Abstract
Background: Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer with poor prognosis due to late-stage diagnosis, limited surgical resectability, and frequent recurrence. Traditional biomarkers like CA19-9 and imaging techniques often fail to detect minimal residual disease (MRD) or early recurrence. Circulating tumor DNA (ctDNA) is a promising non-invasive biomarker that may provide early detection of disease recurrence, offering a potential improvement in patient management. This study aimed to assess the utility of ctDNA as a prognostic tool for PDAC patients, specifically in predicting recurrence and overall survival (OS). Methods: This retrospective study analyzed data from 39 PDAC patients who underwent surgery and were monitored for ctDNA levels using Signatera™, a tumor-informed multiplex PCR next-generation sequencing assay. Blood samples were collected both preoperatively and postoperatively, and ctDNA levels were measured to detect MRD. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of ctDNA were compared with CA19-9 in detecting disease recurrence. Clinical outcomes, including progression-free survival (PFS) and OS, were evaluated in relation to ctDNA status. Results: Among 39 patients, 153 plasma samples were analyzed, with 17 patients testing positive for ctDNA. Sensitivity of ctDNA in detecting relapse was 91%, compared to 83% for CA19-9, with combined testing reaching 98% sensitivity. ctDNA positivity was associated with significantly shorter OS and PFS, with patients testing negative for ctDNA having a median OS of 37.6 months versus 13.4 months in ctDNA-positive patients (p = 0.003). The median time from ctDNA positivity to imaging-confirmed relapse was 81 days. Positive ctDNA was also linked to higher rates of lymphovascular invasion and positive surgical margins, highlighting the aggressive nature of the disease in these patients. Conclusions: CtDNA is a highly sensitive and specific biomarker for detecting MRD and predicting recurrence in PDAC patients, offering superior performance over CA19-9. Positive ctDNA results were associated with worse prognosis, including shorter OS and PFS, and may help guide treatment decisions. These findings suggest that ctDNA could be a valuable tool for personalized management in PDAC, though further prospective studies are needed to validate its clinical role in treatment stratification.