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.