This retrospective propensity score-matched cohort study evaluated whether adding preoperative radiotherapy to neoadjuvant chemotherapy (FOLFIRINOX or gemcitabine/nab-paclitaxel) improved oncologic outcomes in 800 patients undergoing curative-intent resection for pancreatic ductal adenocarcinoma at 2 high-volume centers (2015–2023), with a median follow-up of 44 months.
Adding radiotherapy improved pathologic markers (R0 resection: 85.0% vs 52.2%; node-negative disease: 61.5% vs 33.6%; pCR: 6.6% vs 4.4%), but did not improve event-free survival (HR 1.10; 95% CI 0.88–1.37; P=.38), overall survival (HR 1.02; 95% CI 0.79–1.32; P=.84), or locoregional recurrence rates (subdistribution HR 0.90; 95% CI 0.53–1.54; P=.71). Distant recurrence was the dominant first failure in both groups (~50%).
- Retrospective design with inherent selection bias, despite propensity matching. - Two-center study limits generalizability; radiotherapy techniques and doses may vary. - Patients who progressed on chemotherapy and never reached surgery were excluded, potentially enriching for favorable biology in both groups.
Adding radiotherapy to neoadjuvant chemotherapy before pancreatic resection improves pathologic response but does not translate into survival benefit — systemic control remains the priority. Routine use of preoperative radiotherapy in resectable or borderline-resectable pancreatic cancer should not be adopted outside of clinical trials.
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