Patient Outcomes in Resected Combined Hepatocellular Cholangiocarcinoma (cHCC-ICC) and Intrahepatic Cholangiocarcinoma: A Single Center Study

Background/Objectives: Combined hepatocellular cholangiocarcinoma (cHCC-ICC) is a rare malignancy that involves a combination of features of hepatocellular carcinoma and intrahepatic cholangiocarcinoma (ICC) and exhibits a more aggressive clinical course; however, its risk factors and outcomes remain largely undefined. Methods: This study is a single-center retrospective study of 82 patients diagnosed with ICC or cHCC-ICC who underwent surgical resection from June 2011 to January 2023. Our analysis included 70 patients with resected ICC and 12 with resected cHCC-ICC. Results: The overall survival (OS) for the entire cohort was 21.6 months, with a recurrence-free survival (RFS) of 11.8 months. The cHCC-ICC group had significantly higher levels of AST and ALT (AST median 206 U/L vs. 46 U/L; ALT median 165.5 U/L vs. 48 U/L; p = 0.012 and p = 0.013, respectively), whereas the ICC group had higher alkaline phosphatase (median 66 U/L vs. 104 U/L; p = 0.03). CA 19-9 values (76 U/mL vs. 22 U/mL; p = 0.02) were higher in the ICC group, while AFP values were higher in the cHCC-ICC group (7.3 ng/mL vs. 3.2 ng/mL; p = 0.0004). The cHCC-ICC group had a significantly higher rate of recurrence (83% vs. 47%, p = 0.028) with a significantly decreased RFS (4.7 months vs. 12.4 months; log-rank p = 0.007). In multivariate analysis, patients with resected ICC had a significantly reduced risk of recurrence by 73% compared to their counterparts (HR 0.27 [0.10-0.73], p = 0.01). Conclusions: cHCC-ICC is a rare entity that needs to be further studied to improve patient outcomes. Further studies are warranted and may suggest the need for more aggressive initial treatment strategies in patients diagnosed with cHCC-ICC.