Article

High-risk nonmuscle invasive bladder cancer: definition and epidemiology.

Department of Urology, UCSF Helen Diller Comprehensive Cancer Center, University of California, San Francisco, California, USA.
Current opinion in urology (Impact Factor: 2.12). 07/2012; 22(5):385-9. DOI: 10.1097/MOU.0b013e328356aecf
Source: PubMed

ABSTRACT Nonmuscle invasive bladder cancer represents a large majority of patients diagnosed with this disease. Precise definition and risk stratification are paramount in this group as high-risk patients have higher rates of progression and mortality and may benefit from early identification and aggressive treatment.
The mainstay definitions of high-risk nonmuscle invasive bladder cancer are based on grade and stage. Recently, efforts have been made to incorporate other clinical variables into multivariate risk assessment tools and nomograms to predict disease behavior and guide management. Variant histology and molecular biomarkers are being explored as tools to refine risk stratification; however, results are still preliminary and need validation.
Future research should concentrate on ways to better risk-stratify patients and identify early those that are most likely to recur and progress quickly. Topics of focus should be on better multivariate risk assessment tools and nomograms providing continuous scales and incorporating molecular markers with validation in large multi-institutional cohorts.

0 Bookmarks
 · 
75 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: We compared survival after early versus delayed cystectomy in patients with high risk superficial bladder tumors. Of 307 patients with high risk superficial bladder tumors who were treated initially with transurethral resection and bacillus Calmette-Guerin (BCG) therapy 90 (29%) underwent cystectomy for recurrent tumor during a followup of 15 to 20 years. Disease specific survival distribution of these 90 patients was determined relative to the indications for and time of cystectomy. Of the 90 patients who underwent cystectomy 44 (49%) survived a median of 96 months. Of 35 patients with recurrent superficial bladder tumors 92% and 56% survived who underwent cystectomy less than 2 years after initial BCG therapy and after 2 years of followup, respectively. Of 55 patients with recurrent muscle invasive bladder disease 41% and 18% survived when cystectomy was performed within and after 2 years, respectively. Multivariate analysis showed that survival was improved in patients who underwent earlier rather than delayed cystectomy for nonmuscle invasive tumor relapse. Earlier cystectomy improves the long-term survival of patients with high risk superficial bladder tumors in whom BCG therapy fails.
    The Journal of Urology 11/2001; 166(4):1296-9. · 3.75 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Urothelial carcinoma of the bladder is unique among epithelial carcinomas in its divergent pathways of tumorigenesis. Low-grade papillary tumours rarely become muscle-invasive and they frequently harbour gene mutations that constitutively activate the receptor tyrosine kinase-Ras pathway. By contrast, most high-grade invasive tumours progress to life-threatening metastases and have defects in the p53 and the retinoblastoma protein pathways. Correcting pathway-specific defects represents an attractive strategy for the molecular therapy of urothelial carcinomas.
    Nature reviews. Cancer 10/2005; 5(9):713-25. · 37.91 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: To determine the prognostic value of a subset of regulators of the transition from G1-to-S phase of cell cycle in stage T1 grade 3 bladder cancers. Fifty-one such cases were investigated to determine the significance on patient's survival of p53, p21Waf1, p27Kip1, Cyclin D1, Cyclin D3, and ki67-MIB1 (proliferation index). The statistical analysis included Kaplan-Meier methodology with Log-rank test and Cox' proportional hazard analysis. Tumor size (p=0.0034), and the labeling index of ki67-MIB1 (p=0.0034), p53 (p=0.0332), p27kip1 (p=0.0059) and Cyclin D1 (p=0.0103) were associated to disease-free survival. Progression-free survival was related to tumor size (p<0.0001), ki67 (p=0.0163), p53 (p=0.0041), p27kip1 (p=0.0161), Cyclin D1 (p<0.0001) and Cyclin D3 (p<0.0001). Patient's overall survival was associated to Cyclin D3 (p<0.0001), p53 (p=0.0017), p21Waf1 (p=0.0142), Cyclin D1 (p<0.0001), ki67-MIB1 (p=0.0450), and tumor size (p=0.0296). Down-regulation of p27kip1 and Cyclin D3 over-expression (disease-free), over-expression of p53, Cyclin D1 and Cyclin D3 (progression-free), and over-expression of Cyclin D3 (overall survival) were independent predictors by Cox's multivariate analysis. Down-regulation of p27kip1 (p<0.001, R.R. 0.997, 95%C.I. 0.995-0.999), and over-expression of Cyclin D1 (p<0.001, R.R. 1.009, 95%C.I. 1.004-1.014) and Cyclin D3 (p=0.005, R.R. 1.013, 95%C.I. 1.004-1.022) were the main independent predictors. Down-regulation of p27kip1 and over-expression of Cyclin D1 and Cyclin D3 might be relevant predictors of survival in stage T1 grade 3 bladder cancers, thus selecting a group of patients at higher risk of malignant behavior.
    European Urology 05/2004; 45(5):606-12. · 12.48 Impact Factor