Neoadjuvant therapy affects margins and margins affect all: perioperative and survival outcomes in resected pancreatic adenocarcinoma

Abstract

Objective: Resection margin status is an important prognostic factor in pancreatic cancer; however, previous studies suggested that neoadjuvant therapy may abrogate R1/R0 margin effect. We investigated the predictive value of neoadjuvant therapy for margin status and subsequently, its survival benefit after pancreaticoduodenectomy for pancreatic adenocarcinoma. Methods: Patients who underwent pancreaticoduodenectomy for pancreatic adenocarcinoma between 2006 and 2012 were identified from the National Cancer Database (NCDB). Multivariate logic regression analysis was utilized to examine the predictive value of neoadjuvant chemotherapy (with or without radiation) for resection margin status, prolonged hospital stay and 90-day mortality. Propensity-score matching was performed for the probability of negative margins to equalize baseline characteristics after neoadjuvant therapy. Long-term outcomes were compared using the Kaplan-–Meier method. Results: 7189 patients were identified in total; 911 (12.7%) and 6278 (87.3%) patients received neoadjuvant therapy and upfront surgery, respectively. Neoadjuvant therapy was independently predictive for or R0 margin (81.2% vs. 74.9%; OR, 1.53; p<0.001); however, neoadjuvant therapy did not correlate with prolonged hospital stay (18.4% vs. 22.0%; OR, 1.15; p=0.128) or 90-day mortality (6.4% vs. 7.3%; OR, 1.149; p=0.335). R0 margin was associated with survival benefit in both upfront surgery (median survival, 19.8.0 vs. 14.3 months; p<0.001) and neoadjuvant therapy groups (median survival, 25.0 vs. 17.8 months; p<0.001). This survival advantage remained robust after matching. Conclusion: Neoadjuvant therapy is associated with increased R0-resection rates after pancreaticoduodenectomy for pancreatic adenocarcinoma. Moreover, R0 margin status was associated with increased survival in both up-front surgery and neoadjuvant cohorts.