Significance of Ki-67 in non-muscle invasive bladder cancer patients: a systematic review and meta-analysis

PURPOSE: This meta-analysis evaluated the prognostic significance of Ki-67 in non-muscle invasive bladder cancer (NMIBC). MATERIALS AND METHODS: We selected 39 articles including 5,229 patients from Embase, Scopus, and PubMed searches. The primary outcomes, recurrence-free survival (RFS), progression-free survival (PFS), disease-specific survival (DSS), and overall survival (OS) were determined using time-to event hazard ratios (HRs) with 95% confidence intervals (CIs). Study heterogeneity was tested by chi-square and I(2) statistics. Heterogeneity sources were identified by subgroup meta-regression analysis. RESULTS: Two studies were prospective; 37 were retrospective. Immunohistochemistry was performed in tissue microarrays or serial sections. A wide range of antibody dilutions and Ki-67 positivity thresholds were used. Study heterogeneity was attributed to analysis results in studies of RFS (p < 0.0001). Meta-regression analysis revealed that region and analysis results accounted for heterogeneity in PFS studies (p = 0.00471, p < 0.0001). High Ki-67 expression was associated with poor RFS (pooled HR, 1.78; 95% CI, 1.48–2.15), poor PFS (pooled HR, 1.28; 95% CI, 1.13–2.15), poor DSS (pooled HR, 2.24; 95% CI, 1.47–2.15), and worse OS (pooled HR, 2.29; 95% CI, 1.24–4.22). CONCLUSIONS: The meta-analysis found that current evidence supports the prognostic value of Ki-67 in NMIBC patients.