Survival benefit and impact of adjuvant chemotherapy following systemic neoadjuvant chemotherapy in patients with resected pancreas ductal adenocarcinoma: a retrospective cohort study

Background: Patients with pancreatic ductal adenocarcinoma (PDAC) are increasingly receiving systemic neoadjuvant chemotherapy (NAC), particularly those with borderline resectable and locally advanced disease. However, the specific role of additional adjuvant chemotherapy (AC) in these patients is unknown. The objective of this study is to further assess the clinical benefit and impact of systemic AC in patients with resected PDAC after NAC. Methods: Data on PDAC patients with or without AC following systemic NAC and surgical resection were retrospectively retrieved from the Surveillance, Epidemiology, and End Results (SEER) database between 2006 and 2019. A matched cohort was created using propensity score matching (PSM), and baseline characteristics were balanced to reduce bias. Overall survival (OS) and cancer-specific survival (CSS) were calculated using matching cohorts. Results: The study enrolled a total of 1,589 patients, with 623 (39.2%) in the AC group and 966 (51.8%) in the non-AC group (mean age, 64.0 [9.9] years; 766 [48.2%] were females and 823 [51.8%] were males). All patients received NAC, and among the crude population, 582 (36.6%) received neoadjuvant radiotherapy, while 168 (10.6%) received adjuvant radiotherapy. Following the 1:1 PSM, 597 patients from each group were evaluated further. The AC and non-AC groups had significantly different median OS (30.0 vs. 25.0 mo, P =0.002) and CSS (33.0 vs. 27.0 mo, P =0.004). After multivariate Cox regression analysis, systemic AC was independently associated with improved survival ( P =0.003, HR=0.782; 95%CI, 0.667-0.917 for OS; P =0.004, HR=0.784; 95%CI, 0.663-0.926 for CSS), and age, tumor grade, and AJCC N staging were also independent predictors of survival. Only patients younger than 65 years old and those with a pathological N1 category showed a significant association between systemic AC and improved survival in the subgroup analysis adjusted for these covariates. Conclusion: Systemic AC provides a significant survival benefit in patients with resected PDAC following NAC compared to non-AC patients. Our study discovered that younger patients, patients with aggressive tumors and potentially well response to NAC might benefit from AC to achieve prolonged survival after curative tumor resection.