Background: Adjuvant chemotherapy remains the standard of care following resection of pancreatic ductal adenocarcinoma (PDAC). However, despite advances with modern multi-agent regimens, most patients relapse, underscoring the need for alternative strategies. Neoadjuvant therapy offers several theoretical advantages, but evidence directly comparing it with upfront surgery remains limited. Objectives: To compare efficacy and postoperative safety outcomes between neoadjuvant therapy and upfront surgery among patients with resectable or borderline resectable PDAC. Design: We conducted a systematic review and meta-analysis of randomized clinical trials (RCTs) evaluating outcomes in patients with resectable or borderline resectable PDAC treated with either neoadjuvant chemotherapy and/or chemoradiotherapy or upfront surgery followed by adjuvant chemotherapy. Data sources and methods: Outcomes of interest included overall survival, disease-free survival (DFS), R0 resection rate, and postoperative complication rates. Literature searches were performed in PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials, supplemented by clinical trial registries, conference abstracts, and gray literature. Study selection and data extraction were conducted independently by two authors. Sensitivity and subgroup analyses were performed to assess sources of heterogeneity. Results: We included 13 RCTs, with one study excluded from the primary analysis due to high risk of bias. Neoadjuvant treatment did not confer a statistically significant benefit in overall survival (hazard ratio (HR) = 0.79; 95% confidence interval (95% CI), 0.58–1.10). However, neoadjuvant treatment was associated with improved DFS (HR = 0.79; 95% CI, 0.66–0.93) and a higher R0 resection rate (OR = 1.51; 95% CI, 1.04–2.19). There was no significant difference in the rate of major postoperative morbidity after resection (OR = 1.27; 95% CI, 0.61 – 2.62). Subgroup analyses revealed larger treatment effects in overall survival, DFS, and R0 resection rate in favor of neoadjuvant treatment among patients with borderline resectable PDAC. Conclusion: The survival advantage of neoadjuvant treatment in resectable or borderline resectable PDAC remains uncertain. Nonetheless, preoperative therapy improves DFS and R0 resection rates, with patients with borderline resectable disease deriving the greatest benefit. These findings should be interpreted with caution, given the limitations of the available evidence.
Jesus et al. (Fri,) studied this question.