Liquid Biopsy Shows Potential in Cholangiocarcinoma Care
Cholangiocarcinoma (CCA), an aggressive and often fatal cancer of the bile ducts, remains one of the most difficult hepatobiliary malignancies to diagnose and monitor. A recent review in the World Journal of Gastroenterology highlights the transformative potential of liquid biopsy (LB) as a noninvasive tool for improving early detection, prognosis, and personalized care in CCA. The findings could have significant implications for clinicians in the United States, where early detection of CCA remains limited and mortality rates are rising.
Study Findings: Liquid Biopsy Offers Comprehensive Tumor Profiling
The review emphasizes that LB enables detection of circulating tumor DNA (ctDNA), cell-free DNA (cfDNA), RNA, and extracellular vesicles from blood or bile—eliminating the need for repeated tissue biopsies. This approach provides a comprehensive molecular snapshot of the tumor’s heterogeneity across primary and metastatic sites, allowing clinicians to monitor disease evolution in real time.
Advanced sequencing methods, including next-generation sequencing (NGS) and methylation-based assays, improve sensitivity by identifying low-frequency and epigenetic alterations. The authors cite a comparative analysis in which bile cfDNA identified cancer driver mutations in 54% of biliary tract cancer cases versus 17% with plasma cfDNA, underscoring the superior diagnostic performance of bile-based sampling.
Despite its promise, the review cautions that low ctDNA concentrations in early-stage disease and the lack of standardized protocols remain key challenges. Current data are primarily derived from small, single-institution studies, underscoring the urgent need for multicenter validation and harmonization of LB methodologies before widespread clinical adoption.
Clinical Implications: A New Era of Precision Oncology
Liquid biopsy holds the potential to revolutionize CCA management by enabling noninvasive, repeatable testing for diagnosis, risk stratification, and treatment optimization, the authors stated. By capturing tumor evolution over time, LB supports precision oncology approaches that personalize therapy based on molecular signatures and resistance patterns.
When integrated with radiomics, multiomics databases, and artificial intelligence (AI), LB could further improve predictive modeling and early detection, particularly in patients with primary sclerosing cholangitis at risk for CCA. Standardized LB implementation may also reduce procedural risks and long-term costs associated with repeated tissue biopsies.
As research accelerates, LB could soon become a cornerstone of CCA management—enabling earlier detection, personalized treatment, and real-time monitoring. While not yet ready to replace tissue biopsy, its integration into future clinical algorithms could significantly advance outcomes in this challenging malignancy, the review authors concluded.
Reference:
Kotsifa E, Saffioti F, Mavroeidis VK, et al. Cholangiocarcinoma: The era of liquid biopsy. World J Gastroenterol. 2025;31(11):104170. doi:10.3748/wjg.v31.i11.104170
