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

Abstract

Purpose: We tried to systematically evaluate 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 Embase, Scopus, and PubMed databases for all articles published up to February 2016 in line with the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) guidelines. 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 survival outcomes were expressed with pooled hazard ratio (HR) and 95% confidence interval (CI). Results: A total of 12 articles, consisting of 1,351 patients, ranging 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). Inter-study heterogeneity was observed in the analysis of DFS (I2 = 54%

p = 0.05) and IVR free survival (I2 = 81%, p = 0.005). There was no significant publication bias in the meta-analysis of survival outcome as a result of funnel plot test. Conclusions: The results drawn in this meta-analysis suggest that the overexpression of Ki-67 may be a promising prognostic indicator predicting the survival outcome after RNU for UTUC. However, a large, well-designed, prospective study is necessary to establish the prognostic value of Ki-67 in UTUC.