Novel fluorescencein situhybridization-based definition of bacille Calmette-Guérin (BCG) failure for use in enhancing recruitment into clinical trials of intravesical therapies
Autor: | Graciela M. Nogueras-Gonzalez, Colin P.N. Dinney, Daniel L. Willis, H. Barton Grossman, Xifeng Wu, Rooselvelt Anderson, Rian J. Dickstein, Ruth L. Katz, Ashish M. Kamat |
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Rok vydání: | 2015 |
Předmět: |
Male
medicine.medical_specialty Urology 030232 urology & nephrology Bacille Calmette Guerin Article law.invention 03 medical and health sciences 0302 clinical medicine Randomized controlled trial law Humans Medicine Prospective Studies Treatment Failure In Situ Hybridization Fluorescence Aged Neoplasm Staging Clinical Trials as Topic Bladder cancer medicine.diagnostic_test business.industry Hazard ratio Cystoscopy medicine.disease Surgery Clinical trial Administration Intravesical Urinary Bladder Neoplasms 030220 oncology & carcinogenesis BCG Vaccine Disease Progression Female Neoplasm Grading Neoplasm Recurrence Local Bcg failure business Carcinoma in Situ Fluorescence in situ hybridization |
Zdroj: | BJU International. 117:754-760 |
ISSN: | 1464-4096 |
Popis: | Objectives To present a molecular definition of bacille Calmette-Guerin (BCG) failure that incorporates fluorescence in situ hybridization (FISH) testing to predict BCG failure before it becomes clinically evident, which can be used to enhance trial designs for patients with non-muscle-invasive bladder cancer. Patients and Methods We used data from 143 patients who were followed prospectively for 2 years during intravesical BCG therapy, during which time FISH assays were collected and correlated to clinical outcomes. Results Of the 95 patients with no evidence of tumour at 3-month cystoscopy, 23 developed tumour recurrence and 17 developed disease progression by 2 years. Patients with a positive FISH test at both 6 weeks and 3 months were more likely to develop tumour recurrence (17/37 patients [46%] and 16/28 patients [57%], respectively) than patients with a negative FISH test (6/58 patients [10%] and 3/39 patients [8%], respectively; both P < 0.001). Using hazard ratios for recurrence with positive 6-week and 3-month FISH results, we constructed clinical trial scenarios whereby patients with a negative 3-month cystoscopy and positive FISH result could be considered to have ‘molecular BCG failure’ and could be enrolled in prospective, randomized clinical trials comparing BCG therapy (control) with an experimental intravesical therapy. Conclusions Patients with positive early FISH and negative 3-month cystoscopy results can be considered to have molecular BCG failure based on their high rates of recurrence and progression. This definition is intended for use in designing clinical trials, thus potentially allowing continued use of BCG as an ethical comparator arm. |
Databáze: | OpenAIRE |
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