Urine-DNA Biomarkers in Detecting Bladder Cancer

Study Overview
=================
Brief Summary
-----------------
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.

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.

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

Conditions
-----------------
Bladder Cancer, Biomarker, Diagnosis, Urine

Intervention / Treatment
-----------------
* Diagnostic Test: Next generation sequencing


Participation Criteria
=================
Eligibility Criteria
-----------------
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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Diagnosed Urinary Bladder Cancers<br>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<br>* The obtained DNA from the urine, blood and tumor (optional) will be tested by next generation sequencing for each arm.<br>|
| Non-Urinary Bladder Cancers<br>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<br>* The obtained DNA from the urine, blood and tumor (optional) will be tested by next generation sequencing for each arm.<br>|

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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Bladder cancer, Urine, DNA biomarker, Diagnosis