Risk factors for distant metastasis in extrahepatic bile duct cancer after curative resection (KROG 1814).

Risk factors predicting distant metastasis (DM) in extrahepatic bile duct cancer (EHBDC) patients treated with curative resection were investigated. Medical records of 1418 EHBDC patients undergoing curative resection between Jan 2000 and Dec 2015 from 14 institutions were reviewed. After resection, 924 patients (67.6%) were surveilled without adjuvant therapy, 297 (21.7%) were treated with concurrent chemoradiotherapy (CCRT) and 148 (10.8%) with CCRT followed by chemotherapy. To exclude the treatment effect from innate confounders, patients not treated with adjuvant therapy were evaluated. After a median follow-up of 36.7 months (range, 2.7 - 213.2), the 5-year distant metastasis-free survival (DMFS) rates was 57.7%. On multivariate analysis, perihilar or diffuse tumor (HR 1.391, p=0.004), poorly differentiated histology (HR 2.014, p=0.000), presence of perineural invasion (HR 1.768, p=0.000), positive nodal metastasis (HR 2.670, p=0.000) and preoperative CA 19-9≥37 U/ml (HR 1.353 p=0.000) were significantly associated with inferior DMFS. The DMFS rates significantly differed according to the number of these risk factors. For validation, patients who underwent adjuvant therapy were evaluated. In patients with ≥3 factors, additional chemotherapy after CCRT resulted in a superior DMFS compared with CCRT alone (5-year rate, 47.6% vs 27.7%, p=0.001), but the benefit of additional chemotherapy was not observed in patients with 0-2 risk factors. Tumor location, histologic differentiation, perineural invasion, lymph node metastasis, and preoperative CA 19-9 level predicted DM risk in resected EHBDC. These risk factors might help identifying a subset of patients who could benefit from additional chemotherapy after resection.