BladMetrix Urine Test for Monitoring Recurrence in Non-Muscle Invasive Bladder Cancer (BladMetrix)

National Multicenter Observational Study of Urine-Based BladMetrix Monitoring for Recurrence in Non-Muscle Invasive Bladder Cancer

This observational study evaluates the urine test BladMetrix for monitoring bladder cancer recurrences in people with non muscle invasive bladder cancer (NMIBC) who are in follow-up after surgery. The main goal is to evaluate the potential clinical utility of the BladMetrix test by comparing its performance with current follow-up methods, cystoscopy (looking into the bladder with a camera) and urine cytology (examining cells in the urine), using confirmed pathological histology as the reference standard for recurrence (return of disease).

Participants will be adults with NMIBC and a positive BladMetrix urine test at the time of their bladder tumor surgery (transurethral resection). After surgery, they will continue their usual follow-up at their local hospital according to national guidelines, including regular cystoscopies and urine cytology. At each planned follow-up visit over about 2 years, they will provide an extra urine sample for BladMetrix testing in addition to their routine examinations.

By comparing BladMetrix results with cystoscopy, urine cytology, and histology from any biopsies or tissue from surgery, we will estimate diagnostic accuracy measures such as sensitivity, specificity, negative predictive value, and positive predictive value for detecting bladder cancer recurrence. The goal is to see whether the BladMetrix urine test could safely replace parts of the cystoscopies, help clarify uncertain cystoscopy findings, and support more individualized follow-up schedules for people living with NMIBC.

Study Overview

• Status: Active, not recruiting
• Conditions: Urinary Bladder Neoplasms; Non-Muscle Invasive Bladder Neoplasms; Carcinoma, Transitional Cell, Bladder
• Intervention / Treatment: Diagnostic test: BladMetrix urine test

Detailed Description

Bladder cancer is a common malignancy and one of the most resource intensive cancers to manage because many patients live for years with a high risk of recurrence. Patients included in this study have non-muscle invasive bladder cancer (NMIBC), which is typically treated with transurethral resection of the bladder tumor (TURB) and, in selected cases, intravesical therapy. Despite adequate primary treatment, a large proportion of NMIBC patients experience one or more recurrences, and a subset progress to muscle-invasive disease. Current follow-up relies on frequent cystoscopy and urine cytology, which are invasive, burdensome for patients, and costly for the health care system.

BladMetrix is a molecular urine test based on a predefined panel of 8 DNA methylation biomarkers analyzed in DNA from urinary cells. Previous studies from our group have indicated that BladMetrix can detect bladder cancer with high sensitivity and specificity both for high and low grade cancers. In this national multicenter study, we aim to evaluate the potential clinical utility of BladMetrix in routine surveillance of NMIBC. The primary objective is to determine the diagnostic accuracy of BladMetrix for histologically confirmed bladder cancer recurrence, and to compare its performance with the current standard of care, namely cystoscopy and urine cytology, alone and in combination. Patients and user representatives have been actively involved in the planning of the study to help ensure that the research questions, follow-up procedures and information materials are clinically relevant and patient centered.

This is a prospective, observational cohort study conducted at multiple urology departments across all health regions in Norway. Adult patients with histologically verified NMIBC and a positive BladMetrix urine test at the time of TURB are eligible. After inclusion, all participants continue guideline based follow-up at their local hospital, including scheduled cystoscopies and urine cytology; the study does not alter clinical management. At each planned follow-up visit for approximately 2 years, urine is collected for BladMetrix analysis in parallel with routine examinations. Urinary cells are collected using a filtration-based device provided by CellCap Solutions ApS, where cells are captured on a filter that is subsequently transferred directly into a cassette containing lysis/storage buffer, facilitating standardized handling and preservation of cellular material for downstream molecular analysis. Cystoscopy findings, cytology results, and histopathological data from any biopsies or resections, together with relevant clinical variables, are recorded in a specially designed database (Medinsight). BladMetrix analyses are performed centrally, on coded samples, and the assay is scored positive/negative according to predefined thresholds. Personnel performing the BladMetrix analyses are blinded to all clinical data and pathological data, and test results are subsequently compared with the reference data.

The primary endpoint is the ability of BladMetrix to detect histologically confirmed bladder cancer recurrence, expressed by diagnostic accuracy measures including sensitivity, specificity, positive predictive value, and negative predictive value. Secondary endpoints include comparison of BladMetrix with urine cytology alone, with cystoscopy plus cytology, and with cystoscopy performed with adjunct imaging modalities when used in clinical practice. By evaluating this DNA methylation-based urine test in a large, real world multicenter NMIBC cohort, the study aims to determine whether BladMetrix could in the future contribute to reducing the number of cystoscopies, resolving equivocal cystoscopic findings, and enabling more individualized surveillance schedules without compromising patient safety.

The study was designed and initiated in close collaboration with head clinician Rolf Wahlqvist, MD, PhD Oslo University hospital - Aker, who has provided overall clinical leadership for the multicenter NMIBC follow up program. We also acknowledge all contributing urologists, including those holding clinical responsibility at each participating hospital (see Contacts and Locations), and the dedicated study nurses. Their combined work in patient recruitment, follow-up, data collection, and trial coordination is essential for the successful conduct of this study. Finally, the user representatives have contributed with their experience to strengthen the patient centered focus of the project.

• Study Type: Observational
• Enrollment (Estimated): 500

Contacts and Locations

Study Locations

• Norway
  • Bergen, Norway
    • Haukeland University Hospital
  • Lørenskog, Norway
    • Akershus University Hospital (Ahus)
  • Oslo, Norway
    • Oslo University Hospital - Aker
  • Tromsø, Norway
    • University Hospital of North Norway (UNN)
  • Trondheim, Norway
    • St. Olavs Hospital - Trondheim University Hospital
  • Tønsberg, Norway
    • Vestfold Hospital Trust (SiV)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Adults with non-muscle invasive bladder cancer (NMIBC) treated at participating urology departments in Norway form the study population. Participants are identified among patients undergoing transurethral resection of bladder tumor (TURB) for primary or recurrent NMIBC who have a positive BladMetrix urine test at baseline and are scheduled for guideline based outpatient surveillance at the participating hospitals. The population thus represents a real world NMIBC follow up cohort across all Norwegian health regions, including a spectrum of risk groups managed with standard cystoscopic surveillance, with or without intravesical therapy.

Description

Inclusion Criteria:

• Histologically verified non muscle invasive bladder cancer (NMIBC).
• Positive pre-TURB BladMetrix test.
• Planned outpatient follow-up at a participating hospital, with or without intravesical instillation therapy.
• Age ≥ 18 years.
• Able and willing to provide written informed consent and comply with study procedures, including repeated urine sampling.

Exclusion Criteria:

• NMIBC planned for radical treatment (for example, immediate cystectomy).
• Judged by the investigator as unlikely to be able to adhere to the follow_up schedule or provide required urine samples.
• Known cancer of the upper urinary tract at inclusion.
• Patients with permanent indwelling bladder catheter (for practical reasons in optimal urine sampling)

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
BladMetrix Positive NMIBC Cohort; Single cohort patients with a histologically confirmed NMIBC and a positive molecular urine marker test (BladMetrix) at the time of transurethral resection, prospectively followed at participating Norwegian hospitals with standard surveillance and parallel BladMetrix urine testing to assess recurrence	Diagnostic test: BladMetrix urine test; Molecular urine test (BladMetrix) based on a predefined panel of 8 DNA methylation biomarkers, performed at each routine follow-up visit to monitor for recurrence of non-muscle invasive bladder cancer; results are compared with cystoscopy, urine cytology, and histology but do not change standard clinical management within this study

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Diagnostic accuracy of BladMetrix versus white light cystoscopy for detecting histologically confirmed bladder cancer recurrence	Sensitivity, specificity, positive predictive value, and negative predictive value of the BladMetrix urine test for detection of bladder cancer recurrence, using histologically confirmed recurrence as the reference standard. The primary comparison is between BladMetrix and white light cystoscopy alone; additional comparisons with urine cytology will also be reported.	From first post TURB follow-up visit until end of urine sampling at 24 months after inclusion, with clinical follow-up for an additional 12 months to capture any recurrences occurring after the last urine sample

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Comparison of BladMetrix and urine cytology for recurrence detection	Sensitivity, specificity, positive predictive value, and negative predictive value of BladMetrix versus urine cytology alone for detecting histologically confirmed bladder cancer recurrence during follow_up.	From first post TURB follow-up visit until end of urine sampling at 24 months after inclusion, with clinical follow-up for an additional 12 months
Incremental value of BladMetrix in combination with cystoscopy and cytology	Diagnostic accuracy (sensitivity, specificity, positive predictive value, and negative predictive value) of BladMetrix combined with standard surveillance (cystoscopy with or without adjunct imaging and urine cytology) for detection of histologically confirmed bladder cancer recurrence, and assessment of whether BladMetrix detects recurrence earlier than standard methods.	From first post-TURB follow-up visit until end of urine sampling at 24 months after inclusion, with clinical follow-up for an additional 12 months

Collaborators and Investigators

• Sponsor: Oslo University Hospital
• Collaborators: The Research Council of Norway; Haukeland University Hospital; St. Olavs Hospital; University Hospital, Akershus; South-Eastern Norway Regional Health Authority; Oslo University Hospital - Aker; Vestfold Hospital Trust (SiV); University Hospital of North Norway (UNN); Clinical Therapy Research in the specialist health services; CellCap Solutions ApS - provides the filtration device used for urine sample collection and subsequent storage in this study
• Investigators: Study Chair: Rolf Wahlqvist, MD, PhD, Oslo University Hospital - Aker

Publications and helpful links

General Publications

• Vedeld HM, Pharo H, Sorbo AK, Brandt-Winge S, Five MB, Jeanmougin M, Guldberg P, Wahlqvist R, Lind GE. Distinct longitudinal patterns of urine tumor DNA in patients undergoing surveillance for bladder cancer. Mol Oncol. 2024 Nov;18(11):2684-2695. doi: 10.1002/1878-0261.13639. Epub 2024 May 8.
• Pharo HD, Jeanmougin M, Ager-Wick E, Vedeld HM, Sorbo AK, Dahl C, Larsen LK, Honne H, Brandt-Winge S, Five MB, Monteiro-Reis S, Henrique R, Jeronimo C, Steven K, Wahlqvist R, Guldberg P, Lind GE. BladMetrix: a novel urine DNA methylation test with high accuracy for detection of bladder cancer in hematuria patients. Clin Epigenetics. 2022 Sep 17;14(1):115. doi: 10.1186/s13148-022-01335-2.
• Andersson E, Dahmcke CM, Steven K, Larsen LK, Guldberg P. Filtration Device for On-Site Collection, Storage and Shipment of Cells from Urine and Its Application to DNA-Based Detection of Bladder Cancer. PLoS One. 2015 Jul 7;10(7):e0131889. doi: 10.1371/journal.pone.0131889. eCollection 2015.

Study record dates

Study Major Dates

• Study Start (Actual): October 3, 2019
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2027

Study Registration Dates

• First Submitted: March 30, 2026
• First Submitted That Met QC Criteria: March 30, 2026
• First Posted (Actual): April 6, 2026

Study Record Updates

• Last Update Posted (Actual): April 9, 2026
• Last Update Submitted That Met QC Criteria: April 5, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Bladder cancer; Cystoscopy; Follow-up; Surveillance; Diagnostic accuracy; Sensitivity; Specificity; Recurrence monitoring; Urine biomarker; Non-muscle invasive bladder cancer (NMIBC); BladMetrix; Urine DNA methylation; Molecular urine test; Monitoring of bladder cancer; Urine cytology
• Additional Relevant MeSH Terms: Urogenital Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Male Urogenital Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Urologic Neoplasms; Urinary Bladder Diseases; Non-Muscle Invasive Bladder Neoplasms; Carcinoma; Hypersensitivity; Urinary Bladder Neoplasms
• Other Study ID Numbers: 28461

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual participant data will not be shared. The Regional Ethics Committee (REC) approval and the informed consent form limit use of participants' data to the purposes described in this study and do not include provision for external sharing of coded participant-level data outside the participating hospitals, in accordance with Norwegian and EU data protection regulations.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No