Postsurgical circulating tumor DNA as a prognostic biomarker for relapse of resected pancreatic ductal adenocarcinoma.

BACKGROUND

Circulating tumor DNA (ctDNA) has been used to diagnose and monitor response to therapy in the setting of advanced pancreatic ductal adenocarcinoma (PDAC), but its utility in the adjuvant setting to monitor for relapse after curative resection is less understood.

METHODS

In this single-institution, retrospective study, we evaluated the use of ctDNA during the postoperative window (within 90 days from surgical resection and 30 days from the start of adjuvant therapy) and subsequent adjuvant/surveillance window (after the postoperative window) as prognostic biomarkers for relapse. We compared demographic and clinical characteristics among patients with radiographic disease relapse based on ctDNA positivity.

RESULTS

We identified 51 patients with PDAC who underwent curative-intent surgical resection between 2013 and 2024 and completed postoperative ctDNA testing. Median follow-up was 635 days, and 28 patients (54.9%) experienced disease relapse. ctDNA during the postoperative window had a sensitivity of 35.7% and specificity of 88.9% for prognosticating disease relapse after resection, with a positive predictive value (PPV) of 79.6% and negative predictive value (NPV) of 53.2%. ctDNA during the adjuvant/surveillance window had a sensitivity of 62.5%, specificity of 95.5%, PPV of 94.4%, and NPV of 67.7%. Patients with disease relapse as liver metastases had the highest rate of ctNA positivity (n = 10 of 12; 83.3%), followed by resection bed recurrence (n = 4 of 7; 57.1%) and nonliver distant metastatic recurrence (n = 4 of 9; 44.4%).

CONCLUSION

Positive ctDNA is a strong prognostic factor for relapse after resection for PDAC; however, ctDNA testing lacks sensitivity to replace conventional surveillance testing in patients with resected PDAC.