Efficacy and safety of neoadjuvant therapy in resectable pancreatic cancer: Updated systematic review and meta-analysis of RCTs.

Abstract

e16458 Background: The clinical value of neoadjuvant therapy (NAT) for resectable pancreatic ductal adenocarcinoma remains debated. While NAT may improve pathologic endpoints such as margin-negative resection, its impact on perioperative safety and survival outcomes is uncertain, and newer randomized evidence has emerged. We performed an updated systematic review and meta-analysis of randomized controlled trials comparing NAT with upfront surgery to reassess efficacy and safety using contemporary data. Methods: We identified randomized controlled trials enrolling adults with resectable pancreatic cancer treated with NAT versus upfront surgery. Outcomes included major postoperative complications, nodal status at resection (N0), R0 resection margin, overall survival (OS), and progression-free survival (PFS). Risk ratios (RRs) were pooled for binary outcomes and hazard ratios (HRs) for time-to-event outcomes using random-effects models. Heterogeneity used I²; bias assessed via funnel plots. Results: Five trials contributed to major complications; NAT did not significantly increase major postoperative complications versus upfront surgery (RR 0.94, 95% CI 0.61–1.47; I² = 48.7%). Three studies reported nodal status; NAT showed a non-significant increase in N0 resection (RR 1.30, 95% CI 0.85–1.99; I² = 32.7%). Six studies reported margin status; NAT significantly improved R0 resection rates (RR 1.30, 95% CI 1.10–1.55; I² = 55.0%). For survival, NAT did not significantly improve OS (HR 0.87, 95% CI 0.67–1.11; I² = 43.9%) or PFS (HR 0.94, 95% CI 0.52–1.70; I² = 81.9%). Funnel plots did not suggest major publication bias, and leave-one-out analyses supported stability of pooled estimates. Conclusions: NAT improves R0 resection rates without increasing major complications, but survival benefits remain uncertain, particularly given heterogeneity and limited PFS data.