Perioperative Radiation for Patients with Resectable Pancreatic Cancer: an Updated Review After the Initial RTOG 0848 Results

Abstract

Purpose: Pancreatic cancer remains one of the most lethal malignancies, with limited long-term survival despite advances in treatment strategies. While surgical resection offers the best chance for cure in localized disease, high rates of recurrence underscore the need for effective adjuvant therapies. Over four decades, the role of adjuvant chemoradiation (CRT) has been the subject of significant debate, with numerous trials yielding mixed outcomes regarding its impact on survival. Improvements in chemotherapy regimens and radiotherapy techniques have prompted renewed efforts to define the value of CRT, particularly in comparison to chemotherapy alone. The recent initial results of RTOG 0848 mark a critical milestone in this ongoing discussion, providing contemporary evidence that challenges established assumptions and refines patient selection criteria. By identifying specific subgroups-such as lymph node-negative patients-which may benefit from CRT, the trial offers clarity while highlighting the limitations of CRT in other populations.

Methods: Herein, we review prior prospective and retrospective trials that investigated the role of perioperative CRT, in particular radiation therapy, for resectable pancreatic cancer.

Results: This review examines the trajectory of research on CRT in pancreatic cancer, assesses the implications of RTOG 0848 for current clinical practice, and underscores the importance of further studies to optimize the integration of multimodal therapy in the management of this aggressive disease.

Conclusion: The combination of results from RTOG 0848 in conjunction with the results of prior prospective and retrospective trials lend support for the use of adjuvant RT for patients with both lymph node-negative and lymph node-positive disease. However, several open questions remain about the role of this therapy in select patient cohorts, and whether neoadjuvant versus advent radiation is optimal.

Keywords: CRT; Pancreatic cancer; RTOG 0848.

Figure 1.. Timeline and summary of key prospective RTCs assessing adjuvant chemoradiation therapy for resectable pancreatic cancer.

RT: radiation therapy; CRT: chemoradiation therapy; CHT: chemotherapy; Gy: Gray; Fx: fractions; C: cycles; SOC: standard of care; 5-FU: fluorouracil; Gem: Gemcitabine; OS: overall survival; LN: lymph node(s); S1: step 1; S2: step 2.

Figure 2.. Decision tree for the use of (neo)adjuvant RT in resectable pancreatic cancer based on available prospective and retrospective data at the start of 2025.

(A) Level 1 evidence supports the use of adjuvant CRT after up front surgery and adjuvant chemotherapy in lymph node negative and surgical margin negative patients based on data from RTOG 0848, while lower-level evidence support the consideration of adjuvant RT in this treatment scenario based on a collection of large retrospective studies. (B) The use of adjuvant CRT after neoadjuvant chemotherapy followed by surgical resection is based on lower level retrospective evidence and extrapolation of results from RTOG 0848. For patients who have nodal involvement or positive surgical margins after complete neoadjuvant chemotherapy decisions regarding adjuvant CRT should be based on individualized risk factors, performance status, and nodal burden of disease, noting there is very little data to support RT in this clinical scenario where there is very high risk of occult metastatic disease. (C) CRT can be considered in the neoadjuvant setting based on level 1 evidence from the PREOPANC phase III prospective randomized controlled trial.