Phase II clinical trial of preoperative combined chemoradiation for T3 andT4 resectable rectal cancer - Preliminary results

PURPOSE: Although preoperative chemoradiation for high-risk rectal cancer m ay improve survival and local recurrence rate, its adverse effects are not well defined. This prospective study evaluated the use of preoperative chem oradiation for T3 and T4 resectable rectal cancer, with special emphasis on treatment morbidity, pathologic remission rate, quality of life, and anore ctal function. METHODS: Forty-two patients (30 men, 12 women) were enrolled in the study. Median distance of the distal tumor margin from the anal ver ge was 6.5 cm. Preoperative staging was based on digital rectal examination , endorectal ultrasound, and Computed tomography. None of the patients had distant metastases. All patients had 45 Gy (1.8 Gy/day in 25 fractions) ove r five weeks, plus 5-fluorouracil (350 mg/m(2)/day) and leucovorin (20 mg/m (2)/day) bolus on days 1 to 5 and 29 to 33. Quality of life was assessed wi th the European Organization for Research and Treatment of Cancer 30-item q uality-of-life questionnaire (QLQ-C30) and its colorectal cancer-specific m odule (QLQ-CR38) questionnaires. Objective anorectal function was assessed by anorectal manometry and pudendal nerve terminal motor latency. Surgery w as performed 46 (range, 24-63) days after completion of adjuvant therapy. R ESULTS: Nineteen patients (45 percent) had Grade 3 or 4 chemoradiation-indu ced toxic reactions. Four patients developed intercurrent distant metastase s or intraperitoneal carcinomatosis at completion of chemoradiation. Thirty -eight patients underwent surgical resection: abdominoperineal resection, a nterior resection, and Hartmann's procedure were performed in 55 percent, 3 9 percent (11 of 15 patients had a diverting stoma), and 5 percent, respect ively. Major surgical complications occurred in 7 patients (18 percent) and included anastomotic leak (n = 1), pelvic abscess (n = 1), small-bowel obs truction (n = 3), and wound breakdown (n = 2). Final pathology was Stage 0 (no residual disease), I, II, and III in 6 (16 percent), 7 (18 percent), 9 (24 percent), and 16 (42 percent) patients, respectively. There was a deter ioration, after chemoradiation and surgery, in the quality of life on all s ubscales assessed, with physical, role, and social function being most seve rely affected. The symptoms most adversely affected were micturition, defec ation, and gastrointestinal problems. Body image and sexual enjoyment deter iorated in both men and women. Chemoradiation alone led to prolonged pudend al nerve terminal motor latency in 57 percent of 7 patients assessed. CONCL USION: Preliminary results have identified defined costs with preoperative chemoradiation, which included treatment-induced toxicity, a high stoma rat e, and adverse effects on quality of life and anorectal function.