Contemporary Advances, Evidence, and Considerations in Preoperative Therapy for Pancreatic Ductal Adenocarcinoma

Localized pancreatic ductal adenocarcinoma (PDAC) has been historically associated with poor disease control outcomes following surgical resection alone. Due to the high risk of occult locoregional and distant metastatic disease and anatomic tumor complexity limiting margin-negative resectability, preoperative therapy has emerged as an appealing strategy for many patients across the spectrum of localized PDAC. Here, we critically review the context, evidence, and controversies regarding preoperative therapy for PDAC. We first discuss the natural history of PDAC, patterns of spread and postoperative therapy. We then consider current issues of resectability, patient selection, therapy sequencing, and specifically the role of radiation therapy, including chemoradiation and stereotactic body radiation therapy, in the preoperative paradigm respectively. We conclude by discussing ongoing trials attempting to provide further insights and illuminating the path towards the improvement of outcomes in this patient population.