Abstract 1193: Prospective validation of multiple biomarkers for improved clinical decision-making in patients with urothelial carcinoma of the bladder

Objectives: To prospectively assess the predictive value of a panel of biomarkers (cyclin E1, p53, p21, p27 and pRB/Ki-67) for staging of patients with urothelial carcinoma of the bladder (UCB). Methods: 174 consecutive patients treated with transurethral resection (TUR) and/or radical cystectomy (RC) for UCB were prospectively included in the study starting in January 2007. Standardized, automated immunohistochemical staining and scoring was performed. A prognostic score (PS; ≤2 altered biomarkers=Favorable; >2 altered biomarkers=Unfavorable) was defined and correlated with clinical and pathological data. Results: The study comprised of 102 RC patients and 72 TURBT cases. Unfavorable PS were noted in 36.3 % of RC cases and 16.6 % of TURBT cases matching the more advanced pathological stages of RC patients. In RC group; an unfavorable PS was significantly associated with advanced tumor stage (p=0.02), the presence of LVI (p=0.017), recurrence (p=0.02) and survival (p=0.048). In the subgroup of patients who had biomarker evaluation at TUR and then underwent RC (n=32), 75 % and 50% of the cases with unfavorable PS showed upstaging and LN involvement at RC versus 25 % and 12.5 % in cases with favorable PS. Unfavorable PS at TUR was associated with the presence of LVI (p=0.001) and LN metastasis (p=0.026). Conclusions: The preliminary analysis of our ongoing prospective trial strongly suggests that a panel of five biomarkers improves the identification of patients at risk of upstaging at RC. An unfavorable PS may identify patients who are most likely to benefit from neo-adjuvant and adjuvant chemotherapy combined with RC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1193.