Ki-67 as a Prognostic Marker in Upper Urinary Tract Urothelial Carcinoma: A Systematic Review and Meta-Analysis

We systematically evaluated the prognostic significance of Ki-67 on survival outcomes in patients with upper urinary tract urothelial carcinoma (UTUC) treated with radical nephroureterectomy (RNU).

We searched the Embase, Scopus, and PubMed databases for all articles published up to February 2017 by following the Preferred Reporting Items for Systematic Review and Meta-analyses guidelines. The outcomes of interest included intravesical recurrence (IVR)-free survival, disease-free survival (DFS), cancer-specific survival (CSS), and overall survival (OS). The associations between Ki-67 and the survival outcomes were expressed using a pooled hazard ratio (HR) and a 95% confidence interval (CI).

A total of 12 articles, representing 1351 patients with a range from 37 to 475, met the eligibility criteria and were finally selected for this meta-analysis. The overexpression of Ki-67 was significantly associated with worse DFS (HR, 2.74; 95% CI, 1.58-4.74), CSS (HR, 2.26; 95% CI, 1.70-3.01), and OS (HR, 3.71; 95% CI, 1.78-7.75), but not IVR-free survival (HR, 0.77; 95% CI, 0.10-5.82). Interstudy heterogeneity was observed in the analysis of DFS (I² = 54%; P = .05) and IVR-free survival (I² = 81%; P = .005). The funnel plot test indicated no significant publication bias in the meta-analysis of survival outcomes.

The results drawn in this meta-analysis suggest that the overexpression of Ki-67 might be a promising prognostic indicator predicting survival outcomes after RNU for UTUC. However, a large, well designed, prospective study is necessary to establish the prognostic value of Ki-67 in UTUC.