Role of radiotherapy in surgical approaches to pancreatic cancer treatment: A narrative review

Abstract

This review discusses the evolving role of radiotherapy (RT) in the surgical treatment of pancreatic ductal adenocarcinoma (PDAC). Despite advancements in multidisciplinary treatment, PDAC continues to present significant challenges in surgical treatment strategies. Neoadjuvant therapy, in combination with chemotherapy and RT, aims to improve patient outcomes by reducing tumor size, controlling local spread, and eradicating micrometastatic disease that cannot be detected at the time of diagnosis. Recent randomized trials have shown that both neoadjuvant chemoradiotherapy (NACRT) and neoadjuvant chemotherapy (NAC) improve surgical outcomes compared with upfront surgery. A network meta-analysis integrating multiple trials demonstrated that NACRT significantly improves overall survival compared to NAC (HR: 0.79, 95% CI: 0.64-0.98). NACRT has also shown advantage in local tumor control. For locally advanced PDAC, the role of RT in conversion therapy is being actively investigated. The integration of RT in treatment regimens requires careful consideration of its therapeutic benefits against potential adverse effects. Although experimental studies suggest potential immunological benefits of RT, clinical validation remains incomplete. Recent advances in radiation delivery techniques have improved the therapeutic ratio, although further clinical validation is needed. The optimal sequence and combination of these treatment modalities with surgical strategies continue to be evaluated in ongoing clinical trials. This review synthesizes evidence from recent clinical trials and previous studies to evaluate the effectiveness, challenges, and potential of RT in PDAC treatment, aiming to inform both current clinical practice and future research directions.

Keywords: conversion surgery; neoadjuvant chemoradiotherapy; pancreatic adenocarcinoma; pancreatic surgery; radiation therapy.

FIGURE 1

Radiation therapy (RT)‐induced immune responses and abscopal effect. RT triggers the release of tumor neoantigens, leading to enhanced uptake by dendritic cells and subsequent activation of CD8+ T cells. This immune response can affect distant metastases through the abscopal effect. Furthermore, immune checkpoint inhibitors may augment such efficacy.