Postoperative ctDNA strongly predicts recurrence and survival in resected pancreatic cancer
Investigators conducted a systematic review and meta-analysis of 44 studies encompassing more than 2,500 patients to evaluate the prognostic value of circulating tumor DNA, circulating tumor cells, and extracellular vesicles in resected pancreatic ductal adenocarcinoma. Preoperative ctDNA positivity was associated with worse overall survival and recurrence-free survival, while postoperative ctDNA detection showed a markedly stronger association with both endpoints. Circulating tumor cells also correlated with inferior recurrence-free survival, and extracellular vesicle markers consistently indicated adverse outcomes despite high heterogeneity. These findings consolidate evidence that ctDNA monitoring can serve as a robust molecular tool for risk stratification and surveillance in pancreatic cancer, offering a potential complement to conventional imaging and CA19-9 testing.
The original study
Liquid Biopsy in Resected Pancreatic Ductal Adenocarcinoma: A Systematic Review and Meta-Analysis.
- Authors
- Qian J, Ceuppens S, Tirukkovalur NV, He HZ, Zheng SY, Suppok R, et al.
- Journal
- Annals of surgical oncology
- Type
- Journal Article
- PMID
- 42665699
Original abstract
BACKGROUND: Distinct liquid biopsy modalities are emerging as promising tumor-specific biomarkers to monitor treatment response and predict survival in pancreatic ductal adenocarcinoma (PDAC). Circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), and extracellular vesicles (EVs) may reflect underlying systemic disease burden and complement conventional imaging or CA19-9 assessment. This systematic review and meta-analysis evaluated the prognostic significance of liquid biopsy biomarkers in patients with resected PDAC. METHODS: A systematic review and meta-analysis was performed in accordance with PRISMA guidelines. Studies published until 1 July 2025 evaluating ctDNA, CTCs, or EVs in patients with resected PDAC, with or without neoadjuvant therapy, were evaluated. Primary outcomes were overall survival (OS) and recurrence-free survival (RFS). Study quality was assessed using the QUADAS-2 tool. RESULTS: The meta-analysis included 44 studies (26 ctDNA, 12 CTC, and 6 EV studies; >2,500 patients). Preoperative ctDNA positivity was associated with worse OS (pooled hazard ratio [HR], 2.53; 95% confidence interval [CI], 1.86-3.44) and RFS (HR, 2.28; 95% CI, 1.67-3.11), with low-to-moderate heterogeneity. Postoperative ctDNA positivity demonstrated stronger associations with worse OS (HR, 5.15; 95% CI, 1.57-16.88) and RFS (HR, 3.12; 95% CI, 2.01-4.82), with moderate-to-substantial heterogeneity. Preoperative CTC positivity was associated with inferior RFS (HR, 2.70; 95% CI, 1.32-5.52), with substantial heterogeneity. In individual studies, EV-based biomarkers demonstrated consistent adverse outcomes. However, quantitative pooling was not feasible due to marked heterogeneity. CONCLUSION: In resected PDAC, preoperative ctDNA is a robust predictor of recurrence and survival. Both CTCs and EVs show biologically compelling but assay-dependent prognostic signals.