Pancreatic Invasion in Distal Cholangiocarcinoma Is a Poor Prognostic Factor: A New Approach Integrating Tumor Depth of Invasion

BACKGROUND: The 8th edition of the American Joint Committee on Cancer (AJCC) staging system for distal cholangiocarcinoma (dCCA) uses depth of invasion (DOI) for T classification; however, it does not consider invasion into adjacent organs such as the pancreas. We investigated the prognostic significance of DOI and pancreatic invasion in patients with dCCA. METHODS: We retrospectively analyzed 130 patients with dCCA who underwent pancreatoduodenectomy between 2003 and 2016. The optimal DOI cutoff for predicting overall survival (OS) was determined using time-dependent receiver operating characteristic analysis. Associations between clinicopathological factors, pancreatic invasion, and prognosis were evaluated using Kaplan-Meier survival analysis and Cox proportional hazards models. RESULTS: The optimal DOI cutoff for OS was 4 mm. Patients with DOI > 4 mm had significantly poorer survival than those with DOI ≤ 4 mm (p < 0.0001). Pancreatic invasion was associated with worse prognosis (p < 0.001) and was more prevalent in tumors with greater DOI. Among patients with DOI > 4 mm, pancreatic invasion significantly worsened OS (p < 0.05), whereas no prognostic impact was observed in patients with DOI ≤ 4 mm. Multivariate analysis identified the combination of DOI > 4 mm and pancreatic invasion, lymph node metastasis, histological type, and positive resection margin as independent adverse prognostic factors. A novel classification incorporating DOI, pancreatic invasion, and lymph node status provided improved prognostic stratification. CONCLUSION: The combination of DOI > 4 mm and pancreatic invasion is an independent predictor of poor prognosis in dCCA. Incorporating pancreatic invasion into DOI-based classification may improve prognostic assessment beyond the current AJCC staging system.