Peri-operative radiotherapy for pancreatic ductal adenocarcinoma: current evidence and future directions: a narrative review.

BACKGROUND AND

OBJECTIVE

Pancreatic ductal adenocarcinoma (PDAC) carries a high risk of locoregional and distant recurrence, even after curative-intent surgery. The adoption of increasingly effective multi-agent chemotherapy, most notably modified FOLFIRINOX (mFOLFIRINOX), has shifted the focus toward understanding the incremental value of perioperative radiotherapy (RT), which remains controversial. This review aimed to summarize current evidence on the role of RT in both the adjuvant and neoadjuvant settings for resectable and borderline resectable PDAC.

METHODS

This narrative, non-systematic review synthesized randomised trials, retrospective analyses, and contemporary guidelines on peri-operative RT in PDAC. Literature from 2000-2025 was identified using PubMed and Google Scholar. Additional references were identified through manual review of bibliographies from key articles.

KEY CONTENT AND FINDINGS: The review discusses historical controversies around perioperative RT, recent evidence supporting benefit of post-operative chemoradiotherapy (CRT) in select patients, and the evolving use of RT in neoadjuvant strategies. Trials such as PREOPANC, ESPAC-5, and PRODIGE-44 are highlighted. Modern contouring atlases and planning techniques are also reviewed, emphasizing the rationale for elective coverage based on failure patterns.

CONCLUSIONS

Perioperative RT may benefit selected PDAC patients when applied within a risk-adapted framework that accounts for underlying systemic-risk biology. Ongoing work is needed to determine which clinical or biologic markers reliably identify patients most likely to benefit from RT in the setting of intensified systemic therapy.