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

Abstract

Ki-67 expression has been extensively investigated as a potential prognostic marker in upper tract urothelial carcinoma (UTUC). However, there were conflicting results among previous studies. As a result of the present meta-analysis, overexpression of Ki-67 showed close correlation with poor survival outcomes. Therefore, Ki-67 might be used as a valuable marker to predict prognosis of UTUC patients after surgery. Background: 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). Materials and Methods: 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). Results: 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 (I-2 = 54%; P =.05) and IVR-free survival (I-2 = 81%; P = .005). The funnel plot test indicated no significant publication bias in the meta-analysis of survival outcomes. Conclusion: 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.