Official Title
A Clinical, Non-intervention Study of the Cxbladder Urine Test for the Detection of Recurrent Urinary Tract Urothelial Carcinoma
Summary:
This observational study is designed to collect urine and relevant clinical information from
patients who have a known diagnosis of bladder cancer and currently on clinically driven
surveillance. The study aims to compare the urine test to the flexible cystoscopy procedure
(which the patient is already scheduled).
Trial Description
Primary Outcome:
- Proportion of participants with bladder cancer who are correctly identified as having cancer (true positives) and no cancer (true negatives) by the Cxbladder test.
Secondary Outcome:
- Detection rates of Cx bladder test
- Comparison of Cxbladder theoretical capacity to reduce use of flexible cystoscopy for the monitoring for recurrence of urothelial carcinoma
- Comparison of the Cxbladder test and cytology test performance on the same sample
- Performance of Cxbladder test in atypical findings of cytology and cystoscopy
- Examine urinary microbiome profile in patients with urothelial cancer
There are approximately 360,000 new cases of bladder cancer diagnosed globally each year. In
addition, this disease is responsible for 145,000 deaths annually (Parkin et al 2005).
Treatments for this cancer range from transurethral resection of the bladder tumour (TURBT)
for low stage, non-invasive tumours, to the more drastic option of radical cystectomy with
pelvic lymph node dissection for those tumours that are found to have invaded into the
muscularis propria (Parekh et al 2006). Currently, the standard of care for diagnosing
bladder cancer involves a combination of flexible cystoscopy and urine cytology, which is
usually performed after the patient presents with episodes of gross hematuria. Following
these evaluations, if evidence exists that warrants further investigation for bladder cancer
a TURBT is performed and accurate staging and grading of the tumour can occur (O'Sullivan et
al 2012). For those patients who have localized disease and have bladder preservation
therapies, long term surveillance (in high grade disease this is life-long) is required to
monitor for recurrence of tumour (Sylvester et al 2006). While cystoscopy has proven to be an
accurate tool (sensitivity 80%) in the surveillance of bladder cancer, it is nonetheless a
highly invasive procedure (Jocham et al 2008). In addition, urine cytology, which has served
as the traditional adjunct to cystoscopy operates with a modest degree of sensitivity and
therefore potential to deliver false negatives where malignant cells are not seen and false
positives for bladder cancer in patients with an acute or chronically inflamed urothlelium
(Grossman et al 2005). This leaves room for the development of a diagnostic test that is able
to deliver results with the specificity of cystoscopy but without the potential for false
negatives seen with urine cytology.
Recently, studies have shown that certain genetic markers exist that accompany the occurrence
of bladder cancer and can accurately discriminate between bladder tumours and normal tissue.
These genetic markers also show promise in being able to deliver additional information
regarding the disease state of this cancer, such the stage and grade of the tumour (Dyrskjot
et al 2003; Dyrskjot et al 2005; Thykjaer et al 2001). The informative nature of these mRNA
expression profiles, along with the frequency with which tumour exfoliation into the urine
occurs, has led to the development of a urine-based test that has the potential to diagnose
and stratify bladder cancer. This urine test, known as Cxbladder Monitor, was developed by
Pacific Edge Limited and is able to perform a combinatory analysis of the expression profiles
of five genetic biomarkers (IGF, HOXA, MDK, CDC and IL8R gene expression) and two clinical
variables (whether the previous tumour was primary or recurrent and the time since the
previous tumour was resected). This test has the potential, with further testing, to produce a
consolidated diagnostic score that is able to accurately risk stratify a given patient for
recurrence of bladder cancer based on tumour characteristics. The five genetic markers include
CDC2 (a gene involved in cell cycle activity and DNA synthesis) (O'Sullivan et al 2012),
HOXA13 (transcription factor involved in morphogenesis and differentiation of the
genitourinary tract) (Scott et al 2005), IGFBP5 (affects processes such as such as
development, differentiation, and cellular survival) (Beattie et al 2006), MDK (a heparin
binding growth factor expressed during embryogenesis) (Kadomatsu et al 2004), and CXCR2 which
is expressed in neutrophils and is increased in non-malignant, inflammatory conditions. This
marker is essential as it is helpful in reducing the risk of false positive results in
patients with an inflamed urothelium (O'Sullivan et al 2012). The Cxbladder test is able to
take into account the expression of all these relevant genetic markers and analyze their
expression profiles and interactions via a 2 way linear discriminate algorithm to form a
score that is able to predict the recurrence of bladder cancer. The success of these
preliminary studies with Cxbladder show that it has a strong potential to be used as a
alternate to urine cytology and challenge cytology's routine accompaniment to cystoscopy.
More importantly, the use of Cxbladder in the surveillance patient has the potential to
decrease the frequency with which cystoscopy would need to be performed, adjudicate equivocal
cystoscopy and cytology atypia.
View this trial on ClinicalTrials.gov
