Detection and Risk Stratification in Veterans Presenting with Microscopic Hematuria

It is of current debate whether the use of invasive (referring to a process that requires insertion into the body) standard of care procedures such as a cystoscopy which is a procedure to look inside the bladder using a thin camera called a cystoscope, is appropriate for use in patients with microscopic hematuria or blood in urine invisible to the naked eye. This is because the risk of disease (bladder cancer - urothelial carcinoma) is relatively low in this population group, approximately 3%. Invasive procedures such as a cystoscopy comes with anxiety and pain, in addition to other potential side effects. This has resulted in low admittance in urology clinics for cystoscopy with hematuria (blood in urine) patients. Therefore, there is a need for a more simple, non-invasive test that can accurately detect the presence or absence of disease (urothelial carcinoma) in patients with microscopic hematuria. There is a potential role Cxbladder, a non-invasive, urine based test, can fill this role.

This is a multicenter, observational study prospectively enrolling up to 1000 subjects with microscopic hematuria from Veterans Affairs Medical Centers. This study will be conducted with subjects with a previous history of microscopic hematuria (three or more red blood cells per high powered field in one urinalysis) undergoing clinical assessment including cystoscopy. Consented, eligible subjects will undergo all standard of care tests as clinically indicated. In addition, one additional urine sample, using remote (at-home) sampling, will be collected to validate the performance characteristics for the Cxbladder Detect-plus test. The urine sample collected from each subject will be a voided urine sample at one time point prior to the scheduled cystoscopy.

The primary aim of this study is to validate the use of Cxbladder Detect-plus as an effective diagnostic tool to:

1. Enable patients with microscopic hematuria who have a low probability of having disease (urothelial carcinoma) to be ruled out from further investigation. This will avoid expensive, invasive work-up, without compromising detection of disease.
2. Allow physicians to identify subjects at high risk of disease (urothelial carcinoma)
3. Replace less sensitive urine-based tests (such as urine cytology or other urine genomic tests currently available)
4. Adjudicate atypical cytology or equivocal cystoscopy results

Cxbladder results will not be reported to the subjects or the physicians. Each subject will be required to fill in the date of sample collection in the test-request form and Cxbladder tubes. The site will fill in case-report forms in a professional manner in accordance with good clinical practice (GCP).

Eligibility Criteria:
Inclusion Criteria:

1. Subject is referred to urology and scheduled for cystoscopy for the evaluation of microscopic hematuria after recent confirmed microscopic hematuria presentation by urine microscopy of three or more RBC/HPF.
2. Physically able to provide a voided urine sample from a bladder that has not been surgically altered.
3. Able to give informed, written consent.
4. Able and willing to comply with study requirements (complete at-home urine sampling, fill in test request forms (TRFs) / tube labels and ship urine back to the central laboratory using a prepaid courier service).
5. Aged 18 years or older.

Exclusion Criteria:

1. Prior history of bladder malignancy.
2. Visible blood in the urine within the last six months (reported in subject's records and/ or during subject's interview).
3. Reported Cxbladder results within the last six months.
4. Prior history of upper tract urothelial carcinoma (UC) or prostatic urethral UC.
5. Reconstructed or diverted bladder (e.g., bladder augmentation, ileal conduit, Indiana pouch).
6. Subjects aged 89 years of age or older.
7. Subjects with a history of pelvic radiation.
8. Subjects on any current chemotherapy or have had chemotherapy within the last six weeks.
9. Subjects with renal failure on dialysis.
10. History of schistosomiasis.