An Expert, Multidisciplinary Perspective on Best Practices in Biomarker Testing in Intrahepatic Cholangiocarcinoma

Abstract

Intrahepatic cholangiocarcinoma (iCCA) is a rare and aggressive malignancy that arises from the intrahepatic biliary tree and is associated with a poor prognosis. Until recently, the treatment landscape of advanced/metastatic iCCA has been limited primarily to chemotherapy. In recent years, the advent of biomarker testing has identified actionable genetic alterations in 40%-50% of patients with iCCA, heralding an era of precision medicine for these patients. Biomarker testing using next-generation sequencing (NGS) has since become increasingly relevant in iCCA; however, several challenges and gaps in standard image-guided liver biopsy and processing have been identified. These include variability in tissue acquisition relating to the imaging modality used for biopsy guidance, the biopsy method used, number of passes, needle choice, specimen preparation methods, the desmoplastic nature of the tumor, as well as the lack of communication among the multidisciplinary team. Recognizing these challenges and the lack of evidence-based guidelines for biomarker testing in iCCA, a multidisciplinary team of experts including interventional oncologists, a gastroenterologist, medical oncologists, and pathologists suggest best practices for optimizing tissue collection and biomarker testing in iCCA.

Diagnosis and treatment of cholangiocarcinoma in Italy: A Delphi consensus statement

“…Irrespective of biopsy sampling method, there was strong (>86%) agreement among the panel for genomic profiling in all patients diagnosed with CCA (statement 11), performed at the time of the initial diagnosis (statement 12), and using NGS technologies (statement 13). These statements are at odds with the 2022 Italian guidelines (Associazione Italiana per lo Studio del Fegato (AISF) et al), but are broadly consistent with the ESMO guidelines (Figure 2) (Mosele et al, 2020;Vogel et al, 2023), 2022 National Comprehensive Cancer Network guidelines (National Comprehensive Cancer Network, 2022), multidisciplinary recommendations from the US (Madoff et al, 2022), and the Italian expert guidelines from FICOG/ISS, which recommend using NGS for genomic profiling of patients with advanced CCA (Pinto et al, 2021). Although the ESMO guidelines do not specifically advocate genomic profiling in every patient diagnosed with CCA, they do recommend genomic profiling prior to any nonsurgical treatment, and particularly for patients with advanced disease prior to systemic treatment (Vogel et al, 2023).…”

Role of Percutaneous Ablation in the Management of Intrahepatic Cholangiocarcinoma

“…iCCA is associated with a poor prognosis and a high mortality rate due to its insidious and aggressive nature, with many patients presenting with locally advanced disease and even metastases, thus limiting therapeutic options [17,18]. Surgical margin-negative resection is considered the only definite treatment, but only about 20% of cases are candidates for surgical treatment [3,19] because of an advanced stage at the time of diagnosis, comorbidities or advanced age [20,21].…”

“…Risk factors associated with iCCA development are cirrhosis, hepatitis B virus (HBV) and hepatitis C virus (HCV), primary sclerosing cholangitis (PSC), hepatolithiasis, hepatobiliary flukes, biliary cirrhosis, gallstones, choledochal cysts, Caroli’s disease, chronic infection by Salmonella typhi or Helicobacter bilis, metabolic syndrome, non-alcoholic steatohepatitis and obesity [ 10 , 11 , 12 , 13 , 14 , 15 ]; however, the majority of iCCA cases are not associated with any risk factors [ 16 ]. iCCA is associated with a poor prognosis and a high mortality rate due to its insidious and aggressive nature, with many patients presenting with locally advanced disease and even metastases, thus limiting therapeutic options [ 17 , 18 ]. Surgical margin-negative resection is considered the only definite treatment, but only about 20% of cases are candidates for surgical treatment [ 3 , 19 ] because of an advanced stage at the time of diagnosis, comorbidities or advanced age [ 20 , 21 ].…”