Abstract Background: Pancreatic cancer (PC) remains one of the deadliest malignancies, due to late-stage presentation and limited risk-reduction strategies. Certain high-penetrance germline variants increase pancreatic cancer risk, and the NCCN recommends screening for this unique population. As genetic testing becomes more common, mutations predisposing to pancreatic cancer can be detected. This study aims to describe the screening compliance of patients at a single center with germline Pathogenic/Likely Pathogenic variants (PVs) at high-risk for developing pancreas cancer. Methods: Patients who underwent genetic testing between 2010-2024 were identified from a prospectively maintained Breast and Gastroenterology clinic database. Patients without confirmed genetic testing documentation were excluded. We included patients with moderate and high-penetrance PVs for pancreatic cancer (ATM, BRCA2, CDKN2A and STK11), as well as a family history of PC with BRCA1 or PALB2. After the date of genetic testing, abdominal imaging was reviewed including the modality (magnetic resonance imaging MRI, computed tomography CT, endoscopic ultrasound EUS), and whether imaging was for screening (intentional) or another issue unrelated to screening (incidental) based on the indication for ordering the study. The detection of pancreatic cancer and outcomes were additionally tracked. Results: The most common mutation found through genetic testing was BRCA2 which was found in 13 (1. 88%) of patients, however other mutations found included ATM (n=9, 1. 3%), BRCA 1 (n=9, 1. 3%), CDKN2A (n=4, 0. 58%), and PALB2 (n=2, 0. 29%). For all patients who received genetic testing, 285 (41. 36%) had incident imaging done while (39) 5. 66% were intentional for PC screening and 365 had no imaging. Patients received follow-up imaging in 49. 06% of patients. The most used modality was CT in 163 patients (87. 17%), followed by MRI in 22 (11. 76%), and 2 patients who underwent EUS (1. 07%). Of the 53 patients with mutations associated with pancreatic cancer, 39 had abdominal imaging; 7 were intentional and 32 incidentals. 26/39 had follow-up abdominal imaging while 13 patients did not. All 39 patients are PC free; however, from the entire cohort studied, there was 1 diagnosis of pancreatic cancer in a patient with no PV. Discussion: Our findings highlight a critical gap in guideline-recommended screening for patients with a genetic predisposition to pancreatic cancer. Despite 53 patients having confirmed mutations, only 26 underwent imaging and only 7 were intentionally screened for pancreas cancer. Although MRI and EUS have a higher sensitivity for detection, CT scans were the most used imaging modality. Conclusions: This study supports the need for a more systematic, coordinated approach to pancreatic cancer screening in genetically high-risk patients. Our institution has launched a high-risk pancreas screening program to address this gap and will follow the outcomes of this effort in future work. Citation Format: Pranati D. Shah, Alexander Gavralidis, Liang Ji, Jordan Klaassen, Enxi Chen, Derek Tai, Kevin Bera, Joseph Hemry, Harrison Jennings, Sumaia G. Khoury, Mina Batros, Skey Balang, Timothy Yen, Gayathri Nagaraj, Raja R. Narayan. Impact of germline pathogenic variants on pancreatic cancer screening and outcomes abstract. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research—Emerging Science Driving Transformative Solutions; Boston, MA; 2025 Sep 28-Oct 1; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2025;85 (18Suppl₃): Abstract nr B064.
Shah et al. (Sun,) studied this question.