Urine Testing vs Cystoscopy for Bladder Cancer Surveillance

(ReplaceCysto Trial)

Recruiting in Palo Alto (17 mi)

+5 other locations

Overseen by Florian R Schroeck, MD, MS

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: White River Junction Veterans Affairs Medical Center

Disqualifiers: Total cystectomy, Urinary diversion, Muscle-invasive tumor, Pregnancy, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the treatment Bladder EpiCheck urine test and Xpert Bladder Cancer Monitor for bladder cancer surveillance?

The Xpert Bladder Cancer Monitor is a urine test that checks for specific mRNA markers linked to bladder cancer, and studies show it is effective in monitoring non-muscle invasive bladder cancer. The Bladder EpiCheck urine test has a high specificity of 88% and a negative predictive value of 99.3% for high-grade bladder cancer, suggesting it can effectively reduce the need for invasive follow-up procedures like cystoscopy. ^{1 2 3 4 5}

Is the Xpert Bladder Cancer Monitor or Bladder EpiCheck urine test safe for humans?

The research does not specifically mention safety concerns for the Xpert Bladder Cancer Monitor or Bladder EpiCheck urine tests, suggesting they are generally considered safe for use in humans. ^{1 2 5 6 7}

How does urine testing differ from cystoscopy for bladder cancer surveillance?

Urine testing, like the Xpert Bladder Cancer Monitor, is a non-invasive method that uses a urine sample to detect specific mRNA markers associated with bladder cancer, potentially reducing the need for cystoscopy, which is an invasive procedure involving a camera inserted into the bladder. ^{1 2 6 8 9}

Research Team

Florian R Schroeck, MD, MS

Principal Investigator

White River Junction VA Healthcare System

Eligibility Criteria

This trial is for adults over 18 who can consent in English or Spanish, have a history of low-grade intermediate-risk non-muscle invasive bladder cancer, and are willing to follow the study's procedures. Pregnant women, those with total bladder removal or urinary diversions, muscle-invasive tumors, upper tract disease unless surgically treated and recurrence-free, or anatomic issues preventing cystoscopy cannot join.

Inclusion Criteria

I am willing and able to follow the study's procedures and be available for its duration.

My latest bladder exam showed no signs of cancer returning.

I am 18 years old or older.

Exclusion Criteria

I had bladder cancer in the ureter or kidney area but have been treated.

I cannot undergo cystoscopy due to issues with my urethra.

I cannot provide a urine sample on my own.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are assigned to one of three arms: Frequent Cystoscopy, Xpert Urine Test, or EpiCheck Urine Test, with procedures conducted over 24 months

24 months

Visits at 6, 12, 18, and 24 months

Follow-up

Participants are monitored for urinary quality of life and cancer recurrence or progression

4 weeks

Treatment Details

Interventions

• Bladder EpiCheck urine test (Diagnostic Test)
• Xpert Bladder Cancer Monitor urine test (Diagnostic Test)

Trial Overview The study aims to see if urine tests (Xpert Bladder Cancer Monitor and Bladder EpiCheck) can replace some cystoscopy procedures for monitoring bladder cancer. It will assess changes in urinary symptoms, discomfort levels, anxiety, complications as well as rates of cancer detection and progression.

Participant Groups

Group I: Xpert Urine Test Experimental Treatment 2 Interventions

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

Group II: EpiCheck Urine Text Experimental Treatment 2 Interventions

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.

Group III: Frequent Cystoscopy Active Control 1 Intervention

Cystoscopy is conducted at 6, 12, 18, and 24 months for patients undergoing surveillance for low grade intermediate-risk non-muscle invasive bladder cancer

Who Is Running the Clinical Trial?

White River Junction Veterans Affairs Medical Center

Lead Sponsor

Trials

32

Recruited

17,900+

Medical University of South Carolina

Collaborator

Trials

994

Recruited

7,408,000+

Dr. Erik Summers

Medical University of South Carolina

Chief Medical Officer

MD from University of Alabama at Birmingham

Dr. Patrick J. Cawley

Medical University of South Carolina

Chief Executive Officer

MD, MBA

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Dr. Douglas R. Lowy

National Cancer Institute (NCI)

Chief Executive Officer since 2023

MD from New York University School of Medicine

Dr. Monica Bertagnolli

National Cancer Institute (NCI)

Chief Medical Officer since 2022

MD from Harvard Medical School

University of Texas Southwestern Medical Center

Collaborator

Trials

1,102

Recruited

1,077,000+

Daniel K. Podolsky

University of Texas Southwestern Medical Center

Chief Executive Officer since 2008

MD from Harvard Medical School

Robert L. Bass

University of Texas Southwestern Medical Center

Chief Medical Officer since 2019

MD from University of Texas Southwestern Medical School

Findings from Research

In a study of 230 patients with non-muscle invasive bladder cancer (NMIBC), the Xpert BC Monitor test demonstrated a significantly higher sensitivity (46.2%) for detecting recurrences compared to traditional urine cytology (11.5%).

The Xpert BC Monitor showed particularly strong performance in detecting high-grade tumors, with a sensitivity of 85.7%, while maintaining good specificity (77%), although it did not match the specificity of cytology (97.2%).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diagnostic predictive value of Xpert Bladder Cancer Monitor in the follow-up of patients affected by non-muscle invasive bladder cancer. D Elia, C., Pycha, A., Folchini, DM., et al.[2019]

The Xpert Bladder Cancer Monitor Test (XBC) demonstrated significantly higher sensitivity (76.9%) and negative predictive value (93.0%) compared to voided urinary cytology (VUC), which had a sensitivity of only 38.4% and a negative predictive value of 83.3% for detecting malignant bladder tumors.

The study suggests that the XBC could potentially allow for longer intervals between recommended follow-up cystoscopies, as it outperformed VUC in predicting both malignant histopathological results and suspicious cystoscopic findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The performance of the Xpert Bladder Cancer Monitor Test and voided urinary cytology in the follow-up of urinary bladder tumors. Smrkolj, T., Cegovnik Primozic, U., Fabjan, T., et al.[2021]

The Xpert® Bladder Cancer Monitor test demonstrated a significantly higher sensitivity (52.4%) for detecting bladder cancer compared to urinary cytology (17.9%) in a study involving 416 patients, suggesting it is a more effective tool for monitoring non-muscle invasive bladder cancer (NMIBC).

While the specificity of the Xpert® Bladder Cancer Monitor (78.4%) was lower than that of cytology (98.5%), its use alongside cytology could potentially reduce the need for cystoscopies, minimizing patient discomfort and healthcare costs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diagnostic value of Xpert® Bladder Cancer Monitor in the follow-up of patients affected by non-muscle invasive bladder cancer: an update. D'Elia, C., Folchini, DM., Mian, C., et al.[2022]

The Bladder EpiCheck (BE) urine test can significantly reduce healthcare costs for follow-up in non-muscle invasive bladder cancer (NMIBC) patients, with estimated savings of approximately 1.6 million euros annually in the Netherlands.

While using the BE test may lead to a slight delay in detecting recurrences—averaging 3.9 months for low-risk and 1.3 months for high-risk patients—it maintains a high negative predictive value of 99.3% for high-grade NMIBC, making it a reliable option for reducing the need for cystoscopies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bladder EpiCheck urine test in the follow-up of NMIBC: a cost analysis. Hekman, MCH., Wijn, SRW., Lotan, Y., et al.[2023]

The Xpert® Bladder Cancer Monitor assay can help reduce unnecessary cystoscopies and urine cytology tests in patients under active surveillance for Non-muscle Invasive Bladder Cancer, with a potential avoidance of 73.9% of these procedures for patients with two consecutive negative tests.

In a study of 139 patients with a median follow-up of 23 months, those with multiple negative Xpert tests had a high failure-free survival rate, indicating that the assay is effective in monitoring patients without increasing the risk of missing cancer recurrence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Xpert Bladder Cancer Monitor May Avoid Cystoscopies in Patients Under "Active Surveillance" for Recurrent Bladder Cancer (BIAS Project): Longitudinal Cohort Study. Fasulo, V., Paciotti, M., Lazzeri, M., et al.[2022]

The Bladder EpiCheck (BE) urine assay demonstrated a high negative predictive value (NPV) of 95.1% for detecting non-muscle-invasive bladder cancer (NMIBC) recurrence, increasing to 99.3% when excluding low-grade tumors, based on a study of 353 eligible patients.

With a specificity of 88.0% and a sensitivity of 91.7% for high-grade tumors, the BE test could significantly reduce the need for invasive follow-up procedures like cystoscopy, making it a promising alternative in NMIBC management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Performance of the Bladder EpiCheck™ Methylation Test for Patients Under Surveillance for Non-muscle-invasive Bladder Cancer: Results of a Multicenter, Prospective, Blinded Clinical Trial. Witjes, JA., Morote, J., Cornel, EB., et al.[2019]

Bladder EpiCheck™, a non-invasive urine test for non-muscle-invasive bladder cancer (NMIBC), demonstrated a high specificity of 88% and a negative predictive value (NPV) of 94.4% for detecting any cancer, and 99.3% for high-grade cancer, based on analysis of 357 patients.

The test significantly improved the predictive ability for cancer recurrence when added to standard clinical variables, reducing unnecessary investigations and enhancing decision-making in patient surveillance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diagnostic accuracy, clinical utility and influence on decision-making of a methylation urine biomarker test in the surveillance of non-muscle-invasive bladder cancer. D'Andrea, D., Soria, F., Zehetmayer, S., et al.[2020]

The Bladder EpiCheck test, when used alongside cytology, can effectively identify high-grade urothelial carcinoma in patients with atypical cells or those suspicious for high-grade carcinoma, potentially reducing the need for cystoscopies in these cases.

In patients with a cytological diagnosis of negative for high-grade urothelial carcinoma, the Bladder EpiCheck test does not provide additional benefit, suggesting that cytology alone is a safe and cost-effective approach for monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The combination cytology/epichek test in non muscle invasive bladder carcinoma follow-up: Effective tool or useless expence? Pierconti, F., Martini, M., Fiorentino, V., et al.[2021]

References

1. England pubmed.ncbi.nlm.nih.gov

Diagnostic predictive value of Xpert Bladder Cancer Monitor in the follow-up of patients affected by non-muscle invasive bladder cancer. [2019]

2. Poland pubmed.ncbi.nlm.nih.gov

The performance of the Xpert Bladder Cancer Monitor Test and voided urinary cytology in the follow-up of urinary bladder tumors. [2021]

3. England pubmed.ncbi.nlm.nih.gov

Diagnostic value of Xpert® Bladder Cancer Monitor in the follow-up of patients affected by non-muscle invasive bladder cancer: an update. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Xpert bladder cancer monitor in surveillance of bladder cancer: Systematic review and meta-analysis. [2022]

5. Germany pubmed.ncbi.nlm.nih.gov

Bladder EpiCheck urine test in the follow-up of NMIBC: a cost analysis. [2023]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Xpert Bladder Cancer Monitor May Avoid Cystoscopies in Patients Under "Active Surveillance" for Recurrent Bladder Cancer (BIAS Project): Longitudinal Cohort Study. [2022]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Performance of the Bladder EpiCheck™ Methylation Test for Patients Under Surveillance for Non-muscle-invasive Bladder Cancer: Results of a Multicenter, Prospective, Blinded Clinical Trial. [2019]

8. England pubmed.ncbi.nlm.nih.gov

Diagnostic accuracy, clinical utility and influence on decision-making of a methylation urine biomarker test in the surveillance of non-muscle-invasive bladder cancer. [2020]

9. United States pubmed.ncbi.nlm.nih.gov

The combination cytology/epichek test in non muscle invasive bladder carcinoma follow-up: Effective tool or useless expence? [2021]