Impact of adding recurrence/metastasis-directed therapy to systemic therapy in postoperative recurrent or metastatic pancreatic adenocarcinoma: a retrospective cohort study

Background: Systemic therapy is standard treatment for postoperative recurrent or metastatic pancreatic adenocarcinoma, yet survival remains poor. While recurrence/metastasis-directed therapy (RDT/MDT) has shown benefits in other cancers, its role in pancreatic adenocarcinoma remains controversial. Objectives: To evaluate whether adding RDT/MDT can enhance the efficacy of systemic therapy in patients with postoperative local recurrence or metastasis in pancreatic adenocarcinoma. Methods: Patients with recurrence or metastasis of pancreatic adenocarcinoma following R0 resection between 2018 and 2024 at West China Hospital and Shang Jin Hospital were retrospectively enrolled. Patients were categorized into the RDT/MDT plus systemic therapy group versus the systemic therapy alone group. Propensity score matching (PSM; 1:1) was used to minimize selection bias. Survival outcomes were analyzed using Cox regression, with subgroup analyses based on postoperative recurrence/metastasis status. Clinical features and overall survival (OS) of patients receiving radiotherapy as RDT/MDT were also evaluated. Results: < 0.05). Subgroup analyses revealed significant survival advantages with RDT/MDT in patients with locoregional recurrence and widespread metastasis. In addition, a single-arm analysis of 64 patients who received radiotherapy as RDT/MDT (from the pre-PSM cohort) demonstrated a median OS of 20.1 months (95% CI: 17.5-28.5), with superior outcomes observed when radiotherapy was administered as first-line treatment. Conclusion: This study suggested that adding RDT/MDT to systemic therapy may improve OS in pancreatic adenocarcinoma with postoperative recurrence and metastasis, with radiotherapy as a feasible option. Further randomized controlled trials are warranted. Design: A multicenter, retrospective cohort study using PSM.