[Comparison of clinical outcomes between neoadjuvant therapy and upfront surgery in resectable pancreatic cancer: a...

Objective: To systematically compare the clinical outcomes of neoadjuvant therapy (NAT) versus upfront surgery (US) in patients with resectable pancreatic cancer. Methods: This meta-analysis was conducted following established guidelines. Reaearch articles were searched in PubMed, Embase, Cochrane Library, Web of Science, CNKI, and VIP databases from their inception to May 19,2025, using search terms including "pancreatic neoplasms" "pancreas tumor" "neoadjuvant therapy" "randomized controlled trial" and their Chinese equivalents. High-quality randomized controlled trial (RCT) comparing NAT with US in resectable pancreatic cancer patients were included. Two researchers independently performed literature screening,data extraction,and quality assessment. Overall survival (OS) was evaluated using hazard ratios (HR) with 95%CI,while R0 resection rate,pN0 rate,postoperative complication rate,and 90-day postoperative mortality were assessed using risk ratios (RR) with 95%CI. Heterogeneity was assessed using the Q-test and I² statistic. Publication bias was evaluated using funnel plots and Egger's test,with the trim-and-fill method used to assess its impact on the results. Sensitivity analysis was conducted using the leave-one-out method to determine the robustness of the pooled effect estimates. Results: Seven RCTs involving 1 026 patients were included (NAT group: n=553;US group: n=473). The initial meta-analysis of five studies on OS showed no statistically significant difference between the NAT and US groups (HR=0.85,95%CI: 0.62 to 1.17,P=0.320). However,sensitivity analysis performed by sequentially removing individual studies identified and excluded a source of heterogeneity. After this exclusion,the analysis revealed that NAT was associated with significantly longer OS time compared to US (HR=0.75,95%CI: 0.62 to 0.90,P=0.003). Furthermore,NAT significantly improved the R0 resection rate (RR=1.28,95%CI: 1.07 to 1.55,P=0.008) and the pN0 rate (RR=2.12,95%CI: 1.59 to 2.82,P<0.01). No significant differences were found between the two groups in terms of postoperative complication rate (RR=0.95,95%CI: 0.81 to 1.13,P=0.590) or 90-day postoperative mortality (RR=0.67,95%CI: 0.24 to 1.87,P=0.450). Conclusions: Based on the current best available evidence from RCT,for resectable pancreatic cancer, neoadjuvant therapy improves the R0 resection rate and pN0 rate without increasing postoperative complications or mortality compared to the traditional approach of upfront surgery. However,these findings warrant further validation by more high-quality RCT.