Simple SummaryPancreatic ductal adenocarcinoma (PDAC) is a highly lethal disease, and the currently available techniques for its detection are either invasive or less sensitive. To overcome this limitation, we present here a multiplexed point-of-care test that combines systemic inflammatory response biomarkers, standard laboratory tests, and nanoparticle-based blood tests. This test provides a “risk score” for each individual under investigation, allowing clinicians to distinguish between PDAC patients and healthy subjects accurately and to determine the optimal diagnostic and therapeutic care pathway for each patient. As a result, this work may help advance progress in the early detection of PDAC and contribute to the development of screening programs for high-risk populations.AbstractPancreatic ductal adenocarcinoma (PDAC) is a highly lethal disease, for which mortality closely parallels incidence. So far, the available techniques for PDAC detection are either too invasive or not sensitive enough. To overcome this limitation, here we present a multiplexed point-of-care test that provides a “risk score” for each subject under investigation, by combining systemic inflammatory response biomarkers, standard laboratory tests, and the most recent nanoparticle-enabled blood (NEB) tests. The former parameters are routinely evaluated in clinical practice, whereas NEB tests have been recently proven as promising tools to assist in PDAC diagnosis. Our results revealed that PDAC patients and healthy subjects can be distinguished accurately (i.e., 88.9% specificity, 93.6% sensitivity) by the presented multiplexed point-of-care test, in a quick, non-invasive, and highly cost-efficient way. Furthermore, the test allows for the definition of a “risk threshold”, which can help clinicians to trace the optimal diagnostic and therapeutic care pathway for each patient. For these reasons, we envision that this work may accelerate progress in the early detection of PDAC and contribute to the design of screening programs for high-risk populations.