Lymph node density as a prognostic variable in node-positive bladder cancer: A meta-analysis

Background: Although lymph node (LN) status and the LN burden determine the outcome of bladder cancer patients treated with cystectomy, compelling arguments have been made for the incorporation of LN density into the current staging system. Here, we investigate the relationship between LN density and clinical outcome in patients with LN-positive disease, following radical cystectomy for bladder cancer. Methods: PubMed, SCOPUS, the Institute for Scientific Information Web of Science, and the Cochrane Library were searched to identify relevant published literature. Results: Fourteen studies were included in the meta-analysis, with a total number of 3311 patients. Of these 14 publications, 6 studies, (533 patients), 10 studies (2966 patients), and 5 studies (1108 patients) investigated the prognostic association of LN density with disease-free survival (DFS), disease-specific survival (DSS), and overall survival (OS), respectively. The pooled hazard ratio (HR) for DFS was 1.45 (95 % confidence interval [CI], 1.10-1.91) without heterogeneity (I²=0 %, p=0.52). Higher LN density was significantly associated with poor DSS (pooled HR, 1.53; 95 % CI, 1.23-1.89). However, significant heterogeneity was found between studies (I²=66 %, p=0.002). The pooled HR for OS was statistically significant (pooled HR, 1.45; 95 % CI, 1.11-1.90) without heterogeneity (I²=42 %, p=0.14). The results of the Begg and Egger tests suggested that publication bias was not evident in this meta-analysis. Conclusions: The data from this meta-analysis indicate that LN density is an independent predictor of clinical outcome in LN-positive patients. LN density may be useful in future staging systems, thus allowing better prognostic classification of LN-positive bladder cancer.