Cancer Res Treat.  2024 Jan;56(1):272-279. 10.4143/crt.2023.616.

Risk Factors for Distant Metastasis in Extrahepatic Bile Duct Cancer after Curative Resection (KROG 1814)

• Park Y
• Kim TH
• Kim K
• Yu JI
• Jung W
• Seong J
• Kim WC
• Choi JH
• Chang AR
• Jeong BK
• Kim BH
• Kim TG
• Kim JH
• Park HJ
• Shin HS
• Im JH
• Chie EK

• KMID: 2550342
• DOI: http://doi.org/10.4143/crt.2023.616

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.

Keyword

Extrahepatic bile duct cancer; Distant metastasis; Risk factors

Figure

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  Fig. 1. Flow diagram of patient selection. CCRT, concurrent chemoradiotherapy; EHBDC, Extrahepatic bile duct cancer; RT, radiotherapy.

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  Fig. 2. Kaplan-Meier curves for overall, locoregional recurrence-free, and distant metastasis-free survival in patients undergoing surgery alone.

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  Fig. 3. Kaplan-Meier curves for distant metastasis-free survival according to the number of risk factors in patients undergoing surgery alone.

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  Fig. 4. Kaplan-Meier curves for distant metastasis-free survival according to the receipt of chemotherapy after concurrent chemoradiotherapy (CCRT) in patients with 0-2 risk factors (A) and 3-5 risk factors (B).

Reference

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