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

Shahrokh F. Shariat, Pierre I. Karakiewicz, Raheela Ashfaq, Seth P. Lerner, Ganesh S. Palapattu, Richard J. Cote, Arthur I. Sagalowsky, Yair Lotan

Research output: Contribution to journalArticlepeer-review

170 Scopus citations


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.

Original languageEnglish
Pages (from-to)315-325
Number of pages11
Issue number2
StatePublished - Jan 15 2008


  • Bladder cancer
  • Cyclin E1
  • Immunohistochemistry
  • Recurrence
  • Retinoblastoma
  • Survival
  • p21
  • p27
  • p53


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