Elsevier

European Urology

Volume 52, Issue 3, September 2007, Pages 752-759
European Urology

Bladder Cancer
Clinical Utility of Fluorescent in situ Hybridization for the Surveillance of Bladder Cancer Patients Treated with Bacillus Calmette-Guérin Therapy

https://doi.org/10.1016/j.eururo.2007.03.001Get rights and content

Abstract

Objective

To evaluate the use of a multiprobe fluorescent in situ hybridization (FISH) assay for determining the response of patients with high-risk superficial bladder tumour (HRSBT) to bacillus Calmette-Guérin (BCG) therapy.

Methods

Bladder washing specimens from 65 HRSBT patients collected before and after BCG therapy were analyzed by FISH. Labelled probes for chromosomes 3, 7, 9, and 17 were used to assess chromosomal abnormalities indicative of malignancy.

Results

Fifty-five of 65 (85%) patients had a positive pre-BCG FISH result; 29 (45%) patients had a positive and 36 (55%) had a negative post-BCG FISH result. Patients with a positive post-BCG FISH status had a 2.7 times higher risk for tumour recurrence than patients with a negative post-BCG FISH status (p = 0.017; 95% CI: 1.18–6.15). In addition, patients who maintained a positive FISH status before and after BCG therapy had a risk for tumour recurrence 2.96 times higher than patients whose FISH result changed from positive to negative after BCG (p = 0.02; 95% CI: 1.17–7.54). On the other hand, there was no significant difference between the risk for tumour progression in patients with a positive versus a negative post-BCG FISH result (p = 0.49).

Conclusions

The high percentage of positive pre-BCG FISH results suggests the need for adjuvant therapy in patients with HRSBT after the initial transurethral resection. In addition, patients with a positive post-BCG FISH result were more likely to relapse after therapy. Thus, FISH appears to be useful for the surveillance of patients with HRSBT following BCG therapy.

Introduction

High-risk superficial bladder tumours (HRSBTs; T1, G3, multifocal or highly recurrent, carcinoma in situ [CIS]) are associated with a high recurrence and progression rate. The established initial treatment for these tumours is transurethral resection (TUR) with adjuvant bacillus Calmette-Guérin (BCG) immunotherapy [1]. However, despite this combined therapy, a high proportion of these tumours recurs or progresses to muscle-invasive disease [2]. The risk of failure of intravesical BCG may be greater than 50% in long-term follow-up, and BCG immunotherapy it is not exempt of side effects [3]. Therefore, predicting the response to BCG treatment could allow us to identify patients who are candidates for alternative therapies before recurrence or progression to muscle-invasive disease have occurred.

The UroVysion FISH assay is a multitarget test that may be performed on urine cells and detects up to four chromosomal aberrations frequently associated with bladder cancer [4]. These alterations, consisting of aneuploidy of chromosomes 3, 7, and 17 and deletion of the 9p21 locus, have been reported to have higher sensitivity than urinary cytology for detecting urothelial carcinoma in urine or bladder washing specimens [4], [5], [6], [7]. In addition, it has been suggested that this test may be useful for the detection of tumour recurrences before they are visible by cystoscopy [8]. In this study, we evaluate the use of the multiprobe FISH assay to predict the response of patients with HRSBT to BCG therapy.

Section snippets

Patient population

Sixty-five consecutive patients (8 females, 57 males; mean age: 70 yr; range: 33–86 yr) receiving BCG therapy between September 2003 and October 2004 were enrolled in this study. The hospital ethics committee approved this study, and all patients provided their informed consent before being enrolled.

Inclusion criteria for BCG therapy were primary or relapsing high-grade (HG) superficial bladder tumours with or without associated CIS (18 and 24 cases, respectively), low-grade (LG) superficial

Results

A total of 130 bladder washings were obtained from 65 patients who received BCG therapy (Table 1). During follow-up, 41 patients did not have recurrence or progression between 8.9 to 26.6 mo (mean: 16.4 mo) after the initial TUR, whereas 24 patients had tumour recurrence between 5.6 and 18.6 mo (mean: 11.6 mo) after the initial TUR. Of these patients with tumour recurrence, six presented a muscle-invasive carcinoma within a mean surveillance period of 13.3 mo (range: 9.8–18.6 mo) from the

Discussion

Although BCG therapy has been widely accepted as the optimal treatment for HRSBT after TUR, a high rate of tumour recurrence and progression has been reported after this treatment [3]. In fact, Pycha et al. [12], who first reported the influence of topical instillation therapy on chromosomal aberration in bladder cancer, noted that numerical aberrations of some chromosomes remained persistent in most cases after this immunotherapy.

Significant efforts have been made to define clinically useful

Conclusions

Our results on FISH analysis before BCG therapy in patients with HRSBT confirmed the need for an adjuvant therapy in these patients after the initial TUR. Moreover, post-BCG FISH results suggest that FISH analysis can allow the urologist to differentiate those patients with HRSBT who are more likely to relapse after BCG therapy. Thus, FISH is likely to improve the conventional surveillance techniques used after BCG therapy. In this way, HRSBT patients could be monitored more carefully and

Conflicts of interest

None of the authors has any financial arrangement with any company.

Acknowledgements

We thank Dr. Ferran Algaba for his support in the pathological analysis and Helena Kruyer for correction of the manuscript. This work was supported by the Spanish Urological Association (FIU 2004) and Fondo de Investigaciones Sanitarias (FIS 04/2630). M. Marín-Aguilera has a fellowship from Institut d’Investigacions Biomèdiques August Pi i Sunyer.

References (30)

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