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BJU Int. 2016 May;117(5):754-60. doi: 10.1111/bju.13186. Epub 2015 Jul 3.

Novel fluorescence in situ hybridization-based definition of bacille Calmette-Guérin (BCG) failure for use in enhancing recruitment into clinical trials of intravesical therapies.

Author information

1
Department of Urology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
2
Department of Biostatistics, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
3
Department of Cytopathology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
4
Department of Epidemiology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Abstract

OBJECTIVES:

To present a molecular definition of bacille Calmette-Guérin (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.

KEYWORDS:

bacille Calmette-Guérin; bacille Calmette-Guérin failure; bladder cancer; clinical trials; fluorescence in situ hybridization

PMID:
26032953
PMCID:
PMC4666834
DOI:
10.1111/bju.13186
[Indexed for MEDLINE]
Free PMC Article

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