Extracapsular Extension of Pelvic Lymph Node Metastasis is an Independent Prognostic Factor in Bladder Cancer: A Systematic Review and Meta-analysis

We aimed to elucidate the relation between extracapsular extension (ECE) and clinical outcomes in node-positive patients following radical cystectomy for bladder cancer. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we searched PubMed, SCOPUS, Web of Science, and Cochrane Library databases from their respective dates of inception until September 2014. Ten articles that met the eligibility criteria included 43-748 subjects per study, with the total number of patients being 1,893. The frequency of ECE ranged from 36.6 to 58.1 %. The pooled hazard ratio (HR) was statistically significant for recurrence-free survival (RFS) [pooled HR 1.56; 95 % confidence interval (CI) 1.13-2.14] and cancer-specific survival (CSS) (pooled HR 1.60; 95 % CI 1.29-1.99) but not overall survival (OS) (pooled HR 1.47; 95 % CI 0.71-3.05). Heterogeneity in RFS (I (2) 84 %, p < 0.00001) and OS (I (2) 80 %, p = 0.03) was statistically significant. According to subgroup analysis with meta-regression analyses, "region" (pheterogeneity < 0.0001) and "analysis results" (pheterogeneity < 0.0001) were the sources of heterogeneity. Sensitivity analysis showed that omission of any study did not lead to a significant difference. No statistical evidence of publication bias regarding RFS or CSS was revealed among the studies using Begg's and Egger's tests. This meta-analysis shows that ECE is an efficient prognostic factor for node-positive bladder cancer. However, large prospective studies are needed to confirm the clinical utility of ECE as an independent prognostic factor before these results can be applied clinically.