OBJECTIVES: The impact of lymph node dissection (LND) on the efficacy of pembrolizumab in patients with urothelial carcinoma (UC) who develop metastasis after surgery remains unclear. This study aimed to investigate the efficacy of pembrolizumab in patients with metastatic UC who underwent primary tumor resection with LND. PATIENTS AND METHODS: This retrospective study included patients who initially underwent radical surgery with or without LND for non-metastatic UC and later received pembrolizumab for recurrent lesions. Data were collected from a retrospective nationwide Japanese cohort study in patients with metastatic UC treated with pembrolizumab. The primary endpoints were overall response rate (ORR) and overall survival (OS). Multivariate analysis was performed to identify predictors of OS. RESULTS: A total of 393 patients (273 [69.5%] underwent LND, and 120 (30.5%) did not) were included in this study. The ORRs for patients with and without LND were 30.8% and 27.3%, respectively (p = 0.460). No significant difference in OS was observed between the two groups (p = 0.471). Multivariate Cox regression analysis revealed that a neutrophil-to-lymphocyte ratio ≥3.0, Eastern Cooperative Oncology Group performance status ≥2, hemoglobin <
11, and liver metastasis were associated with worse OS. However, LND was not associated with OS. CONCLUSIONS: LND during primary tumor resection did not affect the efficacy of pembrolizumab in patients with metastatic UC.