Borderline Resectable Pancreatic Cancer: Need for Standardization and Methods for Optimal Clinical Trial Design

Abstract

Methodological limitations of prior studies have prevented progress in the treatment of patients with borderline resectable pancreatic adenocarcinoma. Shortcomings have included the absence of staging and treatment standards and pre-existing biases with regard to the use of neoadjuvant therapy and the role of vascular resection at pancreatectomy. In this manuscript, we will review limitations of studies of borderline resectable PDAC reported to date, highlight important controversies related to this disease stage, emphasize the research infrastructure necessary for its future study, and present a recently-approved Intergroup pilot study (Alliance A0201101) that will provide a foundation upon which subsequent well-designed clinical trials can be performed.

Neoadjuvant chemotherapy in borderline resectable pancreatic cancer: A case report

“…The most active regimens for advanced disease offer the best chance of achieving downstaging and systemic disease control. FOLFIRINOX regimen resulted in a statistically significant increase in OS (11.1 vs. 6.8 months; P<0.001) and RR (31.6 vs. 9.4%; P<0.001) compared with the results observed with gemcitabine in patients with metastatic disease (6). Thus, FOLFIRINOX has been incorporated in neoadjuvant trials for BRPAC and LAPAC (Table I), either alone or in combination with chemoradiation (43)(44)(45)(46)(47)(48)(49)(50)(51)(52)(53)(54)(55)(56)(57)(58)(59).…”

“…Although skill-demanding, resection is technically feasible in BRPAC, but is associated with a high risk of positive margins and, consequently, of early recurrence (6). The present case describes a patient with BRPAC who achieved pCR subsequent to neoadjuvant FOLFIRINOX, but relapsed following surgery.…”

“…There are unresolved issues with respect to the definition of BRPAC, including how much of the SMV or major visceral arteries must be surrounded on CT scan to diagnose BR or LA unresectable, or whether or not the requirement to replace a segment of vein defines resectability. SMV, SMA, celiac artery and hepatic artery involvement have been identified as an anatomic point of contention, and numerous definitions have been proposed (5)(6)(7)10). The patient in the present case was classified as BRPAC based on porto-mesenteric involvement, segmental SMV occlusion and SMA abutment.…”

Pancreatic Adenocarcinoma, Version 2.2017, NCCN Clinical Practice Guidelines in Oncology

“…An expert consensus group developed criteria to define tumor resectability so as to improve patient selection for surgery and increase the likelihood of an R0 resection. 11,127 A more restrictive definition of borderline resectable pancreatic tumors has also been described, 128 which uses degrees of contact (eg, interface between tumor and SMA measuring ≤180° of vessel wall circumference) and contour deformity/narrowing (eg, teardrop deformity in MPV or SMV) to ascribe likelihood of vascular invasion, rather than subjective terms such as abutment and impingement. The panel endorses this definition for use in clinical trials.…”

Treatment of Locally Advanced Pancreatic Ductal Adenocarcinoma

“…Early radiologic definitions deemed tumors locally advanced if abutting the celiac trunk or superior mesenteric artery or involvement of the portal vein or superior mesenteric vein [5]. Due to the heterogeneity of definitions The University of Texas MD Anderson Cancer Center, Americas Hepatopancreaticobiliary Association/Society of Surgical Oncology/Society for Surgery of the Alimentary Tract and the National Comprehensive Cancer Network have modified these definitions based on vascular involvement [6,7,8,9]. At our center, we consider locally advanced tumors as cancers with (1) no distant metastasis, (2) absence of blood flow through the SMV and/or portal vein lumen or venous involvement not amenable to reconstruction, (3) involvement of the common hepatic artery or superior mesenteric artery over >180 degrees of the vessel circumference, (4) any celiac abutment or (5) aortic or inferior vena cava invasion or encasement.…”