ctDNA in Pancreatic Adenocarcinoma: A Critical Appraisal

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest malignancies due to late diagnosis and limited treatment options. Circulating tumor DNA (ctDNA) is a promising, minimally invasive biomarker that could improve the clinical outcomes of patients with PDAC by enabling early disease detection, minimal residual disease (MRD) assessment, precise prognostication, and accurate treatment monitoring. CtDNA has prognostic as well as predictive value in both resectable and metastatic settings, with serial measurements enhancing risk stratification and recurrence prediction beyond CA19-9. However, despite the promise, the true potential of ctDNA has not yet been fulfilled in patients with PDAC. The current limitations include a low sensitivity of ctDNA assays in early stage PDAC, challenges in the assay interpretation due to the specific nature of ctDNA shedding in PDAC, inter-patient heterogeneity, and technical variability. As precision oncology advances, ctDNA will be a powerful tool for personalized care in PDAC, but rigorous validation of its use within specific clinical contexts is still needed before the true potential of ctDNA is realized for patients with PDAC.