In resected pancreatic ductal adenocarcinoma (PDAC), preoperative circulating tumor DNA (ctDNA) positivity is a strong predictor of poor overall and recurrence-free survival.

• Preoperative ctDNA positivity is linked to worse overall survival (hazard ratio [HR] 2.53) and recurrence-free survival (HR 2.28).
• Postoperative ctDNA positivity shows even stronger associations with worse survival outcomes (HR 5.15 overall, HR 3.12 recurrence-free).
• Circulating tumor cells (CTCs) also indicate inferior recurrence-free survival, but further assay standardization is needed.

Surgeons should consider ctDNA testing pre- and postoperatively to better inform prognosis and treatment strategies for PDAC patients.