Risk Stratification of Distant Metastasis in Patients Undergoing Adjuvant Chemoradiation for Extrahepatic Bile Duct Cancer

Abstract

Purpose/Objective(s): To analyze the prognostic factors predicting treatment outcome in patients undergoing adjuvant chemoradiation for extrahepatic bile duct cancer. Materials/Methods: Between January 1991 and August 2006, 166 patients with extrahepatic bile duct cancer underwent curative resection followed by adjuvant chemoradiation. There were 120 males and 46 females, and median age was 61 years (range; 34- 86). Postoperative radiotherapy was delivered to tumor bed and regional lymph nodes up to 40-56 Gy. One hundred and fifty-seven patients also received intravenous 5-fluorouracil or oral capecitabine as a radiosensitizer, and 5-fluorouracil-based maintenance chemotherapy was administered to 132 patients. Median follow-up duration was 29 months. Results: The 5-year loco-regional relapse-free, distant metastasis-free, and overall survival rate was 63.5%, 49.4%, and 42.5%, respectively. Major pattern of failure was distant metastasis. There were 51 patients with isolated distant metastases, 21 with isolated loco-regional recurrences, and 25 with combined loco-regional and distant relapses. The most common site of distant failure was the liver (n = 36). On multivariate analysis, hilar tumor, tumor size $2 cm, involved lymph node, and poorly differentiated tumor were associated with inferior distant metastasis-free survival (p = 0.0063, 0.0349, 0.0011, and 0.0184, respectively), whereas patients age, involved resection margin, T stage, and perineural invasion were not (p = 0.5930, 0.2491, 0.7665, and 0.2168, respectively). When patients were divided into four groups based on these risk factors, the 5-year distant metastasis-free survival rates for patients with 0, 1, 2, and 3 risk factors were 86.4%, 57.0%, 31.8%, and 0%, respectively (p\0.0001). Conclusions: Despite the maintenance chemotherapy, distant metastasis was the major pattern of failure in patients undergoing adjuvant chemoradiation for extrahepatic bile duct cancer. More intensified chemotherapy is warranted to improve the treatment outcome of resected extrahepatic bile duct cancer, especially in those with risk factors such as hilar location, larger tumor size, involved lymph node, and/or poorly differentiated histology.