Sequence of Chemotherapy May Not Impact Survival After Resection of Pancreatic Tail Adenocarcinoma

J Surg Oncol. 2025 Jan 13. doi: 10.1002/jso.28086. Online ahead of print.

Abstract

Introduction: Pancreatic ductal adenocarcinoma (PDAC) of the body/tail is notably different than PDAC in the head of the pancreas. Surgery plus chemotherapy is known to improve outcomes for all PDAC. The sequence of this therapy is well studied in head cancers yet has never been evaluated systematically in relation to distal pancreatectomy (DP).

Methods: Patients receiving DP for PDAC and who received chemotherapy were included. Patients were compared receiving neoadjuvant systemic therapy (NAST) only, adjuvant (AST) only, both NAST + AST, and who received total neoadjuvant therapy (TNT), defined as > 24 weeks NAST before DP. PSM was performed 1:1 between AST and each other group creating quadruplets of patients for analysis. Matching factors were determined by multivariate cox-regression analysis of factors independently affecting survival. Survival was considered from diagnosis and from surgery to account for potential biases.

Results: In total, 4677 patients were selected with 400 (8.6%) receiving TNT, 536 (11.5%) NAST, 3235 (69.2%) AST, and 506 (10.8%) NAST + AST. A total of 341 quadruplets were selected after PSM. There were no differences in comorbidities, T/N-stage, retrieved or positive lymph nodes, and margin status after matching. Kaplan-Meier analysis showed no difference in median OS between the matched treatment groups (33.71 ± 2.07 vs. 35.22 ± 1.62 vs. 32.53 ± 3.31 vs. 37.88 ± 1.90, respectively; log-rank p = 0.464). Five-year OS was not different between the groups (21% vs. 18% vs. 20% vs. 25%, respectively; p = 0.501).

Conclusion: The sequence of chemotherapy and surgery did not impact survival in distal PDAC. Providers should tailor an individualized approach designed to maximize the chance of completing both treatments.