Lymph node density as a prognostic indicator for bladder cancer survival: a systematic review and meta-analysis

Precise lymph node staging is critical for prognostic assessment in bladder cancer (BC). Lymph node density (LND), the ratio of positive to total lymph nodes, has emerged as an important prognostic marker that complements conventional TNM staging in various malignancies. We conducted a systematic review and meta-analysis to evaluate the prognostic significance of categorical and continuous LND for overall survival (OS), disease-specific survival (DSS), and disease-free survival (DFS) in BC patients undergoing radical cystectomy (RC). We searched PubMed, Scopus, Embase, and Web of Science from inception until August 11, 2025, for studies examining LND and survival outcomes in BC patients with RC. We pooled hazard ratios (HR) and 95% confidence intervals (CI) using a random-effects model. We included 58 reports with 77,029 patients. Higher LND group was associated with higher hazard of death (HR = 1.97, [95% CI: 1.71–2.26]; I²=31.17%), DSS (HR = 2.24, [95% CI: 1.71–2.92]; I²=88.17%), and DFS (HR = 1.77, [95% CI: 1.48–2.11]; I²=0%). When analyzed as continuous variables, each 1% increment in LND was associated with a 2% higher hazard of death (HR = 1.02, [95% CI: 1.01–1.02]; I²=42.80%), 1% higher hazard of disease-specific death (HR = 1.01, [95% CI: 1.00-1.02]; I²=90.61%), and 2% higher hazard of recurrence (HR = 1.02, [95% CI: 1.01–1.03]; I²=90.31%). Associations remained consistent across cut-off, cohort size, histology, and study-level chemotherapy subgroups. Most included studies were of good quality, and certainty of evidence ranged from moderate to high across outcomes. Publication bias assessment showed no evidence of significant bias. Sensitivity analyses confirmed the robustness of pooled estimates. Limitations include incomplete reporting of lymphadenectomy templates and chemotherapy details. LND is a prognostic indicator for BC patients after RC, enhancing risk stratification. Lymph node density as a prognostic indicator for bladder cancer survival: a systematic review and meta-analysis