Survivin as a Prognostic Marker for Urothelial Carcinoma of the Bladder: A Multicenter External Validation Study

Purpose: The aim of the current study was to externally validate the value of survivin as a prognostic marker for bladder cancer in a large multi-institutional cohort of patients treated with radical cystectomy. Methods: The study comprised 726 patients treated with radical cystectomy and bilateral pelvic lymphadenectomy. Survivin staining and scoring were done with automated systems coupled with advanced color detection software. Specimens showing at least 10% reactivity were considered altered. Predictive accuracy was quantified using the concordance index and 200-bootstrap resamples were used to reduce overfit bias. Results: Survivin was an independent predictor of disease recurrence and cancer-specific survival in multivariable analyses that controlled for the effects of standard clinicopathologic features (hazard ratios, similar to 1.6; P values <= 0.002). In all patients (n = 726), addition of survivin to a model including standard clinicopathologic variables did not improve its predictive accuracy (P = 0.67 for disease recurrence and P = 0.27 for cancer-specific survival). In the subgroup of patients with pT(1-3)N(0)M(0) disease (n = 398), addition of survivin improved the accuracy of standard clinicopathologic features for prediction of disease recurrence and cancer-specific survival (1.3%, P < 0.001 and 1.2%, P < 0.001, respectively). Conclusions: Survivin expression improves our accuracy for prediction of cancer recurrence and survival in pT(1-3)N(0)M(0) patients by a small but statistically significant margin. Our findings support the need for further evaluation of survivin and its signaling pathways as well as survivin-targeted therapies in bladder cancer. (Clin Cancer Res 2009;15(22):7012-9)