Urine-DNA Biomarkers in Detecting Bladder Cancer

Detection of Bladder Cancer Using Urinary Cell-free DNA and Cellular DNA

DNA biomarkers in urine are important diagnostic and prognostic indicators for bladder cancer. Many genetic alterations have been identified in the urinary DNA. However, not all bladder tumors harbor mutations in the most commonly altered oncogenes. Thus, to reach satisfactory sensitivity and specificity a new diagnostic test should include multiple biomarkers. The investigators will conduct a prospective evaluation of a panel of mutations in urine-DNA test for the detection of urothelial bladder carcinoma in patients with gross hematuria for cystoscope.

Study Overview

• Status: Completed
• Conditions: Bladder Cancer; Urine; Diagnosis; Biomarker
• Intervention / Treatment: Diagnostic test: Next generation sequencing

Detailed Description

Urinary DNA representative of the tumour genome provide a promising resource as a liquid biopsy for non-invasive genomic profiling of urothelial bladder cancers. Voided urine samples will be collected prior to cystoscopy. Cell free DNA and cellular DNA will both be extracted and analyzed. A blood sample will be taken. In patients with bladder wall findings suspicious of cancer, a bladder wall biopsy will be taken and submitted for histopathology examination, according to clinical standard practice. Next generation sequencing will be applied and hotspots mutations in DNA from urine, blood and tumor. Logistic regression was used to analyze the association between predictor variables and bladder cancer. The investigators will confirm a couple of common mutations occured in urine-DNA and blood-derived DNA simultaneously and verify the specificity and sensitivity of individual variance or mutation combinations to establish an predictive model with optimal robustness in diagnosis of bladder cancer. Moreover, external consistency test will be performed on subsequent patients collection.

• Study Type: Observational
• Enrollment (Actual): 125

Contacts and Locations

Study Locations

• China
  • Hunan
    • Changsha, Hunan, China, 410008
      • Xiangya Hospital of Central South Univeristy

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

The patients diagnosed with suspected bladder cancer in Xiangya Hospital of Central South University from February of 2017 till the end of this study.

Description

Inclusion Criteria:

• patients with gross hematuria or other clinical sympton suspected of bladder cancer.
• male or female patients aged >= 18 years.
• available tumor tissue, urine and blood sample.
• signed informed consent form.

Exclusion Criteria:

• prior diagnosis of cancer except bladder cancer
• age under 18 years
• individuals unwilling to sign the IRB-approved consent form
• comorbidities that would prohibit or make serial urine collection and cystoscopy examine difficult or impossible.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Diagnosed Urinary Bladder Cancers; Patients who are being monitored for bladder cancer will be the experimental group to test the urine-DNA by next generation sequencing for bladder cancer biomarkers	Diagnostic test: Next generation sequencing; The obtained DNA from the urine, blood and tumor (optional) will be tested by next generation sequencing for each arm.
Non-Urinary Bladder Cancers; Patients being treated for gross hematuria will provide a negative control to provide data from testing by next generation sequencing for biomarkers in patients being treated for other diseases.	Diagnostic test: Next generation sequencing; The obtained DNA from the urine, blood and tumor (optional) will be tested by next generation sequencing for each arm.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
sensitivity of urinalysis by Urine-DNA test	number of patients "declared positive" with the Urine-DNA test among the patients actually suffering from bladder carcinoma	through study completion, an average of 8 months
specificity of urinalysis by Urine-DNA test	number of patients "declared negative" with the Urine-DNA test among the patients without bladder carcinoma	through study completion, an average of 8 months
Identification of positive urine-DNA test results with the next generation sequencing	Identification of presence of positive urine-DNA test results with the designed panel.	through study completion, an average of 8 months
Identification of urine-DNA mutations with the next generation sequencing to create an diagnosis algorithm.	Identification of presence or absence of the mutations in urine-DNA with the next generation sequencing to create an idiagnosis algorithm	through study completion, an average of 8 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
sensitivity of blood DNA test	number of patients "declared positive" with the blood-DNA test among the patients actually suffering from bladder carcinoma	through study completion, an average of 8 months
specificity of blood DNA test	number of patients "declared negative" with the blood DNA test among the patients without bladder carcinoma	through study completion, an average of 8 months
comparison of the sensitivity of the urine DNA versus blood DNA test	number of patients "declared positive" with the urine DNA test versus patients "declared positive" with the blood DNA test.	through study completion, an average of 8 months
comparison of the specificity of the urine DNA versus blood DNA test	number of patients "declared negative" with the urine DNA test versus patients "declared negative" with the blood DNA test.	through study completion, an average of 8 months

Collaborators and Investigators

• Sponsor: Xiangya Hospital of Central South University
• Collaborators: Hunan Cancer Hospital; The Third Xiangya Hospital of Central South University; Hunan Provincial People's Hospital; Central South University; Second People's Hospital of Hunan
• Investigators: Study Chair: Long Wang, M.D., Ph.D, Xiangya Hospital of Central South Univeristy

Study record dates

Study Major Dates

• Study Start (Actual): January 17, 2017
• Primary Completion (Actual): January 5, 2020
• Study Completion (Actual): January 10, 2020

Study Registration Dates

• First Submitted: February 20, 2017
• First Submitted That Met QC Criteria: February 23, 2017
• First Posted (Actual): February 28, 2017

Study Record Updates

• Last Update Posted (Actual): November 10, 2022
• Last Update Submitted That Met QC Criteria: November 7, 2022
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Keywords: Bladder cancer; Urine; Diagnosis; DNA biomarker
• Additional Relevant MeSH Terms: Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Urologic Diseases; Urinary Bladder Diseases; Urinary Bladder Neoplasms
• Other Study ID Numbers: XYURO002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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