Neoadjuvant Chemotherapy Improves Outcomes in Resectable Distal Pancreatic Adenocarcinoma

Abstract

Background: Most studies of neoadjuvant chemotherapy (NAT) for resectable pancreatic adenocarcinoma (PDAC) focus on lesions of the pancreatic head. We examined whether treatment sequence provides a survival advantage in the setting of modern systemic therapy for early stage, distal PDAC. Methods: Patients 18 years and older with clinical stage I-II PDAC involving the pancreatic body or tail who underwent curative-intent surgery from 2010-2016 were identified from the National Cancer Database. Patients were stratified by treatment regimen: NAT followed by surgery or upfront surgery +/- adjuvant chemotherapy (AT). Oncologic outcomes and overall survival were compared. Results: 4,750 patients undergoing distal or total pancreatectomy were identified. NAT led to a 33% decreased risk of positive resection margins for Stage II disease (aOR 0.67, 95%CI 0.49-0.92). The risk of positive lymph nodes at surgical resection was significantly decreased for both stages I-II (Stage I: aOR 0.64, 95%CI 0.46-0.89; Stage II: aOR 0.55, 95%CI 0.42-0.71). After inverse probability weighting to account for treatment selection bias, NAT was associated with improved OS among clinical stage II patients (median OS 2.81 years with NAT versus 2.26 years for upfront surgery +/- AT; HR 0.82, 95%CI 0.70–0.96, p=0.01). There was no difference in OS between treatment regimens for stage I patients. Conclusion: While NAT appears to confer a survival benefit only for stage II distal PDAC, NAT improves oncologic resection outcomes for patients with both stages I and II disease. Consideration for NAT should be part of multidisciplinary discussions for all early stage distal PDAC patients.