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

Early detection of pancreatic ductal adenocarcinoma (PDAC) could extend patient survival, and biomarkers to facilitate this are urgently needed. Here, we performed a second independent validation of PancreaSure, a 5-plex serum biomarker signature to detect early-stage PDAC in high-risk individuals. In contrast to the first validation, this study's cohort was preemptively balanced for age and sex and only included samples stored for fewer than 5 years. The primary endpoint was to measure test sensitivity against the performance target of 65%. Measuring specificity against the performance target of 90% and comparing test performance to that of carbohydrate antigen 19-9 (CA 19-9) alone were secondary endpoints. Signature analytes were retrospectively measured in serum from a blinded independent cohort of Stage I and II PDAC cases and high-risk controls. A predictive signal for PDAC was generated from a predefined cutoff established in a previous model development study. PancreaSure distinguished early-stage PDAC from controls with 76.5% sensitivity (95% CI, 67.7-83.9), significantly higher than the performance target (p = 0.005). PancreaSure achieved 87.8% specificity (95% CI, 83.9-91.4), similar to the performance goal, and significantly outperformed sensitivity of CA 19-9 alone (p = 0.02). These results confirm that PancreaSure performs well at detecting early-stage PDAC in high-risk individuals.