The Prognostic Role of Ki-67/MIB-1 in Upper Urinary-Tract Urothelial Carcinomas: A Systematic Review and Meta-Analysis

Background: Upper urinary-tract urothelial carcinomas (UTUC) constitute 5% of urothelial malignancies. Prognostic biomarkers would allow lower risk surgical approaches for less aggressive UTUCs. One biomarkerKi-67/mindbomb E3 ubiquitin protein ligase 1 (Ki-67/MIB-1)shows promise in UTUC, but there have been conflicting findings regarding its prognostic role. The systematic review and meta-analysis aim to determine the prognostic value of Ki-67/MIB-1 in UTUC in terms of UTUC-specific mortality rate, 5-year disease-free survival, and 5-year overall survival (including disease-specific survival). Methods: A systematic review of the current literature produced 654 records. A total of 13 studies consisting of 1030 patients were finally included in the meta-analysis. Hazard ratios (HRs) with 95% confidence intervals (CI) were extracted or estimated. The individual HR estimates were combined into a pooled HR using a fixed-effects model that summed homogeneity of the individual true HRs. Results: Patients with Ki-67/MIB-1 overexpression displayed significantly higher UTUC-specific mortality rate (pooled HR: 2.14, 95% CI: 1.73-2.64; p<0.00001), significantly reduced 5-year disease-free survival (pooled HR: 2.27, 95% CI: 1.79-2.92; p<0.00001), and significantly reduced 5-year overall survival (pooled HR=1.77; 95% CI: 1.39-2.23 p<0.00001). There was significant heterogeneity detected in the UTUC-specific mortality rate meta-analysis (I-2=63%) and the 5-year disease-free survival meta-analysis (I-2=65%), but there was no significant heterogeneity detected in the 5-year overall survival meta-analysis (I-2=0%). Egger's testing showed that none of the outcomes were influenced by publication bias (p>0.05). Conclusions: Ki-67/MIB-1 overexpression shows promise as a prognostic biomarker for UTUC patients and requires further investigation.