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Combination of multiple molecular markers can improve prognostication in patients with locally advanced and lymph node positive bladder cancer.
- Source :
-
The Journal of urology [J Urol] 2010 Jan; Vol. 183 (1), pp. 68-75. - Publication Year :
- 2010
-
Abstract
- Purpose: We tested whether the combination of 4 established cell cycle regulators (p53, pRB, p21 and p27) could improve the ability to predict clinical outcomes in a large multi-institutional collaboration of patients with pT3-4N0 or pTany Npositive urothelial carcinoma of the bladder. We also assessed whether the combination of molecular markers is superior to any individual biomarker.<br />Materials and Methods: The study comprised 692 patients with pT3-4N0 or pTany Npositive urothelial carcinoma of the bladder treated with radical cystectomy and bilateral lymphadenectomy (median followup 5.3 years). Scoring was performed using advanced cell imaging and color detection software. The base model incorporated patient age, gender, stage, grade, lymphovascular invasion, number of lymph nodes removed, number of positive lymph nodes, concomitant carcinoma in situ and adjuvant chemotherapy.<br />Results: Individual molecular markers did not improve the predictive accuracy for disease recurrence and cancer specific mortality. Combination of all 4 molecular markers into number of altered molecular markers resulted in significantly higher predictive accuracy than any single biomarker (p <0.001). Moreover addition of number of altered molecular markers to the base model significantly improved the predictive accuracy for disease recurrence (3.9%, p <0.001) and cancer specific mortality (4.3%, p <0.001). Addition of number of altered molecular markers retained statistical significance for improving the prediction of clinical outcomes in the subgroup of patients with pT3N0 (280), pT4N0 (83) and pTany Npositive (329) disease (p <0.001).<br />Conclusions: While the status of individual molecular markers does not add sufficient value to outcome prediction in patients with advanced urothelial carcinoma of the bladder, combinations of molecular markers may improve molecular staging, prognostication and possibly prediction of response to therapy.
- Subjects :
- Adult
Aged
Aged, 80 and over
Carcinoma, Transitional Cell epidemiology
Carcinoma, Transitional Cell pathology
Carcinoma, Transitional Cell surgery
Cyclin-Dependent Kinase Inhibitor p21 analysis
Female
Humans
Lymphatic Metastasis
Male
Middle Aged
Neoplasm Invasiveness
Neoplasm Recurrence, Local epidemiology
Neoplasm Staging
Predictive Value of Tests
Prognosis
Proliferating Cell Nuclear Antigen analysis
Retinoblastoma Protein analysis
Survival Rate
Tumor Suppressor Protein p53 analysis
Urinary Bladder Neoplasms epidemiology
Urinary Bladder Neoplasms pathology
Urinary Bladder Neoplasms surgery
Biomarkers, Tumor analysis
Carcinoma, Transitional Cell chemistry
Carcinoma, Transitional Cell mortality
Urinary Bladder Neoplasms chemistry
Urinary Bladder Neoplasms mortality
Subjects
Details
- Language :
- English
- ISSN :
- 1527-3792
- Volume :
- 183
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- The Journal of urology
- Publication Type :
- Academic Journal
- Accession number :
- 19913255
- Full Text :
- https://doi.org/10.1016/j.juro.2009.08.115