43Unexpected Burden of Cholangiocarcinoma in a Prospective Population-Based Cohort in Gipuzkoa Province (Spain: 2010-2024)
Elide Gutierrez, Jone Narbaiza, Adelaida La Casta, Ana Landa-Magdalena, Tania Pastor, Beatriz Val, Ainhoa Lapitz, lratxe Taixe, loana Riano, Pedro M Rodrigues, Maria J Perugorria, Raul Jimenez-Aguero, Luis Bujanda, Laura Izquierdo-Sanchez, Jesus M BanalesAbstract
Background
Cholangiocarcinoma (CCA) is a rare and aggressive malignancy of the bile ducts with a poor prognosis. Although its incidence and mortality are increasing, the true burden of disease is likely underestimated due to underdiagnosis and limitations in coding systems. Population-based studies describing subtype-specific (ICD-11) epidemiology, clinical characteristics, and outcomes remain scarce and are urgently needed. This study aimed to characterize real-world CCA incidence, treatment patterns, and survival in Gipuzkoa, Spain.
Methods
All CCA patients at Donostia University Hospital, the central referral center for CCA in Gipuzkoa, were included (2010-2024). Clinical, treatment, and outcome data were collected. Population based age-standardized incidence (ASIR) and mortality rates (ASMR) were calculated. ctDNA and germline DNA from 147 patients underwent whole-exome sequencing.
Results
A total of 727 patients were included, 79.2% with histological confirmation. Median age was 72 years, 65% male. lntrahepatic CCA (iCCA) was most frequent (48%), followed by distal (dCCA, 30%} and perihilar (pCCA, 21 %). ASIR rose during the retrospective period (0.63-4.16) and plateaued prospectively (4.24-5.99), with highest rates for iCCA. ASMR showed a similar trend. Common risk factors included alcohol intake. smoking, overweight/obesity, and diabetes. Median overall survival was 10.25 months, shortest in pCCA and longest in dCCA. ctDNA analysis revealed actionable alterations, including FGFR2 fusions (5%), IDH1 (7%), BRAF (6%), and ERBB2(7%).
Conclusions
CCA incidence is rising. Accurate case identification, standardized diagnostics with biopsy confirmation, and close monitoring improve recognition. lntrahepatic CCA is the most frequent subtype, followed by distal and perihilar CCA.