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RecruitingNCT05796375ReplaceCystoUpdated Sep 16, 2026

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

A Phase 2 interventional study of Cystoscopy and Bladder EpiCheck urine test in Non-muscle-invasive Bladder Cancer, sponsored by White River Junction Veterans Affairs Medical Center. Recruiting at 10 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-09-16.

Sponsored by White River Junction Veterans Affairs Medical Center · Phase 2, Interventional, and Health services research

Phase
Phase 2
Study type
Interventional
Enrollment
240
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study summary

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.

Read the detailed description

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.

02

Conditions studied

  • Non-muscle-invasive Bladder Cancer

Keywords

  • Bladder
  • Cancer
  • Urology
  • Cystoscopy
  • Xpert
  • EpiCheck
  • Urine test
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  1. Aged 18 years or older
  2. 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
  3. Stated willingness to comply with all study procedures and availability for the duration of the study
  4. No evidence for recurrence at cystoscopy ≤6 months after most recent tumor resection
  5. Ability to consent in English or Spanish

Exclusion criteria

Exclusion Criteria:

  1. History of total cystectomy of the bladder.
  2. History of urinary diversion (e.g., neo-bladder, colon pouch, or ileal conduit).
  3. History of muscle-invasive bladder tumor.
  4. Pregnancy or lactation.
  5. 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)
  6. Anatomic constraints making cystoscopy impossible (e.g., history of urethrectomy, obliterated urethra secondary to stricture).
  7. Inability to provide a voided urine sample.
04

Study design

Phase
Phase 2
Primary purpose
Health services research
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
240 participants (estimated)

Study arms

  • Active comparator
    Frequent Cystoscopy

    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

  • Experimental
    Xpert Urine Test

    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 · Diagnostic Test: Xpert Bladder Cancer Monitor urine test

  • Experimental
    EpiCheck Urine Text

    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 · Diagnostic Test: Bladder EpiCheck urine test

Interventions

  • ProcedureCystoscopy

    Cystoscopy entails direct inspection of the bladder via a cystoscope that is inserted into a patient's urethra.

  • Diagnostic testBladder EpiCheck urine test

    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.

  • Diagnostic testXpert Bladder Cancer Monitor urine test

    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.

05

What researchers measure

Primary outcomes

  1. 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.

    Time frame: Assessed at 3, 6, 12, 18, and 24 months.

06

Study locations

8 of 10 sites recruiting
  • West Haven VA Medical Center
    West Haven, Connecticut 06516, United States
    • Alicia Roy · Contact · Alicia.Roy@va.gov · 203-932-5711
    • Preston Sprenkle, MD · Principal investigator
    Recruiting
  • Bay Pines VA Healthcare System
    Bay Pines, Florida 33744, United States
    Recruiting
  • James A. Haley Veterans' Hospital
    Tampa, Florida 33612, United States
    Withdrawn
  • VA Boston Jamaica Plains Campus
    West Roxbury, Massachusetts 02132, United States
    • Laura MacAdam, NP · Contact · Laura.MacAdam@va.gov · 857-407-8074
    • Lori Lerner, MD · Sub investigator
    • Jeffrey Ellis, MD · Principal investigator
    Recruiting
  • VA St.Louis Healthcare System
    St Louis, Missouri 63016, United States
    • Carley Browning · Contact · Carley.Browning@va.gov · 314-652-4100
    • Lewis Thomas, MD · Principal investigator
    Recruiting
  • Dartmouth Hitchcock Medical Center
    Lebanon, New Hampshire 03756, United States
    Recruiting
  • University Hospitals Cleveland Medical Center
    Cleveland, Ohio 44106, United States
    Recruiting
  • Medical University of South Carolina
    Charleston, South Carolina 29425, United States
    Active, not recruiting
  • UT Southwestern Medical Center
    Dallas, Texas 75235, United States
    Recruiting
  • White River Junction Veterans Healthcare System
    White River Junction, Vermont 05009, United States
    Recruiting
07

References and documents

Publications

  • Koo K, Zubkoff L, Sirovich BE, Goodney PP, Robertson DJ, Seigne JD, Schroeck FR. The Burden of Cystoscopic Bladder Cancer Surveillance: Anxiety, Discomfort, and Patient Preferences for Decision Making. Urology. 2017 Oct;108:122-128. doi: 10.1016/j.urology.2017.07.016. Epub 2017 Jul 21. PubMed 28739405 ↗
  • Schroeck FR, Lynch KE, Li Z, MacKenzie TA, Han DS, Seigne JD, Robertson DJ, Sirovich B, Goodney PP. The impact of frequent cystoscopy on surgical care and cancer outcomes among patients with low-risk, non-muscle-invasive bladder cancer. Cancer. 2019 Sep 15;125(18):3147-3154. doi: 10.1002/cncr.32185. Epub 2019 May 23. PubMed 31120559 ↗
  • Schroeck FR, Grubb R, MacKenzie TA, Ould Ismail AA, Jensen L, Tsongalis GJ, Lotan Y. Clinical Trial Protocol for "Replace Cysto": Replacing Invasive Cystoscopy with Urine Testing for Non-muscle-invasive Bladder Cancer Surveillance-A Multicenter, Randomized, Phase 2 Healthcare Delivery Trial Comparing Quality of Life During Cancer Surveillance with Xpert Bladder Cancer Monitor or Bladder EpiCheck Urine Testing Versus Frequent Cystoscopy. Eur Urol Open Sci. 2024 Mar 21;63:19-30. doi: 10.1016/j.euros.2024.02.018. eCollection 2024 May. PubMed 38558761 ↗

Individual participant data

Plan to share: No

08

Registry details

Key details

Study ID
NCT05796375
Lead sponsor
White River Junction Veterans Affairs Medical Center
Collaborators
National Cancer Institute (NCI), University of Texas Southwestern Medical Center, Medical University of South Carolina
Responsible party
Florian Schroeck (Chief, Section of Urology, White River Junction Veterans Affairs Medical Center) — Principal investigator
First posted
Apr 3, 2023
Start date
Nov 17, 2023
Primary completion
Nov 30, 2028 (estimated)
Completion
Dec 30, 2028 (estimated)
Last update
Sep 16, 2026

Study contacts

Prabhavathi Loganathan, MS
Contact
Prabhavath.Loganathan@va.gov
802-295-9363 ext. 6914
Laura Jensen, MPH
Contact
Laura.Jensen@va.gov
802-280-5298
Florian R Schroeck, MD, MS
principal investigator · White River Junction VA Healthcare System

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
Yes
View the source record on ClinicalTrials.gov ↗

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