Cholangiocarcinoma landscape in Europe: Diagnostic, prognostic and therapeutic insights from the ENSCCA Registry
Authors: 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 Hołówko, Trine Folseraas, Juozas Kupčinskas, Zeno Sparchez, Marcin Krawczyk, Łukasz Krupa, Viorel Scripcariu, Gian Luca Grazi, Ana Landa-Magdalena, Jan NM. 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
Journal: Journal of Hepatology (2022)

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.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.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.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.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.