Abstract
PurposeThis meta-analysis evaluated the prognostic significance of Ki-67 in non-muscle invasive bladder cancer (NMIBC).Materials and MethodsWe 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 I2 statistics. Heterogeneity sources were identified by subgroup meta-regression analysis.ResultsTwo 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).ConclusionsThe meta-analysis found that current evidence supports the prognostic value of Ki-67 in NMIBC patients.
Highlights
Bladder cancer is the ninth most common cancer worldwide
This meta-analysis evaluated the prognostic significance of Ki-67 in non-muscle invasive bladder cancer (NMIBC)
Study heterogeneity was attributed to analysis results in studies of recurrence-free survival (RFS) (p < 0.0001)
Summary
Bladder cancer is the ninth most common cancer worldwide. 430,000 patients are diagnosed and 165,000 patients die from it annually [1]. 25% of newly diagnosed cases are muscle invasive bladder cancer (MIBC, ≥ T2), and radical cystectomy is the standard treatment. Other non-muscle invasive bladder cancers (NMIBCs) include stage Ta noninvasive papillary carcinomas and stage T1 tumors that invade the subepithelial connective tissue. The gold standard treatment of NMIBC is transurethral resection of bladder tumor (TURBT) and intravesical Bacillus Calmette–Guérin (BCG) installation. 30%–70% of patients experience a recurrence after initial treatment, and 25%–60% progress to MIBC
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