Abstract
Simple SummaryCholangiocarcinoma (CCA) is a heterogenous and aggressive malignancy of the intra- and extrahepatic biliary tract, marked by a steeply rising incidence on a global scale. While surgery remains the only curative treatment option, most patients present with advanced or unresectable disease, and are, therefore, treated with systemic therapy, albeit with limited benefit. Biomarkers obtained from either the patients’ serum or tumor tissue might facilitate therapy guidance by selecting patients who would benefit the most from surgical and adjuvant treatment strategies, as well as by identifying those with higher risk of disease recurrence. Furthermore, several genetic aberrations in CCA have been linked with improved response upon targeted therapies, thus highlighting their role as predictive biomarkers. In this review we provide an overview of currently known prognostic and predictive biomarkers and discuss their role in CCA.Cholangiocarcinoma (CCA) is the second most common primary liver cancer and subsumes a heterogeneous group of malignant tumors arising from the intra- or extrahepatic biliary tract epithelium. A rising mortality from CCA has been reported worldwide during the last decade, despite significant improvement of surgical and palliative treatment. Over 50% of CCAs originate from proximal extrahepatic bile ducts and constitute the most common CCA entity in the Western world. Clinicopathological characteristics such as lymph node status and poor differentiation remain the best-studied, but imperfect prognostic factors. The identification of prognostic molecular markers as an adjunct to traditional staging systems may not only facilitate the selection of patients who would benefit the most from surgical, adjuvant or palliative treatment strategies, but may also be helpful in defining the aggressiveness of the disease and identifying patients at high-risk for tumor recurrence. The purpose of this review is to provide an overview of currently known molecular prognostic and predictive markers and their role in CCA.
Highlights
Cholangiocarcinoma (CCA) is a highly aggressive malignancy and the second most common primary liver tumor, accounting for three percent of all gastrointestinal malignancies [1]
Since a combination of two prognostic markers may improve the power of prognosis, the ratio of certain serum proteins with high diagnostic and predictive power was applied in several cancer types
Circulating tumor cells (CTC), various metabolites found in bile, blood, or urine, as well as extracellular vesicles represent some of other biomarkers currently evaluated for diagnosis and outcome prediction in patients with CCA [69]
Summary
Cholangiocarcinoma (CCA) is a highly aggressive malignancy and the second most common primary liver tumor, accounting for three percent of all gastrointestinal malignancies [1]. Advancements in organ preservation and poor survival outcomes following surgical resection have promoted consideration of liver transplantation (LT) as a curative approach for patients suffering from pCCA and iCCA [18,19]. A French multicenter randomized, intent-to-treat study (NCT02232932) comparing the 5-year survival following capecitabine-based chemoradiotherapy with subsequent LT to standard liver resection in patients suffering pCCA is ongoing [21]. Results from a multicenter, single-arm, prospective study (NCT02878473) evaluating the 5-year survival in patients with single iCC ≤ 2 cm in size, liver cirrhosis, and CA 19-9 ≤ 100 ng/mL, undergoing LT are eagerly awaited. The identification of preoperatively available molecular markers of prognosis as an adjunct to traditional staging systems has emerged as a promising strategy to select patients who may benefit the most from surgical and adjuvant therapy. The identification of predictive markers might result in precise and effective systemic treatment
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