Management of Locally Advanced or Metastatic Combined Hepatocellular Cholangiocarcinoma

Abstract

Combined hepatocellular cholangiocarcinoma (cHCC-CC) is a rare primary liver malignancy that comprises features of hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC). Due to the rarity of this tumor, the treatment of choice has not yet been defined. For resectable disease, liver resection is the mainstay treatment. However, most patients relapse or display advanced disease and were not surgical candidates. Although the majority of patients are either primarily or secondarily treated in palliative intent, no guideline recommendations or prospective trial reports exist to allow reliable evaluation of debated treatment options. We review different locoregional or medical treatment options for advanced combined hepatocellular cholangiocarcinoma (cHCC-CC) in the neoadjuvant, adjuvant, or palliative setting and discuss the possibility of predictive biomarker-guided therapeutic options.

Treating an Advanced Combined Hepatocellular-Cholangiocarcinoma with a Multikinase Inhibitor

“…cHCC-CC represents a rare type of liver cancer, accounting for less than 5% of all primary liver tumors [1,4]. This malignancy seems to be more common in men, with a mean age at diagnosis of around 64 years old [1,5,6].…”

“…The definition of a combined hepatocellular-cholangiocarcinoma (cHCC-CC) has evolved over the years with the latest definition from the World Health Organization in 2019 describing this rare liver malignancy as a display of biopsy of histomorphological and molecular characteristics of hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC) [1,2]. In Western countries, cHCC-CC comprises 1-5% of all primary liver cancers [1,3]. When deemed feasible, liver surgery with lymph node dissection is considered the standard of care for resectable cases [2].…”

“…When deemed feasible, liver surgery with lymph node dissection is considered the standard of care for resectable cases [2]. Nevertheless, even after surgical resection, tumor recurrence remains high (almost 80% at five years) and the five-year survival rates do not exceed 30% [1]. Furthermore, most patients are often diagnosed at an advanced stage, where surgery is no longer a feasible option [1].…”

“…Nevertheless, even after surgical resection, tumor recurrence remains high (almost 80% at five years) and the five-year survival rates do not exceed 30% [1]. Furthermore, most patients are often diagnosed at an advanced stage, where surgery is no longer a feasible option [1]. Since optimal management of advanced or metastatic cHCC-CC is still unclear, clinicians frequently try to define the dominant phenotype based on radiologic characteristics and the existence of tumor markers like alfafetoprotein (AFP) and carbohydrate antigen 19-9 (CA 19-9) and recommend standard of care for either HCC or CC [1].…”

“…Furthermore, most patients are often diagnosed at an advanced stage, where surgery is no longer a feasible option [1]. Since optimal management of advanced or metastatic cHCC-CC is still unclear, clinicians frequently try to define the dominant phenotype based on radiologic characteristics and the existence of tumor markers like alfafetoprotein (AFP) and carbohydrate antigen 19-9 (CA 19-9) and recommend standard of care for either HCC or CC [1]. If possible, molecular analysis of the tumor should be carried out to identify potentially actionable targets [1].…”