Increasing Use of Germline Genetic Testing in Pancreatic Ductal Adenocarcinoma and Relationship to Clinical Outcome: A Single-Institution Study.

Abstract

Precision therapies have improved outcomes in pancreatic ductal adenocarcinoma (PDAC) and highlight the utility of germline genetic testing (GGT) in clinical decision making. Here, we investigate the association of GGT of individuals diagnosed with PDAC over time to identify changes in testing patterns and the relationship of testing with clinicopathologic parameters and overall survival (OS). The frequency of GGT of 979 patients with PDAC treated at the Roswell Park Comprehensive Cancer Center (RPCCC) between 2017 and 2024 was determined. Factors associated with performing testing and having a germline pathogenic variant (GPV) were assessed. OS and the impact of precision treatment were evaluated. Patients with PDAC being treated at RPCCC that had GGT increased from 16.5% in 2017 to 57.6% in 2024. Patients with testing had improved OS compared with patients who did not (HR, 0.46). Individuals of older age, without a personal history of other cancers, without a family history of pancreatic cancer, with advanced disease, and with poorly differentiated tumors were less likely to have testing performed. Individuals with a personal history of other cancers were more likely to have a GPV. Of the 425 patients diagnosed with PDAC that had testing, 58 (13.6%) had a GPV detected. Of patients with testing, 12 had actionable mutations in <i>BRCA1/2</i>, seven of whom were subsequently treated with olaparib. Three patients harbored actionable mutations in <i>MSH6</i>, with one patient subsequently treated with pembrolizumab. Patients who received therapy informed by testing results had improved OS (HR, 0.09). GGT prevalence has increased at RPCCC and informed treatment decisions. Universal point-of-care testing is being implemented with the goal of completing testing for all patients with PDAC seen at RPCCC.