# Perioperative Immunotherapy for Pancreatic Cancer: A Systematic Review of Randomized Controlled Trials

## TL;DR

This review examines how adding immunotherapy before and after surgery affects survival and immune responses in pancreatic cancer patients.

## Contribution

A systematic evaluation of randomized trials on perioperative immunotherapy for pancreatic cancer, highlighting survival benefits and immune activity.

## Key findings

- Three trials reported significant improvements in overall survival with perioperative immunotherapy.
- Four studies observed increased immune activity, including higher lymphocyte counts and tumor-infiltrating lymphocyte activity.
- Safety outcomes showed mixed results, with some studies reporting Grade ≥3 adverse events and others finding comparable side effects.

## Abstract

Pancreatic cancer poses a significant clinical challenge due to its aggressive nature and poor prognosis. While surgery remains the primary curative option, the emergence of immunotherapy presents a promising avenue for improving patient outcomes. This systematic review evaluates the effectiveness and safety of perioperative immunotherapy in patients with pancreatic cancer.

PubMed, Cochrane Library, and clinicaltrials.gov were searched for all relevant articles published up to July 2024. Only randomized controlled trials (RCTs) were included, and the PRISMA guidelines were followed. The primary outcome was overall survival (OS); secondary outcomes included progression-free survival (PFS), recurrence-free survival (RFS), disease-free survival (DFS), adverse events, and immune activity.

A total of six RCTs were included in this review. Among the six included trials, three reported significant improvements in OS with perioperative immunotherapy. PFS was improved in three studies, while RFS and DFS showed mixed results; only one trial reported a significant improvement in DFS. Safety outcomes varied across studies, with one study reporting Grade ≥ 3 adverse events related to immunotherapy, while two studies found that the side effects were comparable between the two groups. Notably, four studies observed increased immune activity, marked by higher lymphocyte counts and enhanced activity of tumor-infiltrating lymphocytes in the immunotherapy group.

Perioperative immunotherapy appears to be a feasible and potentially beneficial approach in pancreatic cancer, showing promise in improving survival and immune responsiveness. While findings are heterogeneous, these results support further investigation through large-scale, biomarker-driven studies to optimize its integration into perioperative management strategies.

The online version contains supplementary material available at 10.1007/s12029-026-01431-z.