Pancreatic Cancer Early Detection Biomarkers for High-Risk Individuals: Insights From the PRECEDE Consortium

Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest cancers due to its asymptomatic progression, late-stage diagnosis, and treatment resistance. Efforts in early detection have centered on identifying imaging features and liquid biopsy biomarkers capable of detecting PDAC and its high-grade precursors before clinical symptoms arise in patients at elevated risk of PDAC development. Classical imaging-based surveillance strategies, aligned with current guidelines, form the foundation of screening high-risk individuals, while organ-specific fluid analyses-such as cyst fluid and pancreatic juice-offer promising complementary tools with enhanced specificity. Recent advances in radiomics, liquid biopsy, microbiome, and multi-omics profiling are expanding the frontier of early detection. Despite advances, significant challenges persist. Precursor lesions are difficult to non-invasively diagnose; are not radiologically or endosonographically visible, or cannot be definitively graded prior to resection. Though biomarkers show promise for early detection, they present unique challenges: early-stage neoplasias release low levels of many biomarkers and thresholds for these biomarkers that define malignant transformation-and thus guide surgical intervention-remain poorly established. Multi-institutional initiatives like the Pancreatic Cancer Early Detection consortium (PRECEDE) are critical to bridging discovery and clinical translation. Our international cohort study of high-risk individuals was designed to discover and validate diagnostic biomarkers according to the PROBE study design. Continued collaboration, technological integration, and patient-centered approaches are essential to transform early detection research into tangible survival benefits for those at risk of PDAC.