Site-specific limitations of ctDNA in PDAC surveillance: imaging detects pulmonary and local recurrence missed by liquid biopsy.

[OBJECTIVES] To evaluate the concordance between circulating tumor DNA (ctDNA) and imaging in the postoperative surveillance of patients with resected pancreatic ductal adenocarcinoma (PDAC).

[METHODS] This single-center, retrospective study included 50 patients with resected PDAC who underwent both ctDNA testing and surveillance imaging between January 2015 and February 2025. Imaging included CT or CT/MRI of the chest, abdomen, and pelvis at 3-6 month intervals, with ctDNA testing performed on a similar schedule. Two abdominal radiologists independently reviewed all imaging for recurrence, defined by new or enlarging lesions; discrepancies were resolved by consensus. ctDNA recurrence was defined as the detection of tumor-specific mutations. Concordance was assessed at the patient level.

[RESULTS] Among 50 patients (median age 69.5 years, 33 men, 17 women), ctDNA and imaging were concordant in 39 (78%): 22 had recurrence and 17 did not. Discordance occurred in 11 patients, 10 of whom had radiologic recurrence with negative ctDNA. Most discordant lesions were located in the lung (n = 5, median size 0.4 cm) or surgical bed (n = 5, median size 2.0 cm). Radiologic recurrences preceded negative ctDNA test results in all 10 of these cases. One patient had positive ctDNA without imaging recurrence over 497 days of follow-up. At the organ level, 1/6 (17%) of lung metastases and 10/15 (67%) of local recurrences by imaging were detected by ctDNA. All lymph node, liver, peritoneal, and bone metastases were detected by ctDNA.

[CONCLUSION] Positive ctDNA tests after PDAC resection correlates with radiologic recurrences in the lymph nodes, liver, peritoneum, and bones. However, radiologic recurrences in the lungs or surgical bed are commonly associated with a negative ctDNA test. Radiologists should scrutinize the latter two sites even when ctDNA tests are negative.