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

Abstract

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. Cancer 2008. © 2007 American Cancer Society.

The Effectiveness of Off-Protocol Adjuvant Chemotherapy for Patients with Urothelial Carcinoma of the Urinary Bladder

“…Clearly there is a subset of patients with pathologic T 2 and node-negative disease who have occult metastasis at the time of surgery and may derive benefit from adjuvant chemotherapy. To this end, enrollment in trials such as the p53 trial, which tested the utility of adjuvant chemotherapy in patients with organ-confined (pT 1 -T 2 ) high-risk UCB based on p53 status, is strongly recommended as molecular stratification, pharmacogenetics, and/or improved imaging modalities will be necessary to tailor adjuvant therapy for these patients (22).…”

Personalized medicine in advanced urothelial cancer: when to treat, how to treat and who to treat

“…29 Similarly, Shariat and colleagues demonstrated that the addition of altered cell cycle biomarkers increased the predictive accuracy of nomogram-based disease recurrence and disease-specific survival by 10%. 30 Finally, improved characterization of the molecular pathways driving bladder cancer resulted in the identification of disease biomarkers that suggest the following therapeutic angles: mutations of fibroblast growth factor receptor 3 tyrosine kinase receptor are associated with superficial bladder cancer and a promising target for novel therapies. 38 The epidermal growth factor receptor (EGFR) pathway, associated with invasion and poor prognosis, may Advanced urothelial cancer be targeted with EGFR-family tyrosine kinase inhibitors.…”

“…Biomarkers that enhance the predictive ability of standard clinicopathologic information and optimize prognostication are being discovered. [19][20][21][22][23][24][25][26][27][28][29][30] In addition, advanced technologies offer a systematic approach for identifying active targets for drug discovery and tailored therapeutics in bladder cancer. The method described here defines a "personalized selection" approach to advanced bladder cancer within this increasingly tailored diagnostic and therapeutic framework, since optimizing management of a patient's This review explores recent advances laying the groundwork toward making "personalized selection" a reality for patients with muscle invasive and metastatic bladder cancer.…”

C5a receptor expression is associated with poor prognosis in urothelial cell carcinoma patients treated with radical cystectomy or nephroureterectomy

“…The cell cycle regulators, p53, retinoblastoma protein, p21, p27 and cyclin E1, have been reported to predict disease recurrence and mortality following radical cystectomy in patients with pTa-pT3 node-negative UCC (12). A combination of these markers exhibited significantly higher predictive accuracy for disease recurrence and cancer specific mortality compared with isolated use of the markers; however, the use of individual markers did not improve the predictive accuracy (12)(13)(14). Therefore, the identification of a novel marker that predicts survival of patients with aggressive UCC more accurately is urgently required.…”