Squamous-cell carcinoma of the anal canal: Predictors of treatment outcome

PURPOSE: The incidence of anal canal squamous-cell carcinoma is increasing. Limited data exist on predictors of treatment failure. This study was designed to identify predictors for relapse/persistence after first-line therapy. METHODS: Using one database, we identified 131 Stages I-III patients treated for primary anal canal squamous-cell carcinoma at our institution from December 1986 to August 2006, with minimum six-month follow-up. Demographic, pathologic, treatment, and outcome data were extracted. Treatment failure was defined as biopsy-proven persistence or relapse (local and/or distant). Univariate, bivariate, and multivariate survival analyses were performed. RESULTS: Of 131 patients (median age, 58.3 years; median follow-up, 2.9 (range, 0.6-11.2) years), 66 percent were females, 43.5 percent were Stage II, and 11 (8 percent) were HIV-positive. Surgery only (local excision) was uncommon (6.9 percent, n=9). One hundred twenty-two patients (93.1 percent) received radiotherapy; two required preradiotherapy diversion. Although 114 (93.4 percent) completed radiotherapy, most required treatment breaks, making total duration of radiotherapy longer than planned. Almost all patients undergoing radiotherapy (96.7 percent, 118/122) also had chemotherapy: 118 (100 percent, Stages I-III) had concurrent chemotherapy: (98 (83.8 percent) mitomycin/5-fluorouracil, 12 (10.2 percent) cisplatin/5-fluorouracil, 8 (6.8 percent) 5-fluorouracil alone); 35 of 46 (76 percent) Stage III patients received induction chemotherapy (34 (97.1 percent) cisplatin/5-fluorouracil, 1 (2.8 percent) 5-fluorouracil alone). Many (44 percent Stages I/II, 48.9 percent Stage III) required dose adjustments. Thirty-seven patients (28.2 percent) failed first-line therapy. There were no differences between patients with relapse (n=22) or persistence (n=15) of disease. Bivariate analyses demonstrated that T stage (P=0.0019), completion of radiotherapy, and total radiotherapy dose (P=0.03) were all significantly associated with treatment failure. On multivariate analyses, disease stage (P=0.05) and completion of radiotherapy (P=0.01) remained significant predictors of relapse-free survival. CONCLUSIONS: Tolerance of chemoradiation seems to be an important predictor of treatment success. Effective therapies with less acute toxicity must be identified.