Detecting circulating tumor DNA (ctDNA) in patients with localized pancreatic ductal adenocarcinoma (PDAC) can help predict outcomes and guide surgical decision-making.

• Mutant KRAS ctDNA was present in 19% of patients at diagnosis, with levels dropping to 4.6% after neoadjuvant chemotherapy (NAC).
• The presence of both KRAS and TP53 ctDNA at diagnosis was associated with a nearly six-fold increased risk of shorter overall survival (OS) (adjusted hazard ratio 5.66, p < 0.001).
• Higher ctDNA variant allele frequency during treatment also indicated a worse prognosis (adjusted hazard ratio 1.14, p = 0.028).

These findings suggest that ctDNA assessments can be integral in evaluating treatment response and risk stratification in localized PDAC.