Surgical Considerations for Neoadjuvant Therapy for Pancreatic Adenocarcinoma

SIMPLE SUMMARY: Pancreatic ductal adenocarcinoma (PDAC) is a morbid malignancy with discouraging survival rates. Enthusiasm for pre-operative therapy (chemotherapy, radiation, chemoradiation) in the treatment of PDAC has grown, with many clinical guidelines recommending its use in patients with borderline resectable tumors. The purpose of this review is to discuss important surgical considerations for the use of pre-operative therapy in patients with pancreatic cancer undergoing curative intent surgery. These considerations include accurately determining tumor resectability, vascular resection, reconstruction when tumors involve surrounding vascular structures, and implementing pre-operative fitness programs to improve treatment outcomes. We also discuss methods to evaluate the response of PDAC to pre-operative therapy such as CA 19-9 levels, imaging studies, and others that are currently being studied for potential use in the future. Preoperative therapy can provide many benefits to patients with pancreatic cancer undergoing surgery, but a comprehensive understanding of several surgical considerations is needed. ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is a challenging disease process with a 5-year survival rate of only 11%. Neoadjuvant therapy in patients with localized pancreatic cancer has multiple theoretical benefits, including improved patient selection for surgery, early delivery of systemic therapy, and assessment of response to therapy. Herein, we review key surgical considerations when selecting patients for neoadjuvant therapy and curative-intent resection. Accurate determination of resectability at diagnosis is critical and should be based on not only anatomic criteria but also biologic and clinical criteria to determine optimal treatment sequencing. Borderline resectable or locally advanced pancreatic cancer is best treated with neoadjuvant therapy and resection, including vascular resection and reconstruction when appropriate. Lastly, providing nutritional, prehabilitation, and supportive care interventions to improve patient fitness prior to surgical intervention and adequately address the adverse effects of therapy is critical.