Non-metastatic Pancreatic Cancer: Resectable, Borderline Resectable, and Locally Advanced-Definitions of Increasing Importance for the Optimal Delivery of Multimodality Therapy

There is an evolving recognition that pancreatic cancer is a systemic disease at the time of diagnosis, even among patients with apparent localized disease. As a result, and supported by recent data demonstrating improved overall survival for patients who are treated with multimodality therapy as compared to surgery alone, greater attention has been focused on the optimal treatment sequencing of chemotherapy, chemoradiation, and surgery for patients with localized pancreatic cancer. Inherent in the decision to deliver all three modalities (or even just chemotherapy and surgery) to a patient with localized pancreatic cancer is the accurate identification of those who have potentially resectable disease at the time of diagnosis. Historically, resectability was determined at the time of operation; if the surgeon felt the tumor was resectable, the tumor was removed (often with a positive margin?) and the patient was declared to have had resectable disease. If at the time of operation the tumor was felt not to be resectable, the patient was declared to have locally advanced disease. In contrast, in order to conduct a clinical trial of neoadjuvant therapy, a pre-operative definition of resectable was needed to identify eligible patients for trial enrollment. This marked the first time that radiographic imaging (computed tomography [CT]) was used to preoperatively define and stage pancreatic cancer. The benefit of such an objectively defined staging system for patients and physicians is obvious—the goals of therapy can be specifically defined at the time of diagnosis, once staging is completed. The goals of patients (and their treating physicians) who receive neoadjuvant treatment sequencing are eventual surgery and the potential for cure. To the extent that surgery is necessary (albeit usually not sufficient) for cure, patients who may be eligible for potentially curative surgery can be accurately defined; and those patients with locally advanced (nonoperable) disease are also identified. Among patients who have locally advanced pancreatic cancer as defined by preoperative imaging, surgery has historically been felt not to be possible. However, it soon became clear that a gray-zone existed between the definitions of resectable and locally advanced pancreatic cancer. Borderline resectable disease was used to define those patients with arterial abutment and short segment venous (superior mesenteric–portal vein [SMVPV]) occlusion who, in the past, would have been considered locally advanced. However, after neoadjuvant therapy, such patients with responding disease (clinical benefit, improved imaging, and a decline in tumor marker profile) were being considered for surgery—hence the development of the borderline classification. Patients with borderline resectable pancreatic cancer are different from those with resectable disease in that they: (1) are at the highest possible risk for a positive margin of resection due to tumor–artery abutment, (2) require a more complex operation usually involving vascular resection and reconstruction; and (3) may be at higher risk for harboring radiographically occult distant metastatic disease. For these reasons, a longer period of induction therapy, often including chemotherapy followed by chemoradiation has been applied to this patient population. The chemoradiation portion of induction therapy is thought to be particularly important for those patients with arterial abutment in the hope of sterilizing at least the periphery of the tumor and thereby preventing a positive margin of resection. Society of Surgical Oncology 2015