Impact of R0/R1 Margin Status on Overall Survival in Node-Positive Resected Pancreatic Ductal Adenocarcinoma: Meta-Analysis.

BACKGROUND

Microscopic residual disease (R1)and node-positive disease in resected pancreatic ductal adenocarcinoma (PDAC) are associated with worse survival. Some have suggested that obtaining an R0 resection is no longer relevant when patients have node-positive disease. A meta-analysis confirming this hypothesis is lacking.

PATIENTS AND

METHODS

A systematic review including studies with at least 50 patients with resected node-positive PDAC was conducted in PubMed, Embase, and Web of Science (inception to March 2025). Patients with node-negative disease were excluded. Primary outcome was overall survival (OS), comparing R0N+ and R1N+ resections. Hazard ratios (HR) with 95% confidence intervals (CI) represented outcome measures. Subgroup analysis included: application of the Royal College of Pathology protocol (RCP: standardized margin inking, axial slicing, and "1-mm rule") and receipt of neoadjuvant/adjuvant therapy.

RESULTS

Overall, 19,206 patients with resected node-positive PDAC from 16 retrospective studies were included. Most patients underwent upfront resection (96.3%), primarily pancreatoduodenectomy (84.2%). The overall R0N+ rate was 61.1%, differing significantly by application of RCP (yes [R1 = tumor within 1 mm of margin]: nine studies, 52.1%; unclear: four studies, 80.5%; no [R1 = tumor at margin ink only]: three studies, 61.5%; p = 0.0019). Overall, R1 negatively impacted OS (HR: 1.38; 95% CI: 1.21-1.59). RCP-only subgroup analysis confirmed worse OS in R1N+ resections (HR 1.25; 95% CI 1.10-1.42). Subgroup analysis by neoadjuvant/adjuvant therapy was not feasible.

CONCLUSIONS

Among patients with node-positive PDAC treated with upfront surgery, R1 resection remains associated with worse survival. In these patients, R0 resection should not be dismissed as a viable treatment goal until stronger RCP-compliant evidence emerges.