Tumor component proportion determines the prognosis of patients with combined hepatocellular-cholangiocarcinoma
Han Wang1, You-Wen Qian2, Xia Sheng3
1Department of Pathology, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai 200438, China; Department of Pathology, Changhai Hospital, Naval Medical University, Shanghai 200433, China.
Background:
The pathological diagnostic purpose of the tumor component proportion of combined hepatocellular-cholangiocarcinoma (CHC) remains a perplexing issue, hindering clinicians from characterizing its biological behavior and formulating intervention strategies.
Methods:
A multicenter database of patients with CHC who underwent therapeutic hepatectomy was analyzed. Based on a > 70% hepatocellular carcinoma (HCC) or cholangiocarcinoma (CCA) component, the patients were stratified into three groups: CHCHCC-dominant, CHCbalanced, and CHCCCA-dominant. Survival outcomes were assessed using Kaplan-Meier analysis. Tumor markers and recurrence patterns were compared via Chi-square test, and prognostic factors were identified through Cox regression analysis. Postoperative adjuvant transarterial chemoembolization (PA-TACE) benefits were further evaluated.
Results:
Among 19 641 patients with primary liver cancer, 306 with CHC were classified: 93 (30.4%) in the CHCHCC-dominant group, 101 (33.0%) in the CHCbalanced group, and 112 (36.6%) in the CHCCCA-dominant group. The best and the worst prognoses were observed in the CHCHCC-dominant group and CHCCCA-dominant group, respectively (median RFS time: CHCHCC-dominant group 1.02 years, CHCbalanced group 0.36 years, CHCCCA-dominant group 0.30 years; median OS time: CHCHCC-dominant group 3.16 years, CHCbalanced group 1.93 years, CHCCCA-dominant group 1.86 years). The highest ratios of elevated alpha-fetoprotein and carbohydrate antigen 19-9 were recorded in the CHCHCC-dominant group and the CHCCCA-dominant group, respectively. CHCHCC-dominant and CHCCCA-dominant patients showed the most frequent intrahepatic and extrahepatic recurrences, respectively. PA-TACE improved early RFS (< 2 years) only in CHCHCC-dominant patients. Multivariate analysis confirmed that tumor component proportion was an independent prognostic factor for all survival endpoints.
Conclusions:
Predominant HCC or CCA components (> 70% tumor composition) critically shape CHC biology and prognosis. Tumor component proportion emerges as a novel parameter for therapeutic decision-making. We proposed a comprehensive flow chart integrating pathological sampling, histological component evaluation, clinical data mapping, and postoperative intervention strategies for CHC.
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