Tumor budding may be a promising prognostic indicator in intrahepatic cholangiocarcinoma: A multicenter retrospective study

PURPOSE: This retrospective study evaluated our hypothesis that high tumor budding (≥10 buds) may help determine the appropriate T category for more accurate staging of intrahepatic cholangiocarcinoma (ICC). METHODS: We analyzed the clinical and histopathologic data of 235 consecutive patients with histologically confirmed ICC following hepatectomy at five university hospitals in the Kansai region of Japan between January 2009 and December 2020. ICC staging was based on the Liver Cancer Study Group of Japan (LCSGJ) staging system, 6th edition. RESULTS: Patients with ICC with high budding showed significantly shorter disease‐specific survival (DSS) and disease‐free survival (DFS) than patients with low/intermediate budding. Cox proportional hazards regression analysis showed a hazard ratio of 2.2‐2.3 (P < 0.05) for high budding. Based on these results, we modified the T category of ICC in the LCSGJ staging system by adding severity of tumor budding as a fourth determinant. This proposed staging system for ICC has significantly improved the prognostic accuracy for both DSS and DFS (both: P < 0.05). CONCLUSIONS: High tumor budding is a new candidate for an additional determinant of the T category in staging ICC. An LCSGJ staging system containing an additional evaluation of tumor budding may lead to improved staging accuracy.