Tumor site predicts outcome after radiochemotherapy in squamous-cell carcinoma of the anal region: Long-term results of 101 patients

PURPOSE: This study was designed to assess the long-term results following radiochemotherapy in patients with anal squamous-cell carcinoma and to evaluate the impact of tumor location on response, survival, and colostomy-free survival. PATIENTS AND METHODS: Between 1985 and 2001, a total of 101 patients with anal carcinoma were registered for curative treatment, of whom 77 had involvement of the anal canal alone, 10 cases had extension into the perianal skin, and 14 patients had pure anal margin tumors. Small tumors of the,trial margin were not included since they were treated by surgical excision only. Among the 101 patients were 74 women and 27 men with a median age of 62 (range, 26-84) years. T categories (International Union against Cancer) were T1 (05), T2 (36), T3 (34), and T4 (16). Seventy-one patients had no evidence of nodal disease, whereas 30 presented with involved regional nodes. Radiation treatment was directed to the primary tumor region and to the inguinal, perirectal, and internal iliac nodes using a three-field to four-field box technique with 10 MV photons up to a total dose of 5040 cGy. Lesions greater than 5 cm received an additional boost by interstitial or external radiation depending on circumferential extension of the residual tumor. All patients were scheduled for simultaneous chemotherapy with two cycles of 5-fluorouracil at a dose of 1000 mg/m(2)/day as 120 hours of continuous intravenous infusion on Days I to 5 and 29 to 33 and mitomycin C at 10 mg/m(2)/day on Days I and 29. Median follow-up time was was 7.5 (range, 1-16) years. RESULTS: Overall survival and colostomy-free survival rates for patients with anal canal cancer were 75 percent and 87 percent at five years, respectively. Patients with anal margin cancer had a less favorable outcome with five-year-overall and colostomy-free survival rates of 54 percent and 69 percent, respectively. After correction for imbalance between anal canal and anal margin tumors, i.e., exclusion of TI tumors of the anal canal, difference in overall survival remained significant (73 percent vs. 54 percent, P = 0.01). Following multivariate analysis, tumor location (anal canal vs. anal margin, P = 0.02), age (P = 0.003), and dose intensity of chemotherapy (<= 75 percent vs. > 75 percent, P = 0.03) remained independent significant factors for overall survival. Initial tumor response at six weeks (P = 0.03) was predictive for colostomy-free survival. CONCLUSIONS: With colostomy-free survival rates around 85 percent, long-term treatment results for anal canal carcinoma have reached a satisfactory level. However, patients with larger lesions of the perianal skin are at high risk for locoregional recurrence and possible treatment intensification in this subgroup seems desirable.