UroCAD for Hematuria Evaluation--A Prospective, Multi-center Study

Study Overview
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Brief Summary
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Hematuria is recognized as an important sigh of potential urinary tract malignancy. Therefore, understanding the disease processes and discovering the potential urothelial carcinoma (UC) underlying this important sign is critical. Cystoscopy, urine cytology and imaging are most reliable methods for UC diagnosis, but certain drawbacks exist for these methods, such as invasiveness or inaccuracy. Chromosomal instability (CIN) is a hallmark of human cancer, and it's related with tumor stage and grade. Previous research has proved that analyzing CIN of the DNA extracted from urothelial cells in urine samples seems a promising method for detecting UC. Here we intend to assess CIN's performance for hematuria evaluation.

Detailed Description
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Hematuria is defined as the presence of 3 or more red blood cells per high-power field (RBC/HPF) under microscopic examination of the urine, which is an important sigh of genitourinary system disease, especially UC. Several methods can be adopted for hematuria evaluation. Cystoscopy is a key component of the hematuria evaluation because it is a reliable way to evaluate the bladder and urethra. Biopsy can also be performed through cystoscopy, making it the gold standard for bladder cancer diagnosis. Despite its high reliability and accuracy, it's an invasive examination related with complications such as injury to the urethra, infection, and discomfort. Flat lesions may also be omitted under cystoscopy. Urine cytology is another important method for UC evaluation, but it has a sensitivity of only 15.8%-54.5%. CIN refers to the ongoing acquisition of genomic alterations, it can range from point mutations to small-scale genomic alterations and gross chromosomal rearrangements. 60%-80% of human tumors exhibit chromosomal abnormalities suggestive of CIN. CIN is presented in UC and it has been adopted as a diagnostic method for UC, such as UroVysion test. Previously, CIN detected by low-coverage whole genome sequencing proved to be a reliable method for UC diagnosis and was named as Urine Exfoliated Cells Copy Number Aberration Detector (UroCAD). In this prospective, multi-canter, observational clinical trial, we intend to assess the possibility of UroCAD as an additional diagnostic tool for hematuria patients by collecting and analyzing 30 ml of urine sample from hematuria patient across 5 centers.

Official Title
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Hematuria Evaluation by Whole-genome Sequencing of Urine-Exfoliated Cell DNA, A Prospective, Multi-center Study

Conditions
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Hematuria, Urothelial Carcinoma

Intervention / Treatment
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* Diagnostic Test: urine sample collection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants aged ≥ 18 years and signed informed consent form. Participants presented with hematuria (≥ 3 RBCs/HPF) and meet one of the following criteria: Patients recommended to undergo cystoscopy or ureteroscopy; Patients with treatment-naïve, pathology-confirmed urothelial carcinoma; Patients diagnosed with benign genitourinary disease. Participants diagnosed with cancer other than urothelial carcinoma. Exclusion Criteria: Participants with history of urothelial carcinoma. Participants with urothelial carcinoma accompanied by other malignancy. Individuals unwilling to sign the consent form or unwilling to provide urine sample for test or quality of urine sample is poor. Patients unsuitable for this clinical trial.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Hematuria patients<br>Hematuria patients (≥ 3 RBCs/HPF) with treatment-naïve, pathology-confirmed urothelial carcinoma or benign genitourinary system disease or with undetermined lesion presented with hematuria. | Diagnostic Test: urine sample collection<br>* The level of CIN The extracted DNA from urine exfoliated cells will be analyzed by UroCAD to determine the level of CIN.<br>|
| Non-hematuria patients<br>Patients without hematuria and diagnosed with pathology-confirmed cancer other than urothelial cancer. | Diagnostic Test: urine sample collection<br>* The level of CIN The extracted DNA from urine exfoliated cells will be analyzed by UroCAD to determine the level of CIN.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| sensitivity | Comparison of the sensitivity of the UroCAD analysis versus clinically-acceptable threshold, defined as 75%. | through study completion, an average of 8 months | 
| specificity | Comparison of the specificity of the UroCAD analysis versus clinically-acceptable threshold, defined as 95%. | through study completion, an average of 8 months | 
| Sensitivity among hematuria patients | Sensitivity of UroCAD in detecting urothelial carcinoma among hematuria patients | through study completion, an average of 8 months | 
| Specificity among hematuria patients | Specificity of UroCAD in detecting urothelial carcinoma among hematuria patients | through study completion, an average of 8 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of Sensitivity | Comparison of the sensitivity of the UroCAD analysis versus urine cytology | through study completion, an average of 8 months | 
| Comparison of Specificity | Comparison of the Specificity of the UroCAD analysis versus urine cytology | through study completion, an average of 8 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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non-invasive, urothelial carcinoma, hematuria evaluation