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Fluorescence in situ hybridization as prognostic predictor of tumor recurrence during treatment with Bacillus Calmette-Guerin 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.

SUBMITTER: Liem EIML

PROVIDER: S-EPMC5581817 | biostudies-other | 2017 Sep

REPOSITORIES: biostudies-other

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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.

Liem Esmee I M L EIML Baard Joyce J Cauberg Evelyne C C ECC Bus Mieke T J MTJ de Bruin D Martijn DM Laguna Pes M Pilar MP de la Rosette Jean J M C H JJMCH de Reijke Theo M TM

Medical oncology (Northwood, London, England) 20170902 10

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<sup>®</sup> 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 dur ...[more]

PMID: 28866819

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Project description:BackgroundNon-muscle invasive bladder cancer (NMIBC) is known for its elevated recurrence rate, necessitating an enhancement in the current risk stratification for recurrence. The urine-based fluorescence in situ hybridization (FISH) assay has emerged as a noninvasive auxiliary tool for detecting bladder cancer. The aim of this study was to explore the potential relationship between the preoperative FISH assay and recurrence, and to develop a FISH-clinical nomogram for predicting the recurrence-free survival (RFS) in NMIBC patients.MethodsIn total, 332 eligible patients were enrolled from two hospitals. The SYSMH cohort was randomly assigned to the training set (n = 168) and the validation set I (n = 72) at a ratio of 7:3, while the SYSUTH cohort was allocated to the validation set II (n = 92). The correlation between the preoperative FISH assay and recurrence was determined through the Cox regression analysis. The least absolute shrinkage and selection operator (LASSO) Cox regression algorithm was used for model construction. The performance of the model was assessed by its discrimination, calibration, and clinical usefulness.ResultsWe uncovered that chromosome 7 aneuploidy, p16 locus loss, number of the positive FISH sites, and the FISH test result were significantly associated with tumor recurrence. Then, a FISH-clinical nomogram incorporating the FISH test result, T stage, associated CIS, tumor grade, and tumor status was developed. It showed favorable calibration and discrimination with a C-index of 0.683 (95%CI, 0.611-0.756) in the training set, which was confirmed in the validation set I and validation set II with C-indexes of 0.665 (95%CI, 0.565-0.765) and 0.778 (95%CI, 0.665-0.891), respectively. Decision curve analysis revealed the clinical usefulness of the nomogram. Moreover, our proposed nomogram significantly outperformed the guideline-recommended EORTC and CUETO scoring models.ConclusionOur study confirmed the prognostic value of the preoperative FISH assay and proposed a FISH-clinical nomogram to predict RFS in NMIBC patients. Our nomogram can serve as a more precise tool for recurrence risk stratification, which may optimize disease management in bladder cancer and improve patient prognosis.

Dataset Information

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

Publications

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.

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