# Neoadjuvant Therapy for Localized Pancreatic Cancer

## TL;DR

Neoadjuvant therapy for pancreatic cancer shows promise in improving treatment delivery and outcomes, but results are mixed and more research is needed.

## Contribution

This review summarizes clinical trials on neoadjuvant therapy for localized pancreatic cancer, highlighting its potential and inconsistencies.

## Key findings

- Neoadjuvant therapy improves chemotherapy delivery and R0 resection rates.
- Survival benefits vary, with better outcomes in borderline resectable disease.
- Results are inconsistent, especially in resectable disease, requiring further large trials.

## Abstract

Pancreatic cancer is one of the deadliest cancers, largely because it is often diagnosed late and treatment options are limited. Surgery offers the only chance for cure, but many patients are unable to receive chemotherapy after surgery due to complications or slow recovery. Giving chemotherapy before surgery, known as neoadjuvant therapy, has been proposed as a way to ensure more patients receive full treatment and to better select those who may benefit from surgery. This review summarizes major clinical trials that have studied neoadjuvant treatment for patients with localized pancreatic cancer. We discuss studies comparing chemotherapy before surgery to surgery first, trials comparing different chemotherapy regimens, and trials examining the addition of radiation. Overall, while neoadjuvant therapy shows promise, results remain mixed, and further large studies are needed to define which patients benefit most from this approach.

Background/Objectives: Pancreatic ductal adenocarcinoma is an aggressive malignancy with poor long-term survival. While surgical resection followed by adjuvant chemotherapy remains the standard of care for resectable disease, a substantial proportion of patients fail to receive postoperative therapy. Neoadjuvant treatment has emerged as an alternative strategy aimed at improving delivery of systemic therapy, increasing margin-negative resections, and better assessing tumor biology. This review summarizes major clinical trials evaluating neoadjuvant approaches in resectable and borderline resectable pancreatic cancer. Methods: A narrative review of published randomized and phase II–III clinical trials was performed, focusing on studies comparing neoadjuvant therapy with upfront surgery, trials comparing different neoadjuvant chemotherapy regimens, and studies evaluating the addition of neoadjuvant radiation therapy. Ongoing phase III trials were also reviewed. Results: Multiple trials demonstrated improved rates of chemotherapy delivery and higher R0 resection rates with neoadjuvant therapy. Some studies showed survival benefits (mOS ranging from 15.7 to 37 months), particularly in borderline resectable disease. While others failed to demonstrate an overall survival advantage compared with upfront surgery, especially in resectable disease. Trials comparing different neoadjuvant regimens and those evaluating the addition of radiation have yielded largely comparable outcomes, highlighting variability in treatment response and study design. Conclusions: Current evidence supports the feasibility and safety of neoadjuvant therapy in localized pancreatic cancer; however, survival benefits remain inconsistent, especially in resectable disease. Results underscore the need for well-powered randomized trials especially in Western populations, improved patient selection, and biologic stratification to better define the optimal role of neoadjuvant therapy.