Current Updates on Diagnosis and Management of Cholangiocarcinoma: from Surgery to Targeted Therapy

Haryanto Surya, Murdani Abdullah, Erni Juwita Nelwan, Ari Fahrial Syam, Ignatius Bima Prasetya, Benedictus Stefanus, Cleopas Martin Rumende, Hamzah Shatri


Cholangiocarcinoma is commonly described as any malignancy arising from the lining of the bile duct and is recognized as one of the most common biliary malignancies. We conducted a literature review of current available evidences and guidelines.
Based on the anatomical location of the origin of the mass, cholangiocarcinoma can be divided into intrahepatic, perihilar, and distal cholangiocarcinoma. Each of these subtypes has their own risk factors, best treatment options, and prognosis. The most common risk factors for cholangiocarcinoma also differs based on geography and population backgrounds. Histopathological biopsy remained the gold standard for cholangiocarcinoma diagnosis, however various advances has been made in diagnostic procedure, including MRCP, EUS, ERCP, EBUS, and cholangioscopy. Surgical resection is still the best treatment modality for cholangiocarcinoma, but it can only be done in few patients considering most patients were diagnosed in the unresectable state. Other treatment options includes conventional chemotherapy, locoregional therapy, systemic targeted therapy, and palliative best supportive care. Cholangiocarcinoma has an abundance of molecular targets and advances in biomolecular technologies bring further hope for future curative treatment options. Treatment options should be chosen individually based on each patient’s condition and setting.
Cholangiocarcinoma is still a major health problem in hepatobiliary malignancies. Multiple options are available for cholangiocarcinoma treatments.


cholangocarcinoma; surgery; diagnosis; therapy


Bowlus CL, Arrive L, Bergquist A, et al. AASLD practice guidance on primary sclerosing cholangitis and cholangiocarcinoma. Hepatology. 2022 Sep 9.

Bridgewater J, Galle PR, Khan SA, et al. Guidelines for the diagnosis and management of intrahepatic cholangiocarcinoma. J Hepatol. 2014;60(6):1268-89.

Uppal DS, Wang AY. Advances in endoscopic retrograde cholangiopancreatography for the treatment of cholangiocarcinoma. World J Gastrointest Endosc. 2015;7(7):675-87.

Khan AS, Dageforde LA. Cholangiocarcinoma. Surg Clin North Am. 2019;99(2):315-35.

Vogel A, Bridgewater J, Edeline J, et al. Biliary tract cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol. 2022 Nov 10.

Bertuccio P, Malvezzi M, Carioli G, et al. Global trends in mortality from intrahepatic and extrahepatic cholangiocarcinoma. J Hepatol. 2019;71(1):104-14.

Palmer WC, Patel T. Are common factors involved in the pathogenesis of primary liver cancers? A meta-analysis of risk factors for intrahepatic cholangiocarcinoma. J Hepatol. 2012;57(1):69-76.

Khan SA, Tavolari S, Brandi G. Cholangiocarcinoma: Epidemiology and risk factors. Liver Int. 2019;39 Suppl 1:19-31.

Prueksapanich P, Piyachaturawat P, Aumpansub P, Ridtitid W, Chaiteerakij R, Rerknimitr R. Liver fluke-associated biliary tract cancer. Gut Liver. 2018;12(3):236-45.

Saluja SS, Sharma R, Pal S, Sahni P, Chattopadhyay TK. Differentiation between benign and malignant hilar obstructions using laboratory and radiological investigations: a prospective study. HPB (Oxford). 2007;9(5):373-82.

Iavarone M, Piscaglia F, Vavassori S, et al. Contrast enhanced CT-scan to diagnose intrahepatic cholangiocarcinoma in patients with cirrhosis. J Hepatol. 2013;58(6):1188-93.

Lamarca A, Ross P, Wasan HS, et al. Advanced Intrahepatic Cholangiocarcinoma: Post Hoc Analysis of the ABC-01, -02, and -03 Clinical Trials. J Natl Cancer Inst. 2020;112(2):200-10.

Inchingolo R, Acquafredda F, Posa A, et al. Endobiliary biopsy. World J Gastrointest Endosc. 2022;14(5):291-301.

Nakazawa T, Naitoh I, Hayashi K. Usefulness of Intraductal Ultrasonography in the Diagnosis of Cholangiocarcinoma and IgG4-Related Sclerosing Cholangitis. Clin Endosc. 2012;45(3):331-6.

Yodice M, Choma J, Tadros M. The Expansion of Cholangioscopy: Established and Investigational Uses of SpyGlass in Biliary and Pancreatic Disorders. Diagnostics (Basel). 2020;10(3).

Ayoub F, Yang D, Draganov PV. Cholangioscopy in the digital era. Transl Gastroenterol Hepatol. 2018;3:82.

Patel AH, Harnois DM, Klee GG, LaRusso NF, Gores GJ. The utility of CA 19-9 in the diagnoses of cholangiocarcinoma in patients without primary sclerosing cholangitis. Am J Gastroenterol. 2000;95(1):204-7.

de Jong MC, Nathan H, Sotiropoulos GC, et al. Intrahepatic cholangiocarcinoma: an international multi-institutional analysis of prognostic factors and lymph node assessment. J Clin Oncol. 2011;29(23):3140-5.

Hyder O, Marques H, Pulitano C, et al. A nomogram to predict long-term survival after resection for intrahepatic cholangiocarcinoma: an Eastern and Western experience. JAMA Surg. 2014;149(5):432-8.

Farges O, Regimbeau JM, Fuks D, et al. Multicentre European study of preoperative biliary drainage for hilar cholangiocarcinoma. Br J Surg. 2013;100(2):274-83.

Jarnagin WR, Fong Y, DeMatteo RP, et al. Staging, resectability, and outcome in 225 patients with hilar cholangiocarcinoma. Ann Surg. 2001;234(4):507-17; 17-9.

Heimbach JK, Gores GJ, Haddock MG, et al. Liver transplantation for unresectable perihilar cholangiocarcinoma. Semin Liver Dis. 2004;24(2):201-7.

Shroff RT, Kennedy EB, Bachini M, et al. Adjuvant Therapy for Resected Biliary Tract Cancer: ASCO Clinical Practice Guideline. J Clin Oncol. 2019;37(12):1015-27.

Ikeda M, Nakachi K, Konishi M, et al. Adjuvant S-1 versus observation in curatively resected biliary tract cancer: a phase III trial (JCOG1202:ASCOT). Journal of Clinical Oncology. 2022;40(4suppl):382-2.

Valle J, Wasan H, Palmer DH, et al. Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer. N Engl J Med. 2010;362(14):1273-81.

Okusaka T, Nakachi K, Fukutomi A, et al. Gemcitabine alone or in combination with cisplatin in patients with biliary tract cancer: a comparative multicentre study in Japan. Br J Cancer. 2010;103(4):469-74.

Oh D, He AR, Qin S, et al. Updated overall survival (OS) from the phase III TOPAZ-1 study of durvalumab (D) or placebo (PBO) plus gemcitabine and cisplatin (+ GC) in patients (pts) with advanced biliary tract cancer (BTC). Annals of Oncology. 2022;33(suppl7): S19-S26. 10.1016/annonc/annonc1036.

Abou-Alfa GK, Macarulla T, Javle MM, et al. Ivosidenib in IDH1-mutant, chemotherapy-refractory cholangiocarcinoma (ClarIDHy): a multicentre, randomised, double-blind, placebo-controlled, phase 3 study. Lancet Oncol. 2020 Jun;21(6):796-807.

Zhu AX, Macarulla T, Javle MM, et al. Final overall survival efficacy results of Ivosidenib for patients with advanced cholangiocarcinoma with IDH1 mutation: The phase 3 randomized clinical ClarIDHy trial. JAMA Oncol. 2021;7(11):1669-77.

Abou-Alfa GK, Sahai V, Hollebecque A, et al. Pemigatinib for previously treated, locally advanced or metastatic cholangiocarcinoma: a multicentre, open-label, phase 2 study. Lancet Oncol. 2020;21(5):671-84.

Javle M, Roychowdhury S, Kelley RK, et al. Infigratinib (BGJ398) in previously treated patients with advanced or metastatic cholangiocarcinoma with FGFR2 fusions or rearrangements: mature results from a multicentre, open-label, single-arm, phase 2 study. Lancet Gastroenterol Hepatol. 2021;6(10):803-15.

Javle M, Borad MJ, Azad NS, et al. Pertuzumab and trastuzumab for HER2-positive, metastatic biliary tract cancer (MyPathway): a multicentre, open-label, phase 2a, multiple basket study. Lancet Oncol. 2021;22(9):1290-300.

Chawla SP, Wong S, Quon D, et al. Three year results of Blessed: Expanded access for DeltaRex-G for an intermediate size population with advanced pancreatic cancer and sarcoma (NCT04091295) and individual patient use of DeltaRex-G for solid malignancies (IND# 19130). Front. Mol. Med. 2022;2:1092286. doi: 10.3389/fmmed.2022.1092286

Liu S, Chawla SP, Bruckner H, et al. Long Term Survival Following DeltaRex-G/DeltaVax Tumor-Targeted Gene Therapy for Advanced Chemotherapy-Resistant Malignancies: An Academic Milestone. Clin Oncol. 2021;6:1807.

Park YJ, Kang DH. Endoscopic drainage in patients with inoperable hilar cholangiocarcinoma. Korean J Intern Med. 2013;28(1):8-18.

Bambha K, Kim WR, Talwalkar J, et al. Incidence, clinical spectrum, and outcomes of primary sclerosing cholangitis in a United States community. Gastroenterology. 2003;125:1364–9.

Barner‐Rasmussen N, Pukkala E, Jussila A, Farkkila M. Epidemiology, risk of malignancy and patient survival in primary sclerosing cholangitis: a population‐based study in Finland. Scand J Gastroenterol. 2020;55:74–81.

Lindkvist B, Benito de Valle M, Gullberg B, Björnsson E. Incidence and prevalence of primary sclerosing cholangitis in a defined adult population in Sweden. Hepatology. 2010;52:571–7.

Kaplan GG, Laupland KB, Butzner D, Urbanski SJ, Lee SS. The burden of large and small duct primary sclerosing cholangitis in adults and children: a population‐based analysis. Am J Gastroenterol. 2007;102:1042–9.

Toy E, Balasubramanian S, Selmi C, Li CS, Bowlus CL. The prevalence, incidence and natural history of primary sclerosing cholangitis in an ethnically diverse population. BMC Gastroenterol. 2011;11:83.

Boberg KM, Aadland E, Jahnsen J, Raknerud N, Stiris M, Bell H. Incidence and prevalence of primary biliary cirrhosis, primary sclerosing cholangitis, and autoimmune hepatitis in a Norwegian population. Scand J Gastroenterol. 1998;33:99–103.

Molodecky NA, Kareemi H, Parab R, et al. Incidence of primary sclerosing cholangitis: a systematic review and meta‐analysis. Hepatology. 2011;53:1590–9.

Bandyopadhyay D, Bandyopadhyay S, Ghosh P, et al. Extraintestinal manifestations in inflammatory bowel disease: prevalence and predictors in Indian patients. Indian J Gastroenterol. 2015;34:387–94.

Bowlus CL, Li CS, Karlsen TH, Lie BA, Selmi C. Primary sclerosing cholangitis in genetically diverse populations listed for liver transplantation: unique clinical and human leukocyte antigen associations. Liver Transpl. 2010;16:1324–30.

Koczka CP, Geraldino‐Pardilla LB, Lawlor G. Primary sclerosing cholangitis and its relationship to the colon in a Black cohort of inflammatory bowel disease patients. J Clin Gastroenterol. 2014;48:e19–21.

Kuo A, Gomel R, Safer R, Lindor KD, Everson GT, Bowlus CL. Characteristics and outcomes reported by patients with primary sclerosing cholangitis through an online registry. Clin Gastroenterol Hepatol. 2019;17:1372–8.

Broomé U, Glaumann H, Hellers G, Nilsson B, Sörstad J, Hultcrantz R. Liver disease in ulcerative colitis: an epidemiological and follow up study in the county of Stockholm. Gut. 1994;35:84–9.

Fraga M, Fournier N, Safroneeva E, et al. Primary sclerosing cholangitis in the Swiss Inflammatory Bowel Disease Cohort Study: prevalence, risk factors, and long‐term follow‐up. Eur J Gastroenterol Hepatol. 2017;29:91–7.

Guerra I, Bujanda L, Castro J, et al. Clinical characteristics, associated malignancies and management of primary sclerosing cholangitis in inflammatory bowel disease patients: a multicentre retrospective cohort study. J Crohns Colitis. 2019;13:1492–500.

Lakatos L, Pandur T, David G, et al. Association of extraintestinal manifestations of inflammatory bowel disease in a province of western Hungary with disease phenotype: results of a 25‐year follow‐up study. World J Gastroenterol. 2003;9:2300–7.

Olsson R, Danielsson A, Järnerot G, et al. Prevalence of primary sclerosing cholangitis in patients with ulcerative colitis. Gastroenterology. 1991;100:1319–23.

Parlak E, Kosar Y, Ulker A, Dagli U, Alkim C, Sahin B. Primary sclerosing cholangitis in patients with inflammatory bowel disease in Turkey. J Clin Gastroenterol. 2001;33:299–301.

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