Neoadjuvant Chemotherapy Versus Upfront Surgery for Resectable Pancreatic Adenocarcinoma

Objective: To assess the association of survival with neoadjuvant chemotherapy (NAC) in resectable pancreatic adenocarcinoma (PDAC). Summary Background Data: The early control of potential micrometastases and patient selection using NAC has been advocated for patients with PDAC. However, the role of NAC for resectable PDAC remains unclear. Methods: Patients with clinical T1 and T2 PDAC were identified in the National Cancer Database from 2010 to 2017. Kaplan-Meier estimates and Cox regression models were used to compare survival. To address immortal time bias, landmark analysis was performed. Interactions between preoperative factors and NAC were investigated in subgroup analyses. A propensity score analysis was performed to compare survival between multiagent NAC and upfront surgery. Results: In total, 4,041 patients were treated with upfront surgery and 1,175 patients treated with NAC (79.4% multiagent NAC, 20.6% single-agent NAC). Using a landmark time of 6 months after diagnosis, patients treated with multiagent NAC had longer median overall survival, compared to upfront surgery and single-agent NAC. (35.8 vs. 27.1 vs. 27.4 mo). Multiagent NAC was associated with lower mortality rates compared to upfront surgery (adjusted HR, 0.77; 95% CI, 0.70–0.85), whereas single-agent NAC was not. The association of survival with multiagent NAC were consistent in analyses using the matched data sets. Interaction analysis revealed that multiagent NAC was associated with lower mortality rates across age, facility type, CA 19-9 levels, and clinical T/N stages, except in patients with body/tail tumors. Conclusion: The findings suggest that multiagent NAC followed by resection is associated with improved survival compared to upfront surgery.