PURPOSE Biomarkers that facilitate detection of pancreatic cancer during a potentially curable stage are a significant public health need. We designed a 5-plex serum biomarker signature to detect stage I and II pancreatic ductal adenocarcinoma (PDAC) in high-risk surveillance populations. In two previous validations performed in two independent cohorts, the assay signature distinguished stage I and II PDAC from high-risk individuals in surveillance with high sensitivity and specificity. In this study, we evaluated assay performance in stage III and IV PDAC and non–high-risk individuals. METHODS Signature analytes were retrospectively measured in 619 serum samples from a blinded independent cohort of stage III and IV PDAC cases (n = 224) and non–high-risk controls (n = 395). A positive or negative result for PDAC was generated from a predefined cutoff established during assay development. The assay's performance in this study was compared with its performance in the previous validations. RESULTS The signature panel distinguished stage III and IV PDAC from controls with 87.9% sensitivity (95% CI, 82.9 to 91.9) and 97.7% specificity (95% CI, 95.7 to 99.0). The assay demonstrated significantly higher sensitivity in stage III and IV PDAC than stage I and II cases (77.3% 95% CI, 72.3 to 81.8; P = .002) and significantly higher specificity in non–high-risk controls (97.7%) compared with high-risk controls (92.2% 95% CI, 90.4 to 93.7; P < .001). CONCLUSION These results demonstrate high assay performance in patients with stage III and IV PDAC and non–high-risk individuals. Although the test is intended for detection of stage I and II PDAC in high-risk surveillance populations, it can be used to detect all stages of PDAC, including advanced disease.
Borazanci et al. (Wed,) studied this question.