Long-Term Survival of Combined Hepatocellular-Cholangiocarcinoma: A Nationwide Study

Abstract

Background. Combined hepatocellular-cholangiocarcinoma (HCC-CC) is an aggressive primary liver cancer. However, the clinical features are not clearly understood due to limited literature and the complex nature of both hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC). Methods. The records of 100,754 patients with newly diagnosed liver cancer between 2004 and 2013 were obtained from the Taiwan Cancer Registry. The primary outcome measures were overall survival and local recurrence-free survival. The median follow-up time was 60 months (29-120 months). Results. HCC-CC tended to share some characteristics with HCC, including increased frequency of stage I cases, high individual tumor rates, and similar patterns of viral hepatitis B and hepatitis C infections. In contrast, HCC-CC showed malignant behavior similar to that of CC, as high-grade tumor cell differentiation and presentation of jaundice was predominant in HCC-CC and CC compared to HCC. Overall survival and local recurrence-free survival rates of HCC-CC were between HCC and CC rates. The mortality rate of HCC-CC was 79.2% (HCC: 77.5%, CC: 93.5%) and the local recurrence rate of HCC-CC was 65.3% (HCC: 74.6%, CC: 88.4%). Surgical treatment was an independent factor for the longterm prognosis of HCC-CC, while trans-arterial chemoembolization (TAcE) promoted survival in both surgical and non-surgical groups. Conclusions. Our data confirmed that, although it reflects the malignant behavior of CC, HCC-CC should mainly be characterized as a subtype of HCC. With careful selection of patients, curative resection and TACE might benefit the survival of patients with HCC-CC. The Oncologist 2021;9999:• • Implications for Practice: Combined hepatocellular-cholangiocarcinoma (HCC-CC) is a rare cancer that shares demographic characteristics, as well as survival probabilities, with both hepatocellular carcinoma and cholangiocarcinoma. It occurs frequently in patients with HBV infection, cirrhotic liver background and early stage. Compared to 20% of initial resection rates of its counterparts, HCC-CC has higher initial resection rate (55%). Although short-term overall survival is inferior to HCC, its long-term overall survival is similar with HCC.

Anatomical liver resection improves surgical outcomes for combined hepatocellular-cholangiocarcinoma: A propensity score matched study

“…In our study, the clinicopathological features of cHCC-CCA were more similar to those of patients suffering from HCC infected with HBV (hepatitis B virus), both of which are associated with elevated AFP levels in most patients. The results of this study are consistent with those of previous studies ( 15 , 21 ). In clinical settings, cHCC-CCA is often misdiagnosed as either HCC or iCCA via imaging or hematology tests due to non-specific clinical manifestations, and a confirmed diagnosis of cHCC-CCA usually requires surgical resection ( 22 ).…”

“…Although cHCC-CCA has features of both HCC and CC, several studies have observed that cHCC-CCA shares more etiological features with HCC than with iCCA, especially with respect to its epithelial characteristics ( 5 , 15 ). In our study, the clinicopathological features of cHCC-CCA were more similar to those of patients suffering from HCC infected with HBV (hepatitis B virus), both of which are associated with elevated AFP levels in most patients.…”

“…A nationwide study in China has indicated that although cHCC-CCA reflects the malignant behavior of iCCA, it should be characterized as a subtype of HCC due to similarities in mortality rates and long-term surgical outcomes between HCC and cHCC-CCA ( 15 ). The superiority of anatomical resection (AR) over non-anatomical resection (NAR) for surgical outcomes in HCC patients is an ongoing controversy.…”

Prognostic analysis of patients with combined hepatocellular-cholangiocarcinoma after radical resection: A retrospective multicenter cohort study

“…TACE is a common adjuvant therapy after HCC, and previous studies have shown that TACE prolongs OS and RFS in HCC patients[ 35 ], which is based on the rationale of hindering the rich blood supply of HCC, thus promoting tumor necrosis[ 36 ]. TACE treatment has also been linked to improved survival in patients with cHCC-CCA following radical surgery, according to recent researches[ 24 , 25 ]. Studies including patients with unresectable cHCC-CCA have also shown that cHCC-CCA lesions with a rich blood supply have a higher response rate and better treatment outcomes for TACE[ 37 ].…”

Efficacy of dual checkpoint inhibitors in a patient with a mixed hepatocellular cholangiocarcinoma

“…Due to its molecular profile and genetic similarities, it is frequently considered a distinct form of cholangiocarcinoma,9 10 and it is often treated according to biliary tract cancer guidelines 11. In contrast, findings from a substantial cohort study using the Taiwan national Cancer Registry have demonstrated that managing this condition as HCC leads to more favourable treatment results, underscoring the distinctive complexities associated with CHC 12…”