Chapter 139: Clinical and Pathologic Staging for Pancreatic Cancer

INTRODUCTION

Cancer staging systems have been designed to provide both physicians and patients with a metric for assessing the extent of disease and prognosis. Staging systems provide a universal classification that describes the extent of disease. This classification impacts individual stage-specific treatment, the development of practice guidelines, and the design of clinical research/trials. Cancer staging is therefore the foundation on which all clinical cares are based and is essential for the rigorous study of cancer therapies.

For most cancers, staging is predicated on the pathologic (postoperative) assessment of the tumor which is dependent on gross and histologic findings from the surgical specimens. For cancers in which presurgical (neoadjuvant) therapy is utilized, an additional clinical (preoperative) staging system is required. In pancreatic cancer, the clinical stage is determined by the biochemical, radiographic, and physical examinations of the patient, and is defined by the tumor–vasculature relationship. The accuracy of clinical staging has revolutionized the management of pancreatic cancer, which historically used operative staging to determine resectability. Prior to the use of modern imaging techniques, up to 30% of patients with presumed resectable pancreatic cancer were found, at the time of operation, to have either metastatic disease or vascular invasion which precluded resection of the pancreatic tumor.¹ The limitation of operative staging is that patients who have advanced unresectable disease experience a delay in the receipt of the best appropriate therapy (chemotherapy and/or chemoradiation) secondary to the surgical procedure and the necessary postoperative recovery. In addition, laparotomy may potentially negatively impact the tumor–host relationship in favor of tumor progression, as the effect of surgery has been associated with relative immune compromise.

In pancreatic cancer, the use of neoadjuvant therapy is an alternative to a surgery-first approach for localized disease. Neoadjuvant therapy provides systemic therapy earlier in the treatment sequence and is the preferred approach in patients with borderline resectable or locally advanced disease.² Even among patients with early-stage (resectable) pancreatic cancer who receive curative resections, the high rate of disease recurrence suggests that radiographically occult disease exists at the time of surgery in most patients. Although multiple randomized controlled trials^3-5 have demonstrated a survival benefit for patients who receive adjuvant systemic chemotherapy after pancreatectomy, at least 50% of patients fail to recover from surgery to complete adjuvant therapy.⁶ Additional advantages of a neoadjuvant strategy include (1) early treatment of presumed micrometastatic disease, (2) the ability to minimize stage misclassification by providing a time interval during which indeterminate lesions (which may be metastases) may be better characterized through serial radiographic imaging, and (3) the theoretical efficacy of radiation in nonhypoxic environment.

For pancreatic cancer, a clinical staging system has been developed that uses precise, objective, anatomic criteria to determine the extent of the tumor–vasculature relationship and guides the selection of neoadjuvant therapy. Clinical/radiographic staging performed prior to any therapy and over serial time points can provide important insights into tumor biology, ...