Detection and Risk Stratification in Veterans Presenting With Microscopic Hematuria

This is a multicenter, observational study prospectively enrolling up to 1000 subjects with microscopic hematuria (three or more red blood cells per high powered field in one urinalysis; no visible blood in the urine) and gross hematuria (visible blood in urine) from US sites. This study will be conducted with subjects with a previous history of microscopic or gross hematuria referred to urology and scheduled for cystoscopy for the investigation of urothelial carcinoma. The study will aim to recruit an equal number of microscopic and gross hematuria patients, controlling the proportion of gross hematuria subjects recruited by targeting an approximate 1:1 ratio of microscopic to gross hematuria patients.

Consented, eligible subjects will undergo all standard of care tests as clinically indicated. In addition, one additional urine sample, using remote (at-home) or at-clinic sampling, will be collected to validate the performance characteristics for the Cxbladder Triage-Plus test. The urine sample collected from each subject will be a voided urine sample within 90 days prior to the scheduled cystoscopy or within 10 weeks post-cystoscopy.

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

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

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).

Inclusion criteria

• Subjects who are referred to urology and are either scheduled for a cystoscopy or have had a cystoscopic investigation within the last two months for the evaluation of hematuria meeting ONE of the following criteria:

EITHER: (a) Microscopic hematuria, confirmed by urine microscopy of three or more RBC/HPF (or equivalent). OR: (b) Gross hematuria.

• Physically able to provide a voided urine sample from a bladder that has not been surgically altered.
• Able to give informed, written consent.
• 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).
• Aged 18 years or older.

Footnotes:

• For the microscopic hematuria patients, the recruitment priority at each respective site will be: i) Patients who have undergone initial diagnostic cystoscopy and have been scheduled for a later TURBT for suspicious lesion in the bladder. ii) Patients who are considered high risk by the AUA 2020 guidelines.
• For gross hematuria patients, the recruitment priority at each respective site will be: i) Patients who have undergone initial diagnostic cystoscopy and have been scheduled for a later TURBT for suspicious lesion in the bladder

Exclusion criteria

• Prior history of bladder malignancy.
• Reported Cxbladder results within the last six months.
• Prior history of upper tract urothelial carcinoma (UC) or prostatic urethral UC.
• Reconstructed or diverted bladder (e.g., bladder augmentation, ileal conduit, Indiana pouch).
• Subjects aged 89 years of age or older.
• Subjects with a history of pelvic radiation.
• Subjects currently receiving systemic chemotherapy or has had systemic chemotherapy within the last six weeks.
• Subjects with renal failure on dialysis.
• History of schistosomiasis.
• Subjects who have had intervention (TURBT, diathermia, etc.,) following a previous cystoscopy.