Neoadjuvant therapy versus upfront surgery for resected pancreatic adenocarcinoma: A nationwide propensity score matched analysis

Background. Neoadjuvant therapy is an emerging paradigm in pancreatic cancer care; however, its role for resectable disease remains controversial in the absence of conclusive randomized controlled trials. The purpose of the present study is to assess the impact of neoadjuvant therapy on survival in resected pancreatic cancer patients by clinical stage. Methods. A retrospective cohort study using the National Cancer Data Base from 2004 to 2012 including nonmetastatic pancreatic adenocarcinoma patients who underwent pancreatectomy and initiated chemotherapy. Propensity score matching within each stage was used to account for potential selection bias between patients undergoing neoadjuvant therapy and upfront surgery. Overall survival was compared by the Kaplan-Meier method. Results. In the study, 1,541 and 7,159 patients received neoadjuvant therapy followed by surgery and upfront surgery succeeded by adjuvant therapy, respectively. In clinical stage III pancreatic cancer (n = 486), neoadjuvant therapy was associated with significant survival benefit after matching (median survival 22.9 vs 17.3 months; log-rank P <.0001) compared with conventional upfront surgery followed by adjuvant therapy; however, no survival difference was found between the 2 treatment sequences in patients with clinical stage I (n = 3,149; median survival, 26.2 vs 25.7 months; P =.4418) and II (n = 5,065; median survival, 23.5 vs 23.0 months; P =. 7751) disease after matching. Conclusion. The survival impact of neoadjuvant therapy is stage-dependent. Neoadjuvant therapy does not disadvantage survival compared with conventional upfront surgery followed by adjuvant therapy in any stage, and is associated with a significant survival advantage in stage III pancreatic cancer.