Prognostic and Predictive Molecular Markers in Cholangiocarcinoma

Abstract

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.

Lenvatinib Plus Programmed Cell Death Protein-1 Inhibitor Beyond First-Line Systemic Therapy in Refractory Advanced Biliary Tract Cancer: A Real-World Retrospective Study in China

“…A total of 98.64% patients developed any-grade AEs and 52.70% developed grade 3/4 AEs. The results were similar to those of recent studies involving a single agent and combined regimens treating refractory advanced BTCs ( 7 , 15 , 18 – 21 ). This combination regimen prolonged the survival duration in both second- and above-line systemic therapies, without significant difference ( p = 0.809).…”

“…Additionally, this study found that 56.75% of the population got a worse ECOG physical score, which partly played a negative role in ensuring patients' compliance. The long-term survival of patients with BTCs was dismal, with 5-year survival rates of 10%-50% (1,21). ABC-01 and ABC-02 clinical trials established the standard of CisGem as a first-line systemic therapy in local advanced and metastatic BTCs (2,22).…”

“…The long-term survival of patients with BTCs was dismal, with 5-year survival rates of 10%–50% ( 1 , 21 ). ABC-01 and ABC-02 clinical trials established the standard of CisGem as a first-line systemic therapy in local advanced and metastatic BTCs ( 2 , 22 ).…”

Body composition is associated with disease aetiology and prognosis in patients undergoing resection of intrahepatic cholangiocarcinoma

“…Recently, next‐generation sequencing revealed molecular subtypes of iCCA that carry prognostic and predictive potential, 27 while the pathological criteria of lymph node and lymphovascular invasion are well‐characterized prognostic factors across European and Asian patient collectives 26,28 . At the same time, patient‐ or host‐centred determinants of prognosis remain relatively unexplored in this rare tumour entity 29 . Accordingly, we investigated tumour aetiology together with body composition in a large, homogenous European cohort of patients undergoing curative‐intent liver resection for iCCA.…”

Adjuvant therapy of biliary tract cancers

“… 44 During gemcitabine chemotherapy, a reduction in CA19-9 equal to or more than 50% correlated with improved therapy response and increased survival but its sensitivity and specificity is 72% and 84%, respectively. 45 Changes in serum CA 19-9 could therefore be used to identify high-risk patients and therefore those who are more likely to benefit from adjuvant therapy. 44 Rather than absolute levels, an observed change may be more applicable but approximately 10% of the general population are Lewis blood group antigen negative and unable to produce CA 19-9.…”