Multinational prospective study of liquid biopsy for early detection of pancreatic ductal adenocarcinoma

There is no clinically relevant blood-based assay for the detection of early-stage pancreatic ductal adenocarcinoma (PDAC). A prospective study of 1785 individuals with and without PDAC from four countries evaluated a blood-based microRNA (miRNA) assay including 10 miRNAs, and the composite PANXEON score that integrates the miRNA signature with carbohydrate antigen 19-9, for the detection of early-stage PDAC. The miRNA signature achieved an AUROC of 88.6% in the testing cohort, with a sensitivy of 83.8% for early-stage PDAC, while showing minimal cross-reactivity with other gastrointestinal cancers. In a cohort of 19 individuals, the miRNA signature levels decrease during neoadjuvant chemotherapy and after surgery, and increased before disease recurrence. When combined with CA 19-9 levels, the assay demonstrated a sensitivity of 86.8% for stage I-II PDAC, false-positive rates of 3.2% in low-risk controls and 15.6% in high-risk controls in the testing cohort. PANXEON demonstrated potential for detecting high-grade dysplasia in individuals with high-risk pancreatic cysts. The authors conclude that the study results present a composite biomarker that may complement existing strategies for the detection of early-stage PDAC.