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

Laura Izquierdo-Sanchez, Angela Lamarca, Adelaida La Casta, Stefan Buettner, Kirsten Utpatel, Heinz Josef Klümpen, Jorge Adeva, Arndt Vogel, Ana Lleo, Luca Fabris, Mariano Ponz-Sarvise, Raffaele Brustia, Vincenzo Cardinale, Chiara Braconi, Gianpaolo Vidili, Nigel B. Jamieson, Rocio IR Macias, Jan Philipp Jonas, Marco Marzioni, Wacław HołówkoTrine Folseraas, Juozas Kupčinskas, Zeno Sparchez, Marcin Krawczyk, Łukasz Krupa, Viorel Scripcariu, Gian Luca Grazi, Ana Landa-Magdalena, Jan N.M. IJzermans, Katja Evert, Joris I. Erdmann, Flora López-López, Anna Saborowski, Alexander Scheiter, Alvaro Santos-Laso, Guido Carpino, Jesper B. Andersen, Jose JG Marin, Domenico Alvaro, Luis Bujanda, Alejandro Forner, Juan W. Valle, Bas Groot Koerkamp, Jesus M. Banales*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

126 Citations (Scopus)
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Background & Aims: Cholangiocarcinoma (CCA) is a rare and heterogeneous biliary cancer, whose incidence and related mortality is increasing. This study investigates the clinical course of CCA and subtypes (intrahepatic [iCCA], perihilar [pCCA], and distal [dCCA]) in a pan-European cohort. Methods: The ENSCCA Registry is a multicenter observational study. Patients were included if they had a histologically proven diagnosis of CCA between 2010-2019. Demographic, histomorphological, biochemical, and clinical studies were performed. Results: Overall, 2,234 patients were enrolled (male/female=1.29). iCCA (n = 1,243) was associated with overweight/obesity and chronic liver diseases involving cirrhosis and/or viral hepatitis; pCCA (n = 592) with primary sclerosing cholangitis; and dCCA (n = 399) with choledocholithiasis. 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, but their concomitant elevation was associated with increased risk of presenting with LAD (odds ratio 2.16; 95% CI 1.43-3.27) or MD (odds ratio 5.88; 95% CI 3.69-9.25). Patients undergoing resection (50.3%) had the best outcomes, particularly with negative-resection margin (R0) (median overall survival [mOS] = 45.1 months); however, margin involvement (R1) (hazard ratio 1.92; 95% CI 1.53-2.41; mOS = 24.7 months) and lymph node invasion (hazard ratio 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%), and 4.0 months for those receiving best supportive care (20.6%). iCCAs were associated with worse outcomes than p/dCCAs. ECOG performance status, MD and CA19-9 were independent prognostic factors. Conclusion: CCA is frequently diagnosed at an advanced stage, a proportion of patients fail to receive cancer-specific therapies, and prognosis remains dismal. Identification of preventable risk factors and implementation of surveillance in high-risk populations are required to decrease cancer-related mortality.

Lay summary: This is, to date, the largest international (pan-European: 26 hospitals and 11 countries) observational study, in which the course of cholangiocarcinoma has been investigated, comparing the 3 subtypes based on the latest International Classification of Diseases 11th Edition (ICD-11) (i.e., intrahepatic [2C12], perihilar [2C18], or distal [2C15] affected bile ducts), which come into effect in 2022. General and tumor-type specific features at diagnosis, risk factors, biomarker accuracy, as well as patient management and outcomes, are presented and compared, outlining the current clinical state of cholangiocarcinoma in Europe.

Original languageEnglish
Pages (from-to)1109-1121
Number of pages13
JournalJournal of Hepatology
Issue number5
Early online date12 Feb 2022
Publication statusPublished - May 2022
EventInternational Liver Congress - London
Duration: 22 Jun 202226 Jun 2022

Bibliographical note

Funding Information: The ENSCCA Registry is competitively funded by the European Association for the Study of the Liver (EASL; Registry grant awards 2016 and 2019) and Incyte Pharma. JMB also received grants from Spanish Carlos III Health Institute (ISCIII) [FIS PI18/01075,PI21/00922 and Miguel Servet Program CPII19/00008), CIBERehd (ISCIII), Department of Health of the Basque Country (2017111010), BIOEF (EiTB Maratoia BIO15/CA/016/BD), “Fundación Científica de la Asociación Española Contra el Cáncer” and the European Union's Horizon 2020 Research and Innovation Program [grant number 825510, ESCALON]. AL also received funding from The Christie Charity. AF received grant support from ISCIII (PI18/00542). CB is recipient of the Lord Kelvin Adam Smith Leadership fellowship at University of Glasgow. ALl was funded by “Fondazione AIRC per la Ricerca sul Cancro” (IG2019 project number 23408). RIRM received grant support from ISCIII (PI20/00189), co-funded ERDF/ESF, "A way to make Europe"/"Investing in your future" and “Centro Internacional sobre el Envejecimiento” (0348_CIE_6_E), Spain. JJGM received grant support from ISCIII (PI19/00819), CIBERehd (ISCIII), “Fundació la Marató de TV3” (201916-31) and Junta de Castilla y León (SA074P20), Spain. NBJ received grant support from Cancer Research UK (grant number A25813).

Publisher Copyright: © 2021 The Authors


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