Impact of Neoadjuvant Therapy on Oncological Outcomes of Patients With Distal Pancreatic Adenocarcinoma

Background: Distal pancreatic ductal adenocarcinoma (D-PDAC) often presents at an advanced stage. The efficacy of neoadjuvant therapy (NAT) in improving outcomes for D-PDAC is not well-established. This study evaluates the impact of NAT on the oncological outcomes of patients with D-PDAC. Methods: A retrospective cohort study of consecutive patients with resectable and borderline-resectable D-PDAC treated at a single center from 2012 to 2020 was performed. Stratification was based on initial treatment-NAT or surgery first (SF). Survival analysis, following intention-to-treat framework, used Kaplan-Meier and Cox regression to assess NAT's impact on progression-free survival (PFS) and overall survival (OS) of D-PDAC. Results: Among 141 patients (median age 69.8 years, 51.8% females) included in the study, 71 (50.4%) received NAT and 70 (49.6%) were planned for SF. Patients receiving NAT were younger (65.9 vs. 72.6 years) and had higher incidence of borderline-resectable disease (31% vs. 4.3%) (both p < 0.05) than those undergoing SF. Thirteen patients (18.3%) undergoing NAT and five (7.1%) in SF group, failed to undergo resection. Univariate comparison showed no difference in the PFS (SF:13.97 vs. NAT:17.00 months, p = 0.6), and OS (SF:23.73 vs. NAT:32.53 months, p = 0.35). Multivariate Cox regression analysis noted significantly improved PFS (HR = 0.64, 95%CI = 0.42-0.96, p = 0.031) and OS (HR = 0.60, 95%CI = 0.39-0.93, p = 0.021) with NAT. Conclusion: NAT is associated with improved PFS and OS in patients with -D-PDAC. Further randomized controlled trials are warranted to confirm these findings.