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.
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.
Authors: Michael Rink; Eugene K Cha; David Green; Jens Hansen; Brian D Robinson; Yair Lotan; Arthur I Sagalowsky; Felix K Chun; Pierre I Karakiewicz; Margit Fisch; Douglas S Scherr; Shahrokh F Shariat Journal: Curr Urol Rep Date: 2012-04 Impact factor: 3.092
Authors: Randolph Stone; Anita L Sabichi; Jennifer Gill; I-Ling Lee; Patrick Adegboyega; Michael S Dai; Raja Loganantharaj; Marjan Trutschl; Urska Cvek; John L Clifford Journal: Cancer Prev Res (Phila) Date: 2010-05-25
Authors: Thomas F Chromecki; Karim Bensalah; Mesut Remzi; Grégory Verhoest; Eugene K Cha; Douglas S Scherr; Giacomo Novara; Pierre I Karakiewicz; Shahrokh F Shariat Journal: Nat Rev Urol Date: 2011-07-05 Impact factor: 14.432
Authors: Dmytro M Havaleshko; Steven Christopher Smith; HyungJun Cho; Sooyoung Cheon; Charles R Owens; Jae K Lee; Lance A Liotta; Virginia Espina; Julia D Wulfkuhle; Emanuel F Petricoin; Dan Theodorescu Journal: Neoplasia Date: 2009-11 Impact factor: 5.715