Risk-stratified surveillance for individuals in the UK at high risk of developing pancreatic cancer: Outcomes from the European Registry of Hereditary Pancreatic Diseases (EUROPAC)

BACKGROUND: Surveillance of individuals with a familial predisposition to pancreatic ductal adenocarcinoma (PDAC) is likely to increase overall survival. Our objective was to determine the impact of EUROPAC risk-stratification (Family Risk, FR), in such predisposed individuals. METHODS: Observational study of registered asymptomatic individuals undergoing surveillance for PDAC. Individuals without a known pathogenic variant (PV-), ineligible for genetic assessment in the NHS, in whom significant pancreatic lesions were found, were subjected to additional germline testing. RESULTS: Between January 2000 and April 2025, 893 individuals started surveillance, median age of 52 years. 508 individuals (404 PV- and 104 with a pathogenic variant (PV+)) in the 20 years prior to 2020 without stratification were compared to 385 (269 PV- and 116 PV+) in the five years from 2020 who had FR risk-stratification applied. Four (0·8 %) individuals had actionable pancreatic findings prior to risk stratification vs. 14 (3·6 %), who underwent risk-stratified surveillance (p = 0·001). Pancreatic lesions deemed operable were found in three (0·6 %) and 11 (3 %), p = 0·007, with two (0·4 %) and nine (2 %) undergoing resection, p = 0·009, respectively. PV- individuals with significant findings were subsequently found to contain mutations, many not in the UK genetics test directory, provided the FR was > 30. The median (IQR) time in surveillance prior to a lesion being detected was four (2 - 7) years. Overall, 78 % of EUROPAC detected precursor lesions or pancreatic cancers were stage II or lower. CONCLUSION: The risk-stratified group (FR) identifies neoplastic pancreatic lesion in individuals, regardless of PV status suggesting the key usefulness of this approach.