Efficacy and Utility of Cxbladder Tests in Hematuria Patients

Study Overview
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Brief Summary
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Prospective observational study to validate the performance characteristics and clinical utility of Cxbladder tests in a Veterans Affairs cohort.

Detailed Description
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Non-invasive, voided urine sample used for both Cxbladder molecular tests, voided urine sample may be used for standard of care testing. Retrospective analysis of data after study completion ensures a de-phasing of study sample analysis from clinical decision making; patient treatment and management. The study aims to sequentially recruit up to 1000 patients presenting for assessment of hematuria (microscopic or macroscopic) by cystoscopy across multiple Veterans Affairs sites

Official Title
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An Observational Study of Efficacy and Utility of Cxbladder Tests in the Identification of Low vs High Risk Patients and the Detection of Urothelial Carcinoma in Patients Presenting With Hematuria

Conditions
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Hematuria, Urothelial Carcinoma

Intervention / Treatment
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* Diagnostic Test: Cxbladder


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient is undergoing investigation of recent confirmed hematuria (by either flexible or rigid cystoscopy/TURBT), including hematuria patients referred due to suspicious/positive imaging, in order to determine the presence of urothelial carcinoma. Able to provide a voided urine sample of the required minimum volume Able to give written consent Able and willing to comply with study requirements Aged 18 years or older Exclusion Criteria: Prior history of bladder malignancy, prostate or renal cell carcinoma Prior genitourinary manipulation (flexible or rigid cystoscopy / catheterisation, urethral dilation) in the 14 days before urine collection Previous alkylating based chemotherapy Known Pregnancy.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| patients with hematuria undergoing investigation for UC<br>Patients will be recruited from those presenting with hematuria and undergoing investigative cystoscopy for the determination of possible urothelial carcinoma. This includes patients referred via imaging or from other departments for assessment of hematuria. Microscopic hematuria is defined as > 3 red blood cells per high-powered microscopy field for a properly collected urine sample. | Diagnostic Test: Cxbladder<br>* The Cxbladder Detect test, developed by Pacific Edge Ltd (O'Sullivan 2012; Holyoake 2008; National Health Committee 2015b) is a molecular diagnostic test, which consists of five mRNA transcripts measured in a small volume of urine.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants with bladder cancer who are correctly identified as having cancer (true positives) and no cancer (true negatives) by the Cxbladder test. | The Cxbladder test results will be compared to that of cystoscopy, which is the gold standard method for diagnosing urothelial cancer; the true positive and true negative rates will be measured, along with the false positive and false negative rates of the test. The results will be reported as sensitivity and specificity of the Cxbladder test for detecting urothelial cancer in patients with hematuria | The outcome measure will be assessed by 6 months after trial completion. | 
| Probability that patients identified as having cancer and no cancer by the Cxbladder test truly have cancer (positive predictive value; PPV), and truly have no cancer (negative predictive value; NPV) respectively. | The Cxbladder test results will be compared to that of cystoscopy, which is the gold standard method for diagnosing urothelial cancer; the true positive and true negative rates will be measured, along with the false positive and false negative rates of the test. The results will be reported as sensitivity and specificity of the Cxbladder test for detecting urothelial cancer in patients with recurrent disease. | Time Frame: The outcome measure will be assessed by 6 months after trial completion. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of the Cxbladder test's sensitivity, specificity, PPV and NPV with that of Cytology. | Performance characteristics (sensitivity, specificity, PPV and NPV) of the Cxbladder test for detecting recurring urothelial cancer will be compared to urine cytology, in addition to the gold standard test (cystoscopy). All comparator tests will be carried out on the same voided urine sample used for Cxbladder tests. | The outcome measure will be assessed by 6 months after trial completion. | 
| To compare the theoretical clinical outcome of patients tested using Cxbladder tests | To compare the theoretical clinical outcome of patients tested using Cxbladder tests in combination (Triage followed by Detect and / or Resolve) before investigative cystoscopy with evaluation by (positive, negative or suspicious) cystoscopy alone to establish the true proportion requiring cystoscopy, thereby determining the potential of Cxbladder to reduce or adjudicate the cystoscopy burden of hematuria patients and/or sub cohorts under clinical evaluation in a hospital urology clinic setting. | The outcome measure will be assessed by 6 months after trial completion. | 
| To compare the theoretical clinical outcome of patients tested using Cxbladder signatures before investigative cystoscopy with evaluation by cystoscopy alone to establish the true proportion requiring cystoscopy. | To compare the theoretical clinical outcome of patients tested using Cxbladder signatures before investigative cystoscopy with evaluation by (positive, negative or suspicious) cystoscopy alone to establish the true proportion requiring cystoscopy, thereby determining the potential of Cxbladder to reduce or adjudicate the cystoscopy burden of hematuria patients and/or sub cohorts under clinical evaluation in a hospital urology clinic setting. | The outcome measure will be assessed by 6 months after trial completion. | 
| Performance characteristics of Cxbladder Triage and Cxbladder Detect compared with results generated at other clinical sites | To evaluate the performance characteristics of Cxbladder Triage and Cxbladder Detect compared with results generated at other clinical sites, and to the results of the pulished clinical studies by O'Sullivan et al in 2012 and Kavalieris et al in 2015 | The outcome measure will be assessed by 6 months after trial completion. |