Multiple biomarkers improve prediction of bladder cancer recurrence and mortality in patients undergoing cystectomy

BACKGROUND. Tested was whether the assessment of 5 established bladder cancer biomarkers (p53, pRB, p21, p27, and cyclin E1) could improve the ability to predict disease recurrence and cancer-specific survival after radical cystectomy in patients with pTa-3N0M0 urothelial carcinoma of the bladder (UCB). METHODS. The study comprised 191 patients with pTa-3N0M0 UCB treated with radical cystectomy and bilateral lymphadenectomy (median follow-up, 3.1 years). Biomarker expression was assayed on serial tissue microarray slides using quantitative immunohistochemistry using advanced cell imaging and color detection software. Predictive accuracy was quantified using the concordance index and 200-bootstrap resamples were used to reduce overfit bias. Bootstrap-adjusted predictive accuracy estimates were compared using the Mantel-Haenszel test. RESULTS. UCB recurred in 36 (18.8%) patients and 30 (15.7%) died of bladder cancer; 157 (82.2%) patients had altered expression of at least 1 biomarker. In univariate analyses the number of altered biomarkers had the highest predictive accuracy for both disease recurrence (76.8%, P < .001) and cancer-specific mortality (78.3%, P < .001). Addition of the number of altered biomarkers increased the predictive accuracy of nomograms based on the TNM staging system for disease recurrence and cancer-specific mortality by 10.9% (83.4% vs 72.5%, P < .001) and 8.6% (86.9% vs 78.3, P < .001), respectively. CONCLUSIONS. Assessment of the number of altered biomarkers in the cystectomy specimen improves the prediction of bladder cancer recurrence and survival in patients with pTa-3N0M0 disease. Prospective evaluation of alteration in these biomarkers can help identify patients who would benefit from adjuvant treatment after radical cystectomy.