Surveillance Outcome and Genetic Findings in Individuals at High-Risk for Pancreatic Cancer.

INTRODUCTION: Pancreatic ductal adenocarcinoma (PDAC) has a poor 5-year survival rate. PDAC surveillance is recommended in high-risk individuals (HRI) with strong PDAC family history or a pathogenic germline variant (PGV) in a PDAC-susceptibility gene. We aimed to explore a potential correlation between genetic status, extent of family history, pancreatic findings, and surveillance implications in heterogeneous PDAC HRIs.

METHODS: 239 HRIs from 202 families were tested genetically and underwent prospective pancreatic surveillance for 6 years.

RESULTS: The cohort was divided into 3 groups: familial pancreatic cancer (FPC; 70 individuals, 54 families), familial non-FPC (81 individuals, 73 families), and hereditary pancreatic cancer (PC) (88 individuals, 75 families). PGVs were detected in 37.6% of all families including 11.1% of FPC families and 9.6% of familial non-FPC families. Hereditary PC group had earlier onset of PDAC compared with the other 2 groups. BRCA2 PGV carriers showed earlier onset of PDAC and pancreatic cysts. Of the 239 HRIs, PDAC was detected in 11 individuals (4.6%), with 73% diagnosed at an early stage; 4 (1.67%) had pancreatic neuroendocrine tumor; 6 (2.5%) had main-duct intraductal papillary neoplasm (IPMN); and 41 (17.15%) had side-branch IPMN. 17 individuals were referred to surgery and twelve were alive at end of study.

CONCLUSIONS: The percentage of PDAC was similar in the 3 groups studied. The hereditary PC group, and particularly BRCA2 PGV carriers, had an earlier age of PDAC onset. PGVs were detected in a significant percentage of PC HRIs. Surveillance appears effective for detection of early-stage PDAC and precursor lesions.