Replacing Invasive Cystoscopy With Urine Testing for Non-muscle Invasive Bladder Cancer Surveillance

Study Overview
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Brief Summary
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The purpose of this research is to determine whether bladder cancer monitoring can be improved by replacing some cystoscopy procedures with urine testing. Specifically, this study examines whether there are any differences in urinary symptoms, discomfort, number of invasive procedures, anxiety, complications, cancer recurrence or cancer progression when some cystoscopy procedures are replaced with urine testing.

Detailed Description
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This is a multi-site randomized phase 2 trial including 240 patients with early-stage bladder cancer, in which patients will be randomized 1:1:1 to programmatic surveillance with the Xpert bladder cancer urine test, the Bladder EpiCheck urine test, or frequent cystoscopy. The primary outcome will be urinary quality of life measured 1 to 3 days after surveillance. This study will have three groups, also called arms: (1) Frequent Cystoscopy Arm, (2) Xpert Urine Test Arm, and (3) Epicheck Urine Test Arm. The aim of Frequent Cystoscopy is to detect any cancer that might have come back within the bladder by frequently inspecting the bladder. Those in the cystoscopy arm will have a cystoscopy procedure at specified time points for two years. The goal of the Xpert Urine Test arm is to detect any cancer that might have come back within the bladder, while decreasing the number of invasive cystoscopy procedures. Those in the Xpert arm will have a Xpert urine test and a check-up with a medical doctor at 6 months and 18 months, and have a cystoscopy procedure at 12 months and 24 months. The aim of the EpiCheck Urine Test arm is to detect any cancer that might have come back within the bladder, while decreasing the number of invasive cystoscopy procedures. Those in the EpiCheck Urine Test arm will have an Epicheck urine test and a check-up with a medical doctor at 6 months and 18 months and will have a cystoscopy procedure at 12 months and 24 months. The study performance period is 24 months.

Official Title
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Replacing Invasive Cystoscopy With Urine Testing for Non-muscle Invasive Bladder Cancer Surveillance

Conditions
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Non-muscle-invasive Bladder Cancer

Intervention / Treatment
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* Procedure: Cystoscopy
* Diagnostic Test: Bladder EpiCheck urine test
* Diagnostic Test: Xpert Bladder Cancer Monitor urine test


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged 18 years or older History of low grade intermediate-risk non-muscle invasive bladder cancer, defined as most recent pathology report showing any of the following: multifocal low grade non-invasive urothelial carcinoma of any size solitary low grade non-invasive urothelial carcinoma greater than 3cm in size recurrent low grade non-invasive urothelial carcinoma, with recurrence within 1 year of previous tumor resection Stated willingness to comply with all study procedures and availability for the duration of the study No evidence for recurrence at cystoscopy ≤4 months after most recent tumor resection Ability to consent in English or Spanish Exclusion Criteria: History of total cystectomy of the bladder. History of urinary diversion (e.g., neo-bladder, colon pouch, or ileal conduit). History of muscle-invasive bladder tumor. Pregnancy or lactation. History of urothelial carcinoma of the ureter or renal pelvis status post endoscopic treatment or with evidence of recurrent upper tract disease (inclusion allowed if status post nephroureterectomy and recurrence free at time of inclusion) Anatomic constraints making cystoscopy impossible (e.g., history of urethrectomy, obliterated urethra secondary to stricture). Inability to provide a voided urine sample.

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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Design Details

Primary Purpose: Health Services Research
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Health care delivery parallel trial with 1:1:1 randomization
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Frequent Cystoscopy<br>Cystoscopy is conducted at 6, 12, 18, and 24 months for patients undergoing surveillance for low grade intermediate-risk non-muscle invasive bladder cancer | Procedure: Cystoscopy<br>* Cystoscopy entails direct inspection of the bladder via a cystoscope that is inserted into a patient's urethra.<br>|
| Experimental: Xpert Urine Test<br>Xpert arm includes urine testing using the Xpert Bladder Cancer Monitor urine test at 6 and 18 months. Cystoscopy is conducted at 12 and 24 months for patients undergoing surveillance for low grade intermediate-risk non-muscle invasive bladder cancer | Procedure: Cystoscopy<br>* Cystoscopy entails direct inspection of the bladder via a cystoscope that is inserted into a patient's urethra.<br>Diagnostic Test: Xpert Bladder Cancer Monitor urine test<br>* A 4.5 ml sample of voided urine is added to Xpert® Urine Transport Reagent, mixed, and then 4ml of treated urine are transferred to the Sample Chamber of the cartridge. In the cartridge, cells in the urine sample are captured on a filter and lysed by sonication. The released nucleic acid is eluted, mixed with dry RT-PCR reagents, and the solution is transferred to the reaction tube for RT-PCR and detection.<br>|
| Experimental: EpiCheck Urine Text<br>EpiCheck arm includes urine testing using the Bladder EpiCheck urine test at 6 and 18 months. Cystoscopy is conducted at 12 and 24 months for patients undergoing surveillance for low grade intermediate-risk non-muscle invasive bladder cancer. | Procedure: Cystoscopy<br>* Cystoscopy entails direct inspection of the bladder via a cystoscope that is inserted into a patient's urethra.<br>Diagnostic Test: Bladder EpiCheck urine test<br>* The Bladder EpiCheck is a laboratory-developed test for early-stage non-muscle invasive bladder cancer. The Bladder EpiCheck test is a DNA methylation test that is run on DNA extracted from cell pellet from centrifuged urine according to Standardized Operating Procedures. The test has internal controls and a dedicated software to ensure required quality assurance processes and prompt reporting of results.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quality of Life Questionnaire-Non-Muscle Invasive Bladder Cancer 24 (EORTC QLQ-NMIBC24) | Measuring change from baseline. Score range: 0-100. Lower score indicates higher quality of life. | Assessed at 3, 6, 12, 18, and 24 months. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bladder, Cancer, Urology, Cystoscopy, Xpert, EpiCheck, Urine test