Role of Neoadjuvant Therapy for Borderline Resectable or Locally Advanced Pancreatic Cancer

Lee, Woo Jin; Woo, Sang Myung

Abstract

Surgical resection offers the only chance of cure for nonmetastatic exocrine pancreatic cancer. However, only 15 to 20 percent of patients have potentially resectable disease at diagnosis; approximately 40 percent have distant metastases, and another 30 to 40 percent have locally advanced unresectable tumors. Typically, patients with locally advanced unresectable pancreatic cancer have tumor invasion into adjacent critical structures, particularly the celiac and superior mesenteric arteries. The optimal management of these patients is controversial, and there is no internationally embraced standard approach. Therapeutic options include chemoradiotherapy or chemotherapy alone. While it is reasonable to restage and reevaluate the potential for resectability after neoadjuvant therapy, the frequency of a complete resection and long-term survival is low for patients who initially have categorically unresectable tumors. Others have disease that is categorized as "borderline resectable." While these patients are potentially resectable, the high likelihood of an incomplete resection has prompted interest in strategies to "downstage" the tumor or to increase the likelihood of a margin-negative resection prior to surgical exploration using neoadjuvant therapy. The rationale for neoadjuvant therapy is as follows. First, it is to improve the selection of patients for whom resection will not offer a survival benefit (i.e., those who rapidly progress to metastatic disease during preoperative therapy). Second, it is to increase rates of margin-negative resections, which is the major goal of surgery. Third, it is to start an early treatment of micrometastatic disease. Initial attempt at downstaging with chemotherapy, chemoradiotherapy, or a combination followed by restaging and surgical exploration in responders rather than upfront surgery is suggested.