Neoadjuvant Therapy or Upfront Surgery for Pancreatic Cancer-To Whom, When, and How?

Area of Science:

• Surgical Oncology
• Gastroenterology
• Medical Oncology

Background:

• Management of resectable pancreatic ductal adenocarcinoma (R-PDAC) and borderline resectable pancreatic ductal adenocarcinoma (BR-PDAC) is debated.
• Neoadjuvant therapy (NAT) shows benefits in BR-PDAC, improving resectability and R0 resection rates.
• The role of NAT in R-PDAC and immunotherapy in PDAC requires further clarification.

Purpose of the Study:

• To review evidence comparing NAT with upfront surgery for pancreatic cancer.
• To determine if NAT offers a survival advantage over post-operative strategies.
• To identify clinical scenarios benefiting most from NAT.

Main Methods:

• Comprehensive narrative review of randomized controlled trials and meta-analyses.
• Systematic literature search of PubMed, Scopus, and Google Scholar up to March 2025.
• Article selection followed PRISMA guidelines.

Main Results:

• Neoadjuvant therapy (NAT) is supported as the standard of care for BR-PDAC.
• Individualized management, guided by risk stratification, is recommended for R-PDAC.
• Immunotherapy and targeted therapies are in early research phases for PDAC.

Conclusions:

• NAT is the standard of care for borderline resectable pancreatic cancer.
• Resectable pancreatic cancer management should be individualized based on risk stratification.
• The role of immunotherapy in pancreatic cancer treatment remains under investigation.