Outcomes of systemic therapy followed by surgery for synchronous liver metastases from pancreatic cancer: A multicenter retrospective cohort study.

e16365 Background: The role of surgical intervention in pancreatic ductal adenocarcinoma with synchronous liver metastases (sPDACLM) remains controversial. While systemic therapy is the mainstay, select patients demonstrating significant response may benefit from surgery. This study aimed to identify optimal criteria for selecting patients with sPDACLM for conversion surgery. Methods: This multicenter, retrospective cohort study analyzed patients with sPDACLM from seven Chinese centers (2017-2025). Key inclusion criteria were age ≥18, ECOG 0-1, biopsy-proven PDAC with liver metastases, and completion of ≥4 cycles of first-line systemic therapy. Patients were stratified by primary tumor resectability into an "Intention-to-Conversion Surgery (ITCS)" group (resectable/borderline resectable primary tumor) and a "Maintenance Therapy" group (unresectable primary tumor). Treatment response was assessed radiographically (RECIST 1.1 Partial Response [PR]) and biochemically (CA19-9 decline > 85% or normalization); patients meeting both criteria were classified as "Dual Responder." The primary endpoint was overall survival (OS). Results: Of 175 eligible patients, 135 were in the ITCS group and 40 in the maintenance therapy group. The median OS for the entire cohort was 13 months. The ITCS group had significantly longer median OS than the maintenance therapy group (14.0 vs. 11.4 months, P = 0.015). Multivariate analysis confirmed biochemical response, radiographic response, and baseline neutrophil-to-lymphocyte ratio (NLR) as independent prognostic factors for OS. "Dual responder" (n = 46/175, 26.3%) had a significantly superior median OS of 23.0 months compared to 11.0 months in non-responders (P < 0.001). Within the ITCS group (n = 135), "Dual responder" (n = 46, 34.1%) achieved a median OS of 24.8 months versus 11.0 months in non-responders (P < 0.001). Among these 46 "Dual responder," those who underwent surgery (n = 22) had a significantly longer median OS than those who did not (31.9 vs. 18.0 months, P = 0.05), with a 5-year survival rate of 19%. In contrast, for patients not meeting the dual criteria (n = 89), surgery did not confer a significant long-term OS benefit despite potential short-term improvement. Conclusions: The "Dual response" criteria—combining radiographic partial response (RECIST 1.1 PR) and a major biochemical response (CA19-9 decline > 85% or normalization)—effectively identifies a subgroup of patients with sPDACLM who may derive significant survival benefit from conversion surgery. Surgical intervention is not recommended for patients who fail to meet these dual criteria. These findings provide a practical framework for patient selection in the multimodal management of pancreatic ductal adenocarcinoma with synchronous liver metastases.