Borderline Resectable Pancreatic Cancer: Definitions and the Importance of Multimodality Therapy

Excerpt

The exceedingly high rates of distant metastatic recurrence following successful surgical resection of early-stage tumors would suggest that pancreatic adenocarcinoma is a systemic disease at the time of diagnosis in the vast majority of patients, and therefore a compelling case can be made for a neoadjuvant treatment approach in almost all patients. Although the first national trial of neoadjuvant therapy for resectable pancreatic cancer (ACOSOG Z5041) only recently opened, single-institution experiences have supported this form of treatment sequencing for nearly two decades. However, outside of large referral centers with disease-specific investigators committed to clinical and translational research in pancreatic cancer, confusion remains over how to define, on preoperative imaging, what is resectable and what is not (so called locally advanced or borderline resectable pancreatic cancer). In an attempt to clarify the anatomy of resectable, borderline, and locally advanced disease, Varadhachary and colleagues from the University of Texas M. D. Anderson Cancer Center proposed, in this journal in 2006, an objectively defined, computed tomography (CT)-based classification which distinguished borderline resectable from both resectable and locally advanced pancreatic cancer.1 The Varadhachary definitions considered venous abutment and encasement (without occlusion) to be resectable, in the absence of tumor extension to the celiac or superior mesenteric (SMA) arteries, as this operational definition was developed for the conduct of clinical trials of neoadjuvant treatment sequencing. There was no intent to use this definition outside of such clinical trials, and this definition of “resectable” was not intended to support a surgery-first strategy for patients who may require vascular resection and reconstruction. The Varadhachary definitions also assumed the technical capability to resect and reconstruct the superior mesenteric-portal vein (SMPV) confluence when necessary and that the major determinant of margin status (R status) was the tumor–artery (celiac, hepatic, SMA) relationship (Table 1). Katz and colleagues in 2008 reported 160 patients with borderline resectable disease (using the Varadhachary definition) treated at M. D. Anderson Cancer Center and introduced three types of borderline resectable disease, now often referred to as Katz type A, B, and C.2 Type A patients were those with borderline resectable tumor anatomy as defined in the Varadhachary manuscript. Type B patients were borderline resectable because of a concern for possible extrapancreatic metastatic disease and included those with CT findings suspicious for, but not diagnostic of, metastatic disease as well as those with known local–regional lymph node metastases. It may be reasonable in 2010 to add to this group those patients with very high carbohydrate antigen 19-9 (CA19-9) levels (measured when serum bilirubin is normal). In the future, newer biomarkers (for example, SMAD4 mutation status) may further refine patient classification in this category. Type C patients were borderline resectable due to marginal performance status or significant pre-existing medical comorbidity thought to require protracted evaluation that precluded immediate surgery. By definition, Type C patients were thought to have reversible causes of their current symptoms such as hyperbilirubinemia-induced anorexia and fatigue. Katz and colleagues provided compelling data in support of induction chemotherapy (followed by chemoradiation) for patients with borderline resectable disease. Of equal importance, they defined borderline resectable disease (with the goal of simplifying stage assignment and treatment) in all three forms which we see clinically: anatomic (local tumor anatomy), oncologic/biologic (possible advanced disease not fully apparent on imaging), and physiologic (marginal performance status). …