Abstract
Background Combined hepatocellular-cholangiocarcinoma (CHC) is a rare and heterogeneous histological subtype of primary liver cancer, which is still poorly understood. This study aimed to describe the epidemiological and clinical features, investigate the prognostic indicators, and develop a competing risk nomogram for CHC. Methods The study cohort was taken from the Surveillance, Epidemiology, and End Results database. The annual percent change (APC) in incidence was calculated using the joinpoint regression. The nomogram was developed based on multivariate competing risk survival analyses and validated by calibration curves. Akaike information criterion, Bayesian information criterion, Harrell's C-index, and area under the receiver operating characteristic curves were obtained to compare prognostic performance. Decision curve analysis was introduced to examine the clinical value of the models. Results The overall incidence of CHC was 0.062 per 100,000 individuals in 2004 and 0.081 per 100,000 individuals in 2018, with an APC of 1.0% (P > 0.05). CHC displayed intermediate clinicopathological features of hepatocellular carcinoma and intrahepatic cholangiocarcinoma. Race, tumor size, vascular invasion, extrahepatic invasion, distant metastasis, grade, surgery, and Metavir stage were confirmed as the independent predictors of cancer-specific survival. The constructed nomogram was well calibrated, which showed better discrimination power and higher net benefits than the current American Joint Committee on Cancer staging system. Patients with liver transplantation had better survival than those with hepatectomy, especially patients within the Milan Criteria (P=0.022 and P=0.015). There was no survival difference between liver transplantation and hepatectomy in patients beyond the Milan Criteria (P=0.340). Conclusion The morbidity of CHC remained stable between 2004 and 2018. The constructed nomogram could predict the prognosis with good performance, which was meaningful to individual treatment strategies optimization. CHC patients should also be considered as potential liver transplantation recipients, especially those within the Milan Criteria, but the finding still needs more evidence to be further confirmed.
Highlights
Combined hepatocellular-cholangiocarcinoma (CHC), defined as primary liver carcinomas with both hepatocellular and cholangiocellular differentiation within the same tumor in the WHO classification of tumors of the digestive system (5th edition), is a rare histological subtype of primary liver cancer (0.4%–14.2%)
Some studies have pointed out the sufficient differences in clinical features and outcomes between CHC and intrahepatic cholangiocarcinomaJournal of Oncology (ICC), indicating that CHC should be considered as a separate entity for a unique staging system [11,12,13,14]
Incidence Trends of Combined HepatocellularCholangiocarcinoma. e overall incidence of CHC remained stable, and it was 0.062 per 100,000 individuals in 2004 and 0.081 per 100,000 individuals in 2018, with an Annual Percent Change (APC) of 1.0% [95% confidence interval (CI) −0.6–2.7, P > 0.05, Figure 1(a)]. en, the study population was divided into two subgroups according to sex. e incidence of CHC in males was 0.086 per 100,000 individuals in 2004 and 0.116
Summary
Combined hepatocellular-cholangiocarcinoma (CHC), defined as primary liver carcinomas with both hepatocellular and cholangiocellular differentiation within the same tumor in the WHO classification of tumors of the digestive system (5th edition), is a rare histological subtype of primary liver cancer (0.4%–14.2%). During the follow-up period, various events, socalled competing risks, may either hinder the observation or modify the occurrence chance of events of interest, including accidents and comorbidities. In this context, conventional survival analyses such as the Kaplan–Meier method and the standard Cox regression model were inappropriate [15]. The second objective of this study was to conduct a competing risk survival analysis and develop a nomogram to predict the prognosis of CHC patients. Combined hepatocellular-cholangiocarcinoma (CHC) is a rare and heterogeneous histological subtype of primary liver cancer, which is still poorly understood. Is study aimed to describe the epidemiological and clinical features, investigate the prognostic indicators, and develop a competing risk nomogram for CHC. CHC patients should be considered as potential liver transplantation recipients, especially those within the Milan Criteria, but the finding still needs more evidence to be further confirmed
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