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

## TL;DR

This study finds that adjuvant therapy does not improve survival for most patients with invasive IPMN, but may benefit those with node-positive disease.

## Contribution

The study identifies a specific subgroup (node-positive patients) who may benefit from adjuvant therapy in invasive IPMN.

## Key findings

- Adjuvant therapy does not improve overall survival compared to follow-up in invasive IPMN patients.
- Node-positive patients show improved overall survival with adjuvant therapy.
- High heterogeneity was observed in the primary endpoint analysis.

## Abstract

This meta‐analysis aims to evaluate the efficacy of adjuvant therapy (ADJ) in patients with resected invasive IPMNs, compared with follow‐up (FUP).

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.

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).

Adjuvant therapy should not be administered indiscriminately to all patients. Node‐positive invasive IPMN seems to have an improved OS.

PROSPERO 2024 CRD42024561326

Question: What is the efficacy of adjuvant therapy in resected invasive IPMN? Findings: This meta‐analysis showed that patients with invasive IPMN do not benefit from adjuvant therapy (HR 1.21, 95% IC: 0.81−1.79). A subgroup analysis showed that node‐positive patients have an improved OS (HR 1.86; 95% CI 1.39; 2.47, p < 0.001). Meaning: Adjuvant therapy should not be administered indiscriminately to all patients. Node‐positive IPMN seems to have improved OS.