Optimization of Diagnosis and Biomarker Testing in Intrahepatic Cholangiocarcinoma

June/July 2022, Vol 3, No 2

Although biomarker testing may improve access to personalized treatment options for patients with cholangiocarcinoma (CCA), barriers exist to the adoption of precision medicine, requiring consideration of best practices and current gaps in standard practices, a recent review article suggests.1

For patients with CCA, biomarker testing has contributed to a new treatment paradigm; however, barriers to precision medicine implementation include delays in diagnosis, challenges in tissue acquisition, ineffective collaboration of the multidisciplinary team involved in patient management, and a lack of awareness regarding the importance of biomarker testing.2-6 Because metastatic CCA progresses rapidly, improvements in diagnosis, biomarker testing, and therapeutic options are needed.

The purpose of the review article was to summarize the discussion between the University of California, Davis and University of California, Irvine multidisciplinary hepatobiliary teams regarding best practices for intrahepatic CCA (iCCA) diagnosis, tissue acquisition, communication among academic and community healthcare teams, and education improvements.

Potential Challenges to and Solutions for Optimal Diagnosis and Biomarker Testing

Barriers to a timely diagnosis of iCCA identified in the article included patients presenting with vague or nonspecific symptoms and the absence of specific histologic iCCA markers and other histologic features to aid in diagnosis. Cited best practices for diagnosis included the use of albumin in situ hybridization to differentiate iCCA from liver metastases, the use of techniques that identify cholangiolar pattern, and improved awareness of imaging characteristics associated with iCCA.

The article identified the following barriers to iCCA biopsy and tissue collection: lack of standardized imaging modalities and tissue acquisition methods, lack of availability or use of rapid on-site evaluation, difficult tumor locations, and lack of feedback between pathologists and interventional radiologists. Best practices noted for biopsy and tissue collection included defining the standards for biopsy collection, including parameters regarding which lesion to biopsy, number and length of cores to collect, and information regarding specimen handling, biopsy technique, and tissue preservation efforts; providing a clear rationale and goals for biomarker analysis; and improving communication and feedback between pathologists and interventional radiologists.

The authors suggested the following best practices for multidisciplinary teams to optimize iCCA patient outcomes: establishing formal channels of communication among team members, identifying who is responsible for ordering next-generation sequencing, determining a leadership structure, and conducting regular meetings and molecular tumor boards to discuss biomarker test results.

Recommended strategies to improve knowledge and utilization of biomarker testing in patients with iCCA included enhancing physicians’ knowledge of the advantages and disadvantages of each biomarker test and result interpretation, developing guidelines and recommendations for integration of biomarker testing in iCCA management, improving communication between academic and community-based radiologists, and developing iCCA-specific multidisciplinary focus groups to enhance knowledge of the importance of biomarker testing.


Overall recommendations from the authors included the following: (1) Train academic and community physicians on the importance of next-generation sequencing in iCCA for precision-based treatment. (2) Educate clinicians on the need for next-generation sequencing for inclusion of patients in biomarker-driven clinical trials. (3) Disseminate information related to approved treatments, available clinical trials, and new techniques to improve biopsy collection.

The authors highlighted the importance of biomarker testing into multidisciplinary care of patients with iCCA, ideally at diagnosis. They also underscored the need for academic and community colleagues to work together to overcome challenges in the care of patients with iCCA.


  1. Cho MT, Gholami S, Gui D, et al. Optimizing the diagnosis and biomarker testing for patients with intrahepatic cholangiocarcinoma: a multidisciplinary approach. Cancers (Basel). 2022;14:392.
  2. Bibeau K, Bachini M, Lindley A, et al. Exploring the diagnostic journey and life impact of patients with cholangiocarcinoma (CCA): results from a large patient survey in the United States. J Clin Oncol. 2021;39(suppl_3):277.
  3. Lamarca A, Kapacee Z, Breeze M, et al. Molecular profiling in daily clinical practice: practicalities in advanced cholangiocarcinoma and other biliary tract cancers. J Clin Med. 2020;9:2854.
  4. Nakamura Y, Taniguchi H, Ikeda M, et al. Clinical utility of circulating tumor DNA sequencing in advanced gastrointestinal cancer: SCRUM-Japan GI-SCREEN and GOZILA studies. Nat Med. 2020;26:1859-1864.
  5. Tomlins SA, Hovelson DH, Suga JM, et al. Real-world performance of a comprehensive genomic profiling test optimized for small tumor samples. JCO Precis Oncol. 2021;5:1312-1324.
  6. Parikh K, Cameron DR, Abair T, et al. Targeted therapies in cholangiocarcinoma: assessment of US oncologist practice patterns. J Clin Oncol. 2021;39(suppl_3):347.

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