Urine Testing vs Cystoscopy for Bladder Cancer Surveillance

(ReplaceCysto Trial)

Recruiting at 9 trial locations

Overseen By Laura Jensen, MPH

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: White River Junction Veterans Affairs Medical Center

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

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 6

Duration: 24 months

240 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if urine tests can replace some cystoscopy procedures for monitoring bladder cancer. It examines whether urine tests affect symptoms, discomfort, the number of invasive procedures, anxiety, complications, and cancer progression differently than regular cystoscopies. Participants are divided into groups receiving either urine tests (such as the Bladder EpiCheck urine test or the Xpert Bladder Cancer Monitor urine test) or more frequent cystoscopies. This trial suits individuals with a history of low-grade bladder cancer who have not experienced a recurrence in recent months. As an unphased trial, it offers the opportunity to contribute to innovative research that could enhance future bladder cancer monitoring methods.

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 prior data suggests that these urine tests are safe for bladder cancer surveillance?

A previous study demonstrated that the Bladder EpiCheck urine test accurately identified individuals with and without bladder cancer, suggesting its reliability and safety for patients.

Research on the Xpert Bladder Cancer Monitor urine test shows it correctly identifies bladder cancer in 69% to 87% of cases and correctly rules it out in about 75% to 76% of cases. This indicates its effectiveness in detecting the return of bladder cancer.

Both tests are non-invasive, avoiding surgery or instruments entering the body. This generally makes them easier to tolerate and results in fewer side effects compared to procedures like cystoscopy. Studies have not reported any major safety concerns with these tests. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about these methods because they offer a less invasive approach to monitoring bladder cancer. While the standard of care typically involves frequent cystoscopies, which can be uncomfortable and invasive, the Bladder EpiCheck and Xpert Bladder Cancer Monitor tests provide a non-invasive alternative through urine testing. These urine tests are designed to be used at intervals of 6 and 18 months, potentially reducing the need for as many cystoscopies to once every 12 and 24 months. This could improve patient comfort and compliance with bladder cancer surveillance while still effectively monitoring for cancer recurrence.

What evidence suggests that this trial's urine tests could be effective for bladder cancer surveillance?

This trial will compare the effectiveness of different surveillance methods for bladder cancer. Participants in the EpiCheck arm will undergo urine testing with the Bladder EpiCheck urine test at 6 and 18 months, and cystoscopy at 12 and 24 months. Research has shown that the Bladder EpiCheck urine test effectively detects bladder cancer recurrences, with a high accuracy rate of 99% for ruling out high-grade cancer when the test result is negative. Additionally, studies indicate it correctly identifies cancer 90% of the time and accurately rules out cancer 83% of the time in patients being monitored, making it a strong tool for ongoing checks.

Participants in the Xpert arm will use the Xpert Bladder Cancer Monitor urine test at 6 and 18 months, with cystoscopy at 12 and 24 months. The Xpert Bladder Cancer Monitor also shows promise, detecting cancer recurrences with an accuracy of 83-87% and ruling out cancer 75-76% of the time. This test is especially effective at finding high-grade cancer, making it useful for regular follow-up checks. Both tests are non-invasive and provide reliable results. ^{3 6 7 8 9}

Who Is on the Research Team?

Florian R Schroeck, MD, MS

Principal Investigator

White River Junction VA Healthcare System

Are You a Good Fit for This Trial?

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 can give my consent in English or Spanish.

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Bladder EpiCheck urine test
• Xpert Bladder Cancer Monitor urine 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.

How Is the Trial Designed?

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+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

University of Texas Southwestern Medical Center

Collaborator

Trials

1,102

Recruited

1,077,000+

Published Research Related to This Trial

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 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]

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]

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 (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 shows a pooled sensitivity of 73% and specificity of 77% for detecting recurrences in patients with non-muscle invasive bladder cancer (NMIBC), based on a systematic review of 11 studies involving 2,896 patients.

For high-grade recurrences, the sensitivity increases to 86%, indicating that the Xpert BC monitor is particularly effective in identifying more aggressive forms of the disease, while sensitivity drops to 58% for low-grade recurrences.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Xpert bladder cancer monitor in surveillance of bladder cancer: Systematic review and meta-analysis. Sharma, G., Sharma, A., Krishna, M., et al.[2022]

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 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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11864238/

North American study and meta-analysis evaluating ... Bladder EpiCheck (BE) is a novel methylation-based PCR urine test for the detection of non-muscle invasive bladder cancer (NMIBC) recurrences.

2. nucleix.com nucleix.com/bladder-epicheck-5/

Bladder EpiCheck Bladder EpiCheck demonstrated high Negative Predictive Value (NPV) of 99% for high-grade cancer, meaning that when receiving a negative Bladder EpiCheck result, ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.e16597

Clinical performance of Bladder EpiCheck methylation test ... The Bladder EpiCheck test has a better sensitivity than urine cytology and may be utilized as a part of the active surveillance strategy for NIMBC recurrence.

4. sciencedirect.com sciencedirect.com/science/article/pii/S2588931118300968

Performance of the Bladder EpiCheck™ Methylation Test ... The validation study [7] showed 90% sensitivity, 83% specificity, and NPV of 97% among 222 NMIBC patients undergoing surveillance.

5. urotoday.com urotoday.com/recent-abstracts/urologic-oncology/bladder-cancer/153412-use-of-bladder-epicheck-in-the-follow-up-of-high-risk-non-muscle-invasive-bladder-cancer-a-systematic-literature-review-beyond-the-abstract.html

Use of Bladder Epicheck® in the Follow-up of High-Risk ... The mean Se for recurrence detection was 88% for HG and 45% for LG. The weighted mean Se, specificity (Sp), positive predictive value (PPV), and ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10420163/

Bladder Epicheck Test: A Novel Tool to Support Urothelial ... For Bladder EpiCheck, the sensitivity and specificity of bladder cancer recurrence detection were very high, with values similar to those ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S266616832400329X

Replacing Invasive Cystoscopy with Urine Testing for Non– ... Preliminary data show that the Xpert Bladder Cancer Monitor test (mRNA based) and Bladder EpiCheck (DNA methylation test) may replace cystoscopy procedures, ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT06020807

Analytical Specificity of Bladder EpiCheck Test in Healthy ... This is a prospective study to establish the analytical specificity of Bladder EpiCheck test in urine samples from healthy population and urology patients ...

9. prevention.cancer.gov prevention.cancer.gov/funding-and-grants/funded-grants/R37CA275916

Funded Grants | Division of Cancer Prevention If bladder cancer urine tests significantly decrease the burden of surveillance, our data will provide a strong justification for a subsequent comparative ...