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Validation of the ezrin, CK20, and Ki-67 as potential predictive markers for BCG instillation therapy of non-muscle-invasive bladder cancer
- Source :
- Urologic oncology. 35(8)
- Publication Year :
- 2016
-
Abstract
- Objective The aim of our study was to try to validate 3 promising predictive biomarkers in a database based on prospective trials comparing bacillus Calmette-Guerin (BCG) with mitomycin-C and a combination of epirubicin and interferon, respectively. Background The most common form of bladder cancer is non–muscle-invasive tumors treated initially with transurethral resection. Unfortunately more than half recur and some also progress. Consequently, an attempt to prevent poor outcome is frequently made by intravesical instillations either by chemo- or immunotherapy. The response to such treatment is unpredictable, which is why markers predicting outcome would be valuable. Patients and methods Immunohistochemical expression of ezrin, CK20, and Ki-67 was evaluated in a tumor tissue microarray based on 2 nordic multicenter trials comparing treatment with BCG vs. other intravesical adjuvant therapies. Kaplan-Meier analysis, log-rank test, and Cox regression were used to evaluate the effect of the biomarkers on recurrence-, progression-, and treatment failure-free survival. Results Of the 294 available patients immunoreactivity could be assessed in 285 patients for ezrin (97%), 285 patients for CK20 (97%), and 294 patient׳s for Ki-67 (100%). The 3 biomarkers did not predict time to any of the endpoints. Multifocality was the only predictive factor for time to recurrence ( P = 0.029) and progression ( P = 0.031). Ezrin was, however, predictive for treatment failure ( P = 0.029) in a subgroup (BCG treated in one of the trials). In a multivariate analysis among BCG treated, none of the variables correlated to recurrence and only multifocality correlated to progression. Limitations in our study are the retrospective design and those inherent to immunohistochemistry. Conclusions The negative results from this validation study question the ability of the tested biomarkers to predict therapy effect.
- Subjects :
- Oncology
Male
medicine.medical_specialty
Pathology
Urology
medicine.medical_treatment
030232 urology & nephrology
Kaplan-Meier Estimate
Keratin-20
Disease-Free Survival
03 medical and health sciences
0302 clinical medicine
Ezrin
Internal medicine
medicine
Biomarkers, Tumor
Humans
Aged
Proportional Hazards Models
Retrospective Studies
Carcinoma, Transitional Cell
Bladder cancer
biology
Proportional hazards model
business.industry
Retrospective cohort study
Immunotherapy
Middle Aged
medicine.disease
Cytoskeletal Proteins
Ki-67 Antigen
Treatment Outcome
Urinary Bladder Neoplasms
030220 oncology & carcinogenesis
Ki-67
biology.protein
BCG Vaccine
Female
business
BCG vaccine
Epirubicin
medicine.drug
Subjects
Details
- ISSN :
- 18732496
- Volume :
- 35
- Issue :
- 8
- Database :
- OpenAIRE
- Journal :
- Urologic oncology
- Accession number :
- edsair.doi.dedup.....9f7fa0325072ee003ae77dd86718d5d4