Ki-67 is an independent indicator in non-muscle invasive bladder cancer (NMIBC); combination of EORTC risk scores and Ki-67 expression could improve the risk stratification of NMIBC

Abstract

Objective: To prove the predicting role of Ki-67 expression and to demonstrate that the combination of European Organization for Research and Treatment of Cancer (EORTC) risk scores and Ki-67 staining status could improve the risk stratification in a large series of patients with non-muscle invasive bladder cancer (NMIBC).

Material and methods: From October 2002 to July 2010, in our cohort, 332 patients who were treated with transurethral resection of the bladder tumor were diagnosed with NMIBC by histopathologic analysis. Two experienced uropathologists rereviewed the slides. The EORTC risk scores for recurrence and progression were determined. Ki-67 expression was evaluated using immunohistochemical studies and scored for intensity and area of staining. We correlated Ki-67 expression scores with clinical and pathologic variables. We evaluated the prognosis role of EORTC risk scores, Ki-67 staining, and their combination on tumor recurrence-free survival and progression-free survival (PFS) by univariate analysis, multivariate analysis, and Kaplan-Meier survival curves.

Results: With a median follow-up of 47 (range, 2-124) months, 119 patients (35.8%) had tumor recurrence and 40 patients (12%) had tumor progression. Ki-67 positivity (Ki-67>25%) was reported in 108 tumors (32.5%), and it was significantly associated with high EORTC risk scores for both tumor recurrence and progression. In univariate analysis, multifocality, tumor size, tumor stage, tumor grade, and Ki-67 staining correlated with recurrence-free survival, whereas tumor size, tumor stage, tumor grade, concomitant CIS, and Ki-67 staining correlated with PFS. In multivariable analysis, Ki-67 expression was an independent risk factor for predicting tumor recurrence (hazard ratio, 2.14; P<0.0001) and progression (hazard ratio: 2.97, P = 0.004). Kaplan-Meier curves showed that combining EORTC risk scores and Ki-67 staining led to more accurate prediction for tumor recurrence and progression (log-rank test; P<0.0001).

Conclusions: Ki-67 positivity is prognostic for predicting tumor recurrence and progression. Combination of EORTC risk scores with Ki-67 expression could improve the risk stratification for both recurrence and progression in NMIBC.

Keywords: EORTC; Immunohistochemistry; Ki-67; Non–muscle invasive bladder cancer; Prognosis.