Bladder transitional cell carcinoma (B-TCC) is the fifth to seventh most prevalent carcinoma in the United States (US) or Europe. In the USA, 69,250 new cases of bladder cancer were diagnosed and an estimated 14,990 deaths occurred in 2011. Non-muscle-invasive B-TCC has the highest recurrence rate of any carcinoma. In addition, B-TCC is the most expensive carcinoma per patient between diagnosis and death, because of its 50–80 % recurrence rate. Moreover, progression from a high-grade non-muscle-invasive cancer to a muscle-invasive cancer occurs in 10–20 % of cases. In addition, bladder carcinoma is the most expensive carcinoma per patient between diagnosis and death because of its 50–80 % recurrence rate [
1].
The current standard for diagnosing B-TCC that includes the cytological examination of cells present in voided urine alone does not provide a safe screening alternative for cystoscopy because of its low sensitivity (<30 %), especially for the detection of low-grade tumors. Consequently, the standard procedure for diagnosing bladder carcinoma recurrence is flexible cystoscopy. However, as the sensitivity of cystoscopy is approximately 80 %, some tumors could escape detection, especially in the case of flat tumors (Tis), justifying the concomitant use of cytology and the development of fluorescence cystoscopy [
2]. Stenzl et al. [
3] reported that the percentage of lesions missed by standard light cystoscopy but detected using fluorescent cystoscopy ranged between 10 % (high grade) and 55 % (atypia). Moreover, in approximately 10 % of cases, B-TCC could be associated with upper urinary tract tumors, justifying a follow-up using CT-urography, especially when the cytology is positive and the cystoscopy is negative. Cystoscopy is an invasive diagnostic approach that is unpleasant for the patient, with iatrogenic risks such as infections. Consequently, the actual practice of surveillance for patients with superficial bladder cancer differs substantially from the standards recommended in clinical guidelines [
4,
5]. After resection of the primary tumor, guidelines advocate that patients undergo such procedures every 3–12 months for at least 5 years in the case of low-risk disease and for life in the case of high risk disease [
6]. A number of noninvasive tests to detect urinary non-muscle-invasive B-TCC have been developed in order to overcome the low sensitivity of cytology and to reduce the number of irrelevant cystoscopy. Current urinary biomarkers for the detection of non-muscle-invasive B-TCC have been reviewed by Tomasini et al. [
7]. ELISA tests (BTA stat, BTA TRAK and NMP-22) and cytology-based tests (ImmunoCyt/uCyt™ and UroVysion™) have obtained either Food and Drug Administration (FDA) clearance or approval [
7]. Several reports have suggested the diagnostic utility of genetic (and epigenetic) markers [
8]. Since the work of Sidranskyet al. [
9,
10] in 1996, the detection of genomic or mitochondrial DNA alterations has been able to provide early detection of B-TCC with a high sensitivity (>70 %) and specificity (>70 %). Moreover, a better understanding of the molecular pathways [
10‐
12] involved in bladder carcinogenesis has led to the development of translational molecular analyses [loss of heterozygosity (LOH), hypermethylation of CpG-islands, point mutations] for diagnostic or prognostic purposes, from DNA isolated from cells present in voided urine samples. Aberrations on the 9p, 9q and 8p chromosomal arms are the most common events identified in non-muscle-invasive B-TCC using LOH analysis or CGH-arrays [
13]. Currently, it is generally recognized that FGFR3 gene mutations and low chromosomal instability are associated with non-aggressive superficial tumors and that high chromosomal instability and TP53 mutations drive progression to invasive carcinoma. Commercial tests have been developed based on cells present in voided urine samples or the analysis of their DNA. The FDA-approved test (Urovysion™) is based on the detection of aneuploidy for chromosomes 3, 7, and 17 and loss of the 9p21 locus. We and others have previously shown that the detection of recurrent bladder cancer can be improved by DNA analysis (LOH and DNA CpG-island hypermethylation) from voided urine. More recently, we have developed a specific and inexpensive CGH-array [
14] that combines diagnostic and prognostic performance for use in clinical practice. The array covers, with a high density, the target loci reported to be frequently gained or deleted in bladder carcinoma and, with a low density, the entire genome. The aim of this study was to measure the diagnostic performance of this urinary marker test to predict positive cystoscopy during the follow-up of non-invasive B-TCC and to assess its performance in order to identify patients with a risk of high-grade disease.