Neoadjuvant therapy versus upfront surgery in resectable pancreatic cancer: reconstructed patient-level meta-analysis of randomized clinical trials

• Published in: BJS open 2024-09, Vol.8 (5)
• Main Authors: Aliseda, Daniel, Martí-Cruchaga, Pablo, Zozaya, Gabriel, Blanco, Nuria, Ponz, Mariano, Chopitea, Ana, Rodríguez, Javier, Castañón, Eduardo, Pardo, Fernando, Rotellar, Fernando
• Format: Article
• Language: English
• Subjects: Bayes Theorem; Carcinoma, Pancreatic Ductal - mortality; Carcinoma, Pancreatic Ductal - pathology; Carcinoma, Pancreatic Ductal - surgery; Carcinoma, Pancreatic Ductal - therapy; Humans; Neoadjuvant Therapy; Pancreatectomy; Pancreatic Neoplasms - drug therapy; Pancreatic Neoplasms - mortality; Pancreatic Neoplasms - pathology; Pancreatic Neoplasms - surgery; Pancreatic Neoplasms - therapy; Randomized Controlled Trials as Topic
• ISSN: 2474-9842; 2474-9842
• DOI: 10.1093/bjsopen/zrae087

Abstract Background Neoadjuvant treatment has shown promising results in patients with borderline resectable pancreatic ductal adenocarcinoma. The potential benefits of neoadjuvant treatment on long-term overall survival in patients with resectable pancreatic ductal adenocarcinoma have not yet been established. The aim of this study was to compare long-term overall survival of patients with resectable pancreatic ductal adenocarcinoma based on whether they received neoadjuvant treatment or underwent upfront surgery. Methods A systematic review including randomized clinical trials on the overall survival outcomes between neoadjuvant treatment and upfront surgery in patients with resectable pancreatic ductal adenocarcinoma was conducted up to 1 August 2023 from PubMed, MEDLINE and Web of Science databases. Patient-level survival data was extracted and reconstructed from available Kaplan–Meier curves. A frequentist one-stage meta-analysis was employed, using Cox-based models and a non-parametric method (restricted mean survival time), to assess the difference in overall survival between groups. A Bayesian meta-analysis was also conducted. Results Five randomized clinical trials comprising 625 patients were included. Among patients with resectable pancreatic ductal adenocarcinoma, neoadjuvant treatment was not significantly associated with a reduction in the hazard of death compared with upfront surgery (shared frailty HR 0.88, 95% c.i. 0.72 to 1.08, P = 0.223); this result was consistent in the non-parametric restricted mean survival time model (+2.41 months, 95% c.i. −1.22 to 6.04, P < 0.194), in the sensitivity analysis that excluded randomized clinical trials with a high risk of bias (shared frailty HR 0.91 (95% c.i. 0.72 to 1.15; P = 0.424)) and in the Bayesian analysis with a posterior shared frailty HR of 0.86 (95% c.i. 0.70 to 1.05). Conclusion Neoadjuvant treatment does not demonstrate a survival advantage over upfront surgery for patients with resectable pancreatic ductal adenocarcinoma. This study aimed to assess the impact of neoadjuvant treatment compared with upfront surgery on the long-term overall survival of patients with resectable pancreatic ductal adenocarcinoma. A systematic review and reconstructed patient-level survival data meta-analysis including five RCTs with 625 patients revealed that neoadjuvant treatment did not significantly reduce the hazard of death compared with upfront surgery in resectable pancreatic ductal adenocarcinoma pat