Validation of a Serum-Based Biomarker Signature for Detection of Early-Stage Pancreatic Ductal Adenocarcinoma

BACKGROUND & AIMS: This study's goal was to clinically validate the performance of PancreaSure (Immunovia, Inc), a serum biomarker signature composed of tissue inhibitor of metalloproteinase 1, intercellular adhesion molecule 1, cathepsin D, thrombospondin 1, and carbohydrate antigen 19-9 for detection of early-stage pancreatic ductal adenocarcinoma (PDAC) in an independent cohort. METHODS: Signature analytes were retrospectively measured in serum samples from a blinded cohort of stage I and stage II PDAC cases and genetic and/or familial high-risk controls. A predictive signal for PDAC was generated from a predefined cutoff established in a previous model development study optimized at 98% specificity. Diagnostic sensitivity and specificity were evaluated on the full cohort. McNemar or 2-proportion z tests were used to compare test performance between stage I and stage II cases, and between controls with and without a germline mutation and/or familial susceptibility to PDAC. Diagnostic certainty of test results was evaluated using a Monte Carlo simulation. RESULTS: PancreaSure distinguished early-stage PDAC (n = 202) from high-risk controls (n = 864) with 78.5% sensitivity (95% CI, 72.5%-83.9%) and 93.5% specificity (95% CI, 91.9%-95.2%), significantly outperforming carbohydrate antigen 19-9 alone (P < .001). The test performed consistently between stage I and II PDAC and between controls with and without genetic or familial susceptibility. In addition, 93.7% of all samples were classified as PDAC-positive or PDAC-negative with 100% certainty. Only 1.8% of all samples were classified with <80% certainty. CONCLUSIONS: These findings indicate that PancreaSure is a high-performing biomarker test to aid in the detection of early-stage PDAC. Overall, this work represents an important step toward improving early-stage diagnostic success.