Does Adjuvant Therapy in Invasive Intraductal Papillary Mucinous Neoplasm of the Pancreas Improve Survival? A Systematic Review and Meta‐Analysis Using Trial Sequential Analysis

Objective: This meta-analysis aims to evaluate the efficacy of adjuvant therapy (ADJ) in patients with resected invasive IPMNs, compared with follow-up (FUP). Methods: A random effects meta-analysis was performed. Meta-regression analysis was used to clarify heterogeneity. The trial sequential analysis was used to test Type I and Type II errors, defining the required information size (RIS). The primary endpoint was OS, and the secondary endpoint was DFS. Results: The accrued sample size (AIS) was 2422 patients for OS and 493 patients for DFS. OS and DFS in the ADJ arm were similar to the FUP arm (HR 1.21; 95% CI 0.81−1.79, p = 0.349 and HR 0.98; 95% CI 0.64−1.51, p = 0.936). The RIS were 2422 for OS and 254 for DFS, allowing the exclusion of Type II errors. For the primary endpoint, heterogeneity was high (I2 = 98%). Meta-regression analysis showed that, although considering two groups equal for confounding covariates, OS in the ADJ and FUP arms remains similar. A subgroup analysis showed that node-positive patients have improved OS after adjuvant therapy administration (HR 1.86; 95% CI 1.39; 2.47, p < 0.001). Conclusion: Adjuvant therapy should not be administered indiscriminately to all patients. Node-positive invasive IPMN seems to have an improved OS. Trial Registration: PROSPERO 2024 CRD42024561326.