Survival outcomes of upfront surgery versus systemic therapy followed by surgery in patients with synchronous pancreatic ductal adenocarcinoma and liver metastases: A multicenter retrospective cohort study.

e16370 Background: The optimal treatment strategy for patients with synchronous pancreatic ductal adenocarcinoma with liver metastases (sPDACLM) remains uncertain, and the role of surgery in selected patients is controversial. Comparative evidence regarding survival outcomes between upfront surgery (US) and surgery following systemic therapy (SS) in this population is limited. This study aimed to compare overall survival (OS) among patients with sPDACLM treated with different therapeutic strategies and identify prognostic factors associated with survival. Methods: This multicenter retrospective cohort study included patients with sPDACLM treated at seven tertiary medical centers in China between 2017 and 2025. Patients were categorized into three groups: upfront surgery group (US), effective systemic therapy followed by surgery (E-SS), defined as achievement of partial response [PR] per RECIST 1.1 with a > 85% reduction or normalization of serum CA19-9 after systemic therapy; and ineffective systemic therapy followed by surgery (I-SS), defined as fails to achieve PR or < 85% reduction in CA19-9 after systemic therapy. The primary endpoint was OS. Results: A total of 72 patients were included, comprising 21 in the US group, 24 in the E-SS group, and 27 in the I-SS group. Baseline characteristics differed substantially among groups, with 21 of 24 covariates demonstrating a standardized mean difference (SMD) > 0.1. Kaplan–Meier analysis showed significantly improved survival in the E-SS group compared with the US group (median OS: 31.9 vs. 8.0 months; 1-year OS: 90.47% vs. 33.33%; 3-year OS: 40.50% vs. 15.23%) and the I-SS group (median OS: 17.0 months; 1-year OS: 66.62%; 3-year OS: 0%) (P < 0.0001). Univariate Cox regression identified effective systemic therapy as a favorable prognostic factor for OS (hazard ratio [HR], 0.265; 95% CI, 0.123–0.571; P < 0.001). After adjustment for clinically relevant covariates, multivariable Cox analysis confirmed that effective systemic therapy (adjusted HR [aHR] = 0.225, 95% CI: 0.099–0.512; P < 0.001) and tumors located in the pancreatic body–tail region (aHR = 0.443, 95% CI: 0.222–0.882; P = 0.03) were independently associated with prolonged OS. Sensitivity analyses yielded consistent results, supporting the robustness of the findings. Conclusions: Among patients with sPDACLM, treatment strategies incorporating systemic therapy are associated with improved survival compared with upfront surgery. Moreover, tumors arising in the pancreatic body–tail region represent an independent favorable prognostic factor. These findings support prioritizing systemic therapy in the management of sPDACLM, with subsequent surgical resection following systemic therapy offering a clinically meaningful survival benefit.