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Abstract
Purpose: Risk factors predicting distant metastasis (DM) in extrahepatic bile duct cancer (EHBDC) patients treated with curative resection were investigated.

Materials and methods: Medical records of 1,418 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.

Results: After a median follow-up of 36.7 months (range, 2.7 to 213.2 months), the 5-year distant metastasis-free survival (DMFS) rate was 57.7%. On multivariate analysis, perihilar or diffuse tumor (hazard ratio [HR], 1.391; p=0.004), poorly differentiated histology (HR, 2.014; p < 0.001), presence of perineural invasion (HR, 1.768; p < 0.001), positive nodal metastasis (HR, 2.670; p < 0.001) and preoperative carbohydrate antigen (CA) 19-9 ≥ 37 U/mL (HR, 1.353; p < 0.001) 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.

Conclusion: 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.

Affiliations

Younghee Park 1, Tae Hyun Kim 2, Kyubo Kim 1, Jeong Il Yu 3, Wonguen Jung 1, Jinsil Seong 4, Woo Chul Kim 5, Jin Hwa Choi 6, Ah Ram Chang 7, Bae Kwon Jeong 8, Byoung Hyuck Kim 9, Tae Gyu Kim 10, Jin Hee Kim 11, Hae Jin Park 12, Hyun Soo Shin 13, Jung Ho Im 13, Eui Kyu Chie 14
1Department of Radiation Oncology, Ewha Womans University College of Medicine, Seoul, Korea.
2Center for Proton Therapy, National Cancer Center, Goyang, Korea.
3Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
4Department of Radiation Oncology, Yonsei University College of Medicine, Seoul, Korea.
5Department of Radiation Oncology, Inha University School of Medicine, Incheon, Korea.
6Department of Radiation Oncology, Chung-Ang University College of Medicine, Seoul, Korea.
7Department of Radiation Oncology, Soonchunhyang University Seoul Hospital, Soonchunhyang University College of Medicine, Seoul, Korea.
8Department of Radiation Oncology, Gyeongsang National University College of Medicine, Jinju, Korea.
9Department of Radiation Oncology, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, Korea.
10Department of Radiation Oncology, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, Korea.
11Department of Radiation Oncology, Keimyung University School of Medicine, Daegu, Korea.
12Department of Radiation Oncology, Hanyang University College of Medicine, Seoul, Korea.
13Department of Radiation Oncology, CHA University School of Medicine, Seongnam, Korea.
14Department of Radiation Oncology, Seoul National University College of Medicine, Seoul, Korea.