The PancreaSure Multianalyte Blood Test Performs Well at Distinguishing Early-Stage Pancreatic Ductal Adenocarcinoma from High-Risk Controls: A Retrospective Secondary Analysis

Background/Objectives: Biomarkers that can facilitate early detection of pancreatic cancer and extend patient survival are a significant unmet need. PancreaSure is a serum biomarker signature that performed well at distinguishing Stage I and II pancreatic ductal adenocarcinoma (PDAC) from both high-risk and non-high-risk controls in two previous validations. The goal of this study was to perform a secondary analysis of test performance exclusively in individuals at high risk of PDAC due to a pathogenic variant in a susceptibility gene or strong family history of the disease. To this end, we extracted and analyzed raw data from appropriate samples used in the prior validations. Methods: Data from the two prior validations were pooled at the participant level, and sensitivity and specificity were estimated as pooled proportions with exact binomial 95% confidence intervals. One-sided exact binomial tests were used to compare the performance of the PancreaSure test to the performance goals of 65% sensitivity and 90% specificity. Results: PancreaSure detected early-stage PDAC with 77.5% sensitivity (95% CI, 66.0-86.5) and 93.6% specificity (95% CI, 91.8-95.1), significantly outperforming predefined success criteria. Test performance was consistent between Stage I (80.0% sensitivity) and Stage II (75.6% sensitivity) PDAC cases. PancreaSure also demonstrated favorable performance in individuals with only genetic susceptibility to PDAC (84.8% sensitivity, 94.5% specificity), with only a family history of the disease (79.2% sensitivity, 93.7% specificity), and with high-penetrance variants. Conclusions: The performance demonstrated by PancreaSure in genetic/familial high-risk individuals further suggests that it has the potential to facilitate early detection of PDAC in surveillance populations and warrants prospective evaluation as an adjunct to imaging.