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

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Urothelial Carcinoma; Hematuria
• Intervention / Treatment: Diagnostic test: urine sample collection

Detailed Description

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.

• Study Type: Observational
• Enrollment (Estimated): 1000

Contacts and Locations

• Study Contact: Name: Shuxiong Zeng, M.D., Ph.D.; Phone Number: +8618930568759; Email: zengshuxiong@126.com

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200433
      • Changhai Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: N/A

• Sampling Method: Non-Probability Sample

Study Population

Patients presented with hematuria (≥ 3 RBCs/HPF) and patients with malignancy other than urothelial carcinoma in Changhai Hospital, Tongji Hospital, Renji Hospital, First Affiliated Hospital of Xian Jiaotong University, and Gulou Hospital.

Description

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:

  1. Patients recommended to undergo cystoscopy or ureteroscopy;
  2. Patients with treatment-naïve, pathology-confirmed urothelial carcinoma;
  3. 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.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Hematuria patients; 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; The level of CIN The extracted DNA from urine exfoliated cells will be analyzed by UroCAD to determine the level of CIN.
Non-hematuria patients; Patients without hematuria and diagnosed with pathology-confirmed cancer other than urothelial cancer.	Diagnostic test: urine sample collection; The level of CIN The extracted DNA from urine exfoliated cells will be analyzed by UroCAD to determine the level of CIN.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Changhai Hospital
• Collaborators: RenJi Hospital; Tongji Hospital; First Affiliated Hospital Xi'an Jiaotong University; The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School

Publications and helpful links

General Publications

• Sansregret L, Vanhaesebroeck B, Swanton C. Determinants and clinical implications of chromosomal instability in cancer. Nat Rev Clin Oncol. 2018 Mar;15(3):139-150. doi: 10.1038/nrclinonc.2017.198. Epub 2018 Jan 3.
• McDougal, W. Scott, et al. Campbell-Walsh urology 11th Edition review e-book. Elsevier Health Sciences, 2015.

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2023
• Primary Completion (Estimated): December 31, 2023
• Study Completion (Estimated): February 1, 2024

Study Registration Dates

• First Submitted: May 29, 2023
• First Submitted That Met QC Criteria: May 29, 2023
• First Posted (Actual): June 7, 2023

Study Record Updates

• Last Update Posted (Actual): June 7, 2023
• Last Update Submitted That Met QC Criteria: May 29, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: non-invasive; urothelial carcinoma; hematuria evaluation
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Urologic Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Hemorrhage; Urination Disorders; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Carcinoma, Transitional Cell; Hematuria
• Other Study ID Numbers: CH-Hematuria-CIN

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual participant data are not public for privacy protection purpose. Data without private information may be provided on request.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No