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

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.

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)