Liver and Bile
J Hepatol. 2022;76(5):1109–21
Cholangiocarcinoma landscape in Europe: Diagnostic, prognostic and therapeutic insights from the ENSCCA Registry
Background and 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, 2234 patients were enrolled (male/female = 1.29). iCCA (n = 1243) 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 carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9 showed low diagnostic sensitivity, but their concomitant elevation was associated with increased risk of presenting with LAD (odds ratio [OR] = 2.16; 95% confidence interval [CI]: 1.43–3.27) or MD (OR = 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 [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%), and 4.0 months for those receiving best supportive care (20.6%). iCCAs were associated with worse outcomes than p/dCCAs. Eastern Cooperative Oncology Group (ECOG) performance status, MD and CA 19-9 were independent prognostic factors.
Conclusion: Cholangiocarcinoma 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.