Utility of pancreatic cancer screening and detection in patients with pathogenic germline variants.

Abstract

690 Background: Most patients with pancreatic cancer (PC) present with late-stage (unresectable or metastatic) disease. Certain high-penetrance germline variants increase PC risk, for which there are imaging-based guidelines for screening to potentially diagnose patients earlier. This study aims to describe the screening compliance of patients with germline Pathogenic/Likely Pathogenic variants (PVs) at high-risk for developing PC. Methods: Patients who underwent genetic testing between 2021-2024 were identified from prospectively maintained Breast and Gastroenterology clinic databases. Genes with PVs for PC included ATM, BRCA2, CDKN2A, STK11, 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 reason unrelated to screening (incidental) based on the indication for ordering the study. The detection of PC and subsequent outcomes were longitudinally tracked. Results: Of 1,525 patients that underwent genetic testing, 192 had PVs for PC. Of those with PVs, 130 (68%) had subsequent imaging and 43 (33%) were screened intentionally to look for PC. The most common PVs included BRCA2 (63, 48%) ATM (13, 10%), BRCA 1 (68, 52%), CDKN2A (6, 4.6%), and PALB2 (8, 6.1%). The most commonly used modality was CT in 88 patients (68%), followed by MRI (41, 32%), and no patients underwent EUS. Three patients developed PC after genetic testing, however, none had PVs. Discussion: Our findings highlight a critical gap in guideline-recommended screening for patients with a genetic predisposition to PC. Despite 192 patients with PVs meriting PC screening, only a third were intentionally screened. Although MRI and EUS have a higher sensitivity for detection, CT scans were the most used modality. Conclusions: This large single center study supports the need for a more systematic, coordinated approach to pancreatic cancer screening in genetically high-risk patients. Future work will investigate costs related to pancreatic cancer screening as well as strategies for more effectively identifying patients at risk that may benefit from a screening program.