Prospective Validation Study of High Volume Urine DNA Testing in Individuals With Suspicion of Urothelial Cancer (UROSCOUT-1)

Observational Prospective Multicenter Validation Study Investigating the Possibility of Replacing Cystoscopies With High Volume Urine DNA Testing in Individuals With Suspicion of Urothelial Cancer (UROSCOUT-1)

Urothelial cancers of the bladder and upper urinary tract account for over 200,000 deaths and 600,000 diagnoses annually worldwide. The most common presenting symptom is hematuria (blood in urine), triggering a cascade of tests, including an invasive examination of the bladder using a flexible scope (cystoscopy). Millions of cystoscopies are performed every year worldwide for patients presenting with hematuria, but only 10% result in a cancer diagnosis. The UROSCOUT-1 trial is a prospective multicenter observational study that explores the potential of urine tumor DNA (utDNA) testing to replace a significant portion of cystoscopies in the diagnostic setting for hematuria or other reasons to rule out urothelial cancer. The goal is to enhance patient quality of life, reduce healthcare costs, and address increased workloads in urology centers. Sample collection will be conducted by mail, and the samples will be analyzed in a blinded manner, without knowledge of which patients are diagnosed with cancer. Random subsampling will be applied to cancer-negative patients to achieve an approximate 1:1 ratio between cancer-positive and -negative patients.

Study Overview

• Status: Recruiting
• Conditions: Urothelial Carcinoma

• Study Type: Observational
• Enrollment (Estimated): 3000

Contacts and Locations

• Study Contact: Name: Jussi Nikkola, MD PhD; Phone Number: +358 03311611; Email: jussi.nikkola@fimnet.fi

Study Locations

• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada
      • Recruiting
      • Vancouver Prostate Centre
      • Principal Investigator: Peter Black
      • Contact: Peter Black
• Finland
  • Helsinki, Finland
    • Recruiting
    • Helsinki University Hospital
    • Contact: Riikka Järvinen
    • Contact: Tuomas Jalanko
  • Pori, Finland
    • Recruiting
    • Satasairaala Hospital
    • Contact: Marjo Seppänen
  • Seinäjoki, Finland
    • Recruiting
    • Seinäjoki Central Hospital
    • Contact: Henry Haapiainen
  • Tampere, Finland
    • Recruiting
    • Tampere University Hospital and Tampere University
    • Contact: Jussi Nikkola
    • Principal Investigator: Jussi Nikkola
    • Principal Investigator: Matti Annala
    • Contact: Thea Veitonmäki
  • Turku, Finland
    • Recruiting
    • Turku University Hospital
    • Contact: Peter Boström
    • Contact: Pertti Nurminen
• Japan
  • Osaka, Japan
    • Recruiting
    • Kindai University Hospital
    • Contact: Kazutoshi Fujita
• United States
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Not yet recruiting
      • Jesse Brown Department Of Veterans Affairs Medical Center
      • Contact: Joel Cornfield

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Probability Sample

Study Population

Patients scheduled for diagnostic cystoscopy to rule out urothelial cancer due to hematuria, imaging, or urine cytology findings.

Description

Inclusion Criteria:

• Willing and able to provide informed consent
• Patient has been scheduled for cystoscopy to rule out urothelial cancer

Exclusion Criteria:

• Prior diagnosis of urothelial cancer (i.e. bladder cancer or upper tract urothelial carcinoma)

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sensitivity and specificity of urine tumor DNA (utDNA) test for urothelial cancer detection	Sensitivity and specificity of utDNA test for urothelial cancer detection, using histologically confirmed cancer diagnoses within 1 year of the diagnostic workup as ground truth	1 year after diagnostic workup

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sensitivity and specificity of cystoscopy for urothelial cancer detection	Sensitivity and specificity of cystoscopy for urothelial cancer detection, using histologically confirmed cancer diagnoses within 1 year of the diagnostic workup as ground truth	1 year after diagnostic workup
Sensitivity and specificity of urine cytology for urothelial cancer detection	Sensitivity and specificity or urine cytology for urothelial cancer detection, using histologically confirmed cancer diagnoses within 1 year of the diagnostic workup as ground truth	1 year after diagnostic workup
Time to diagnosis of urothelial cancer in patients with a positive utDNA test but negative cystoscopy	Time to diagnosis of urothelial cancer in patients with a positive utDNA test but negative cystoscopy	2, 5, and 10 years after diagnostic utDNA testing
Adverse event rate for cystoscopy	Adverse event rate for cystoscopy, based on CTCAE 5.0	4 weeks after cystoscopy
Technical success rate of utDNA test	Fraction of all analyzed urine samples for which the analysis met the quality control criteria for a technically successful analysis	Immediately after utDNA sample analysis
Estimate of diagnostic cystoscopies avoided	Estimated fraction of diagnostic cystoscopies that could have been avoided by pre-screening patients with a utDNA test (calculated as the fraction of all diagnostic utDNA samples that were negative and for which subsequent cystoscopy did not lead to clinical interventions)	4 weeks after cystoscopy
Specificity of high-stringency utDNA threshold	Specificity of a high-stringency utDNA threshold (at least 2 known urothelial cancer driver mutations with allele fraction > 5%) for clinically detectable urothelial cancer	1 year after diagnostic workup

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Characteristics of urothelial cancers that were not detected by the utDNA test	Characteristics of urothelial cancers that were not detected by the utDNA test (TNM pathological stage, World Health Organization (WHO) 2004/2016 grade, and tumor size)	Immediately after pathological examination of surgical tissue
Concordance between utDNA and urine cytology results	Concordance between utDNA and urine cytology results, with respect to positivity of the test	Immediately after completion of utDNA analysis and urine cytology

Collaborators and Investigators

• Sponsor: Tampere University Hospital
• Collaborators: Tampere University
• Investigators: Principal Investigator: Jussi Nikkola, Tampere University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 8, 2024
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2029

Study Registration Dates

• First Submitted: February 5, 2024
• First Submitted That Met QC Criteria: March 13, 2024
• First Posted (Actual): March 15, 2024

Study Record Updates

• Last Update Posted (Estimated): October 10, 2025
• Last Update Submitted That Met QC Criteria: October 8, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Keywords: Urine tumor DNA; Liquid biopsies; Bladder neoplasms; Urothelial neoplasms; Upper tract urothelial neoplasms
• 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; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Urologic Neoplasms; Carcinoma; Urinary Bladder Diseases; Urinary Bladder Neoplasms; Carcinoma, Transitional Cell
• Other Study ID Numbers: R21088B

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No