Postoperative Tumor-Informed Circulating Tumor DNA Status for Molecular Residual Disease Detection After Curative-Intent Resection of Pancreatic Ductal Adenocarcinoma: A Systematic Review and Meta-Analysis.
Wajahat Mirza, Minhaj Rafi, Zubair Siddiqui et al.
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In 30 seconds
This systematic review and meta-analysis pooled observational evidence on postoperative tumor-informed circulating tumor DNA (ctDNA) as a marker of molecular residual disease after curative-intent resection of pancreatic ductal adenocarcinoma. Five cohorts contributed 237 patients to the radiological recurrence analysis. Compared with ctDNA-negative patients, ctDNA-positive patients had a higher risk of radiological recurrence (RR 2.50; 95% CI 1.90-3.28) and poorer disease-free and overall survival. The findings support prognostic value, but do not establish that ctDNA-guided management improves outcomes.
Key findings
- Postoperative ctDNA positivity was associated with increased radiological recurrence (RR 2.50; 95% CI 1.90-3.28; I²=20%).
- ctDNA positivity was associated with poorer disease-free survival (HR 8.11; 95% CI 3.51-18.73; I²=45%).
- ctDNA positivity was associated with poorer overall survival (HR 5.15; 95% CI 2.67-9.94; I²=0%).
- Recurrence risk was higher in both early-MRD/landmark and surveillance subgroups, with no statistically significant subgroup difference (P = 0.17).
Why it matters
Postoperative recurrence is common in pancreatic ductal adenocarcinoma, while conventional imaging and CA19-9 have limited sensitivity for molecular residual disease. These pooled associations suggest tumor-informed ctDNA may help identify patients at higher risk and inform future risk-stratification research. However, prognostic association alone does not show that changing surveillance or treatment based on ctDNA improves patient outcomes.
What to keep in mind
The evidence came from five observational cohorts and was described as limited and heterogeneous. A negative ctDNA result did not reliably exclude residual disease, and the review notes that prospective interventional studies are needed.