Fluorescence in situ hybridization as prognostic predictor of tumor recurrence during treatment with Bacillus Calmette–Guérin therapy for intermediate- and high-risk non-muscle-invasive bladder cancer

Abstract

A significant number of patients with intermediate- or high-risk bladder cancer treated with intravesical Bacillus Calmette–Guérin (BCG) immunotherapy are non-responders to this treatment. Since we cannot predict in which patients BCG therapy will fail, markers for responders are needed. UroVysion® is a multitarget fluorescence in situ hybridization (FISH) test for bladder cancer detection. The aim of this study was to evaluate whether FISH can be used to early identify recurrence during treatment with BCG. In a multicenter, prospective study, three bladder washouts at different time points during treatment (t 0 = week 0, pre-BCG, t 1 = 6 weeks following TURB, t 2 = 3 months following TURB) were collected for FISH from patients with bladder cancer treated with BCG between 2008 and 2013. Data on bladder cancer recurrence and duration of BCG maintenance therapy were recorded. Thirty-six (31.6%) out of 114 patients developed a recurrence after a median of 6 months (range 2–32). No significant association was found between a positive FISH test at t 0 or t 1 and risk of recurrence (p = 0.79 and p = 0.29). A positive t 2 FISH test was associated with a higher risk of recurrence (p = 0.001). Patients with a positive FISH test 3 months following TURB had a 4.0–4.6 times greater risk of developing a recurrence compared to patients with a negative FISH. Patients with a positive FISH test 3 months following TURB and induction BCG therapy have a higher risk of developing tumor recurrence. FISH can therefore be a useful additional tool for physicians when determining a treatment strategy.Electronic supplementary materialThe online version of this article (doi:10.1007/s12032-017-1033-z) contains supplementary material, which is available to authorized users.

The role of fluorescence in situ hybridization to predict patient response to intravesical Bacillus Calmette–Guérin therapy for bladder cancer

“…Among these records, 4 studies were reviews, and 1 study was a duplicate. Finally, data from 6 studies [ 15 – 20 ] were synthesized in this diagnostic meta-analysis (Fig. 1 ).…”

“…The difference was hypothesized that patients did not have benefitted from BCG induction therapy yet at baseline time. [ 20 , 24 ] And multiple studies [ 25 – 27 ] have reported the persistence of genetically aberrant cells after TURBT, which necessitated adjuvant therapy but not eventually progress to recurrence. Meanwhile, as the median time to recurrence after BCG reported was reported to be 26 months, [ 28 ] the median follow-up time of 16 to 23.4 months in this pooled study may not be long enough to detect all recurrences, which may also contribute to the false-positive rates.…”

Bladder cancer, a unique model to understand cancer immunity and develop immunotherapy approaches

“…However, these are general factors for poor cancer prognosis instead of predictive biomarkers. Urine cell genomic alterations detected by fluorescence in situ hybridisation during BCG treatment, although with low sensitivity , increased several fold cancer recurrence and progression risk . Next generation sequencing (NGS) is infrequently applied for BCG response prediction studies.…”

Unmasking molecular profiles of bladder cancer

“…The UroVysion test is a multicolor fluorescence in situ hybridization (FISH) assay designed to detect aneuploidy of chromosomes 3, 7, or 17, and/or the loss of the 9p21 locus [ 28 ]. A series of recent reports showed that utilization of FISH-based assay may be used as an additional tool for subclassification of patients or determining a treatment option [ 29 30 31 32 ].…”