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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(s) -
Kamat Ashish M.,
Willis Daniel L.,
Dickstein Rian J.,
Anderson Rooselvelt,
NoguerasGonzález Graciela,
Katz Ruth L.,
Wu Xifeng,
Barton Grossman H.,
Dinney Colin P.
Publication year - 2016
Publication title -
bju international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.773
H-Index - 148
eISSN - 1464-410X
pISSN - 1464-4096
DOI - 10.1111/bju.13186
Subject(s) - medicine , cystoscopy , bladder cancer , clinical trial , hazard ratio , fluorescence in situ hybridization , randomized controlled trial , urothelial cancer , oncology , cancer , surgery , urinary system , confidence interval , biochemistry , chemistry , chromosome , gene
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.