RTOG 0848: Adjuvant Chemoradiotherapy Fails Overall, but Node-Negative Patients May get benifit: JCO| June 2026

• RTOG 0848 is one of the largest randomized phase III trials evaluating the role of adjuvant chemoradiotherapy after curative-intent resection of pancreatic head adenocarcinoma.
• The study addressed a long-standing controversy in pancreatic cancer: does adding fluoropyrimidine-sensitized radiotherapy after adjuvant chemotherapy improve outcomes?
• Patients first received adjuvant gemcitabine-based chemotherapy and, if disease-free after five cycles, were randomized to receive the sixth cycle alone or combined with chemoradiotherapy.
• A total of 354 patients were randomized between chemotherapy alone and chemotherapy plus chemoradiotherapy.
• The primary endpoint was overall survival, and the study was formally negative.
• Median overall survival was similar between the two groups, and the addition of chemoradiotherapy did not significantly improve overall survival.
• Disease-free survival showed a favorable trend with chemoradiotherapy, but this did not reach conventional statistical significance.
• Importantly, adding radiotherapy did not increase grade 4 or grade 5 toxicities.
• However, grade 3 toxicity was significantly higher in patients receiving chemoradiotherapy.
• The most clinically relevant finding emerged from subgroup analysis based on lymph node status.
• Patients with node-negative disease experienced significant improvements in both overall survival and disease-free survival when chemoradiotherapy was added.
• In contrast, patients with node-positive disease did not derive a similar benefit.
• These findings suggest that local disease control may be particularly important in node-negative pancreatic cancer, whereas systemic disease biology may dominate outcomes in node-positive patients.
• The trial was conducted in the gemcitabine era, before widespread use of modern regimens such as modified FOLFIRINOX and gemcitabine-capecitabine.
• Therefore, the applicability of these findings to contemporary practice remains uncertain and requires validation in the setting of modern systemic therapy.
• The results may also support renewed interest in selective use of radiation therapy, particularly in biologically favorable patients with node-negative disease.

Bottom line: RTOG 0848 did not demonstrate an overall survival benefit for routine addition of adjuvant chemoradiotherapy after pancreatic cancer resection. However, node-negative patients showed significant improvements in survival outcomes, suggesting that carefully selected patients may still benefit from radiation as part of multimodality treatment.