Cholangiocarcinoma landscape in Europe: diagnostic, prognostic and therapeutic insights from the ENSCCA Registry

Izquierdo-Sanchez, L. et al. (2022) Cholangiocarcinoma landscape in Europe: diagnostic, prognostic and therapeutic insights from the ENSCCA Registry. Journal of Hepatology, 76(5), pp. 1109-1121. (doi: 10.1016/j.jhep.2021.12.010) (PMID:35167909)

Abstract

Cholangiocarcinoma (CCA) is a rare and heterogeneous biliary cancer, with increasing incidence and related mortality. This study investigates the clinical course of CCA and subtypes (intrahepatic (iCCA), perihilar (pCCA), and distal (dCCA)) in a pan-European cohort. The ENSCCA Registry is a multicenter observational study. Patients with histologically-proven CCA diagnosis between 2010-2019 were included. Demographic, histomorphological, biochemical, and clinical studies were performed. Overall, 2,234 patients were enrolled (male:female=1.29). iCCA (n=1,243) was associated with overweight/obesity (58.5%) and chronic liver diseases involving cirrhosis (12.6%) and/or viral hepatitis (10.4%); pCCA (n=592) with primary sclerosing cholangitis (8.8%); and dCCA (n=399) with choledocholithiasis (10.3%). At diagnosis, 42.2% of patients had local disease, 29.4% locally-advanced disease (LAD), and 28.4% metastatic disease (MD). Serum CEA and CA19-9 showed low diagnostic sensitivity (69.1% and 40.9% below cutoff, respectively), but their concomitant elevation was associated with increased risk of presenting with LAD [OR=2.16;95%CI:1.43-3.27] or MD [OR=5.88;95%CI:3.69-9.25]. Patients undergoing resection (50.3%) showed the best outcome, particularly with negative-resection margin (R0) [median overall survival (mOS)=45.1 months]; however, margin involvement (R1) [HR=1.92;95%CI:1.53-2.41;mOS=24.7 months] and lymph node invasion [HR=2.13;95%CI:1.55-2.94;mOS=23.3 months] compromised prognosis. Among patients with unresectable disease (49.6%), the mOS was 10.6 months for those receiving active palliative therapies, mostly chemotherapy (26.2%). Patients receiving best supportive care (20.6%) had mOS of 4.0 months, with iCCAs showing worst outcome compared to p/dCCAs. ECOG performance status [HR=1.52;95%CI:1.01-2.31], MD [HR=4.03;95%CI:1.82-8.92] and CA19-9 [HR=2.79;95%CI:1.46-5.33] were independently prognostic for OS. CCA is still diagnosed at advanced stage, a proportion of patients fail to receive cancer-specific therapies, and prognosis is dismal. Identification of preventable risk factors and implementation of surveillance in high-risk populations are required to decrease cancer-related mortality. This is, to date, the largest and more complete international (pan-European: 26 hospitals and 11 countries) observational study, in which the course of CCA is investigated, comparing the three subtypes based on the latest International Classification of Diseases 11 Edition (ICD-11) [i.e., intrahepatic (2C12), perihilar (2C18), or distal (2C15) affected bile ducts] (coming into effect in 2022). General and tumor-type specific features at diagnosis, risk factors, biomarker accuracy, as well as patient management and outcomes, among others, are presented and compared, outlining the current European scenario on the clinical state of CCA.

• Item Type: Articles
• Keywords: Treatment, cholangiocarcinoma, prognosis, risk factors, International Classification of Diseases 11(th) edition (ICD-11), diagnosis, subtypes.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Jamieson, Professor Nigel and Braconi, Professor Chiara
• Authors: Izquierdo-Sanchez, L., Lamarca, A., La Casta, A., Buettner, S., Utpatel, K., Klümpen, H.-J., Adeva, J., Vogel, A., Lleo, A., Fabris, L., Ponz-Sarvise, M., Brustia, R., Cardinale, V., Braconi, C., Vidili, G., Jamieson, N. B., Macias, R. I., Jonas, J. P., Marzioni, M., Hołówko, W., Folseraas, T., Kupčinskas, J., Sparchez, Z., Krawczyk, M., Krupa, Ł., Scripcariu, V., Grazi, G. L., Landa-Magdalena, A., Ijzermans, J. N., Evert, K., Erdmann, J. I., López-López, F., Saborowski, A., Scheiter, A., Santos-Laso, A., Carpino, G., Andersen, J. B., Marin, J. J., Alvaro, D., Bujanda, L., Forner, A., Valle, J. W., Koerkamp, B. G., and Banales, J. M.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences; College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
• Journal Name: Journal of Hepatology
• Publisher: Elsevier
• ISSN: 0168-8278
• ISSN (Online): 1600-0641
• Published Online: 12 February 2022
• Copyright Holders: Copyright © 2021 The Authors
• First Published: First published in Journal of Hepatology 76(5):1109-1121
• Publisher Policy: Reproduced under a Creative Commons licence