional biopsy. The four subsets included 8 patients with initial excision followed by CMT with 30-34 Gy (EX/30), 6 patients with initial excision followed by CMT with 45-50.4 Gy (EX/45), 10 patients treated by CMT with 30 Gy followed by an excision (30/EX), and 1 patient by CMT with 45 Gy followed by an excision (45/EX). RESULTS: For the total group, the actuarial 5-year disease-free survival was 78%, overall survival was 86%, colostomy-free survival was 91%, and local control was 82%. When patients received CMT either before or following an excision, the actuarial local control and survival results with 30-34 Gy vs. 45-50.4 Gy were similar. In contrast to radiation dose, in patients who received 30-34 Gy, the sequence of the excision (before or after CMT) did appear to have a borderline significant impact on local control. Actuarial 5-year local control was 100% for EX/30 vs. 67% for 30/EX (P = 0.08). CONCLUSIONS: Because of the small number of patients in each group and the retrospective nature of the analysis, it is difficult to draw definitive conclusions from this study. However, our data suggest that in patients who are selected to undergo an initial excisional biopsy followed by CMT, 30 Gy may be an adequate radiation dose. Local control may be higher in patients who undergo an excisional biopsy followed by CMT compared with the converse.

Sphincter preservation in rectal cancer with preoperative radiation therapy and coloanal anastomosis: long term follow-up.

BACKGROUND: To determine if preoperative radiation therapy allows sphincter preservation in the treatment of rectal cancer. METHODS: Thirty six patients with the diagnosis of invasive, resectable, primary adenocarcinoma of the rectum limited to the pelvis were enrolled on a Phase I/II trial of preoperative radiation therapy plus low anterior resection/coloanal anastomosis. By preoperative assessment, all patients had invasive tumors (5,T2; 31,T3) involving the distal half of the rectum and clinically required an abdominoperineal resection. The median tumor size was 3.8 cm [range: 1.5-7 cm] and the median distance from the anal verge was 4 cm [range: 3-7 cm]. The whole pelvis received 46.80 Gy followed by a 3.60 Gy boost to the primary tumor bed. The median follow-up was 56 months [range: 4-121 months]. RESULTS: Of the 35 patients who underwent resection, 5 (14%) had a complete pathologic response and 27 (77%) were able to successfully undergo a low anterior resection/coloanal anastomosis. The incidence of local failure was crude: 17% and 5-year actuarial: 21%. The 5-year actuarial survival was 64%. Analysis of sphincter function using a previously published scale was performed at the time of last follow-up in the 27 patients who underwent a low anterior resection/coloanal anastomosis. Function was good or excellent in 85%. The median number of bowel movements/day was 2 (range: 0-8). CONCLUSIONS: Our data suggest that preoperative radiation therapy allows sphincter preservation in 77% of selected patients who would otherwise require an abdominoperineal resection, and 85% have good to excellent sphincter function. Given the moderate local failure rate, we now routinely use preoperative combined modality therapy plus postoperative chemotherapy for patients with clinical T3 disease.