Urothelial Cancer Screening in Individuals With Lynch Syndrome Using a Urine Tumor DNA Panel (LS-URO Study)

November 17, 2025 updated by: Tampere University Hospital
Lynch syndrome (LS) is an inherited cancer predisposition syndrome caused by pathogenic germline variants in DNA mismatch repair (MMR) genes. New cancer screening and diagnostic tools are urgently needed to identify LS-related cancers early enough for curative treatment. Urothelial cancers (comprising bladder and upper tract urothelial tumors) are the third most common cancer after colorectal and endometrial cancers in individuals with LS. Up to one in four LS individuals will develop urothelial cancer during their lifetime, with the risk varying based on the defective MMR gene. In this clinical trial, we will employ urine tumor DNA (utDNA) to identify asymptomatic urothelial cancers in Lynch syndrome patients, and to investigate the potential benefits of urine tumor DNA based screening in this high-risk population.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

200

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Canada
      • Vancouver, Canada
        • Recruiting
        • Vancouver Prostate Centre
        • Principal Investigator:
          • Peter Black
        • Contact:
          • Peter Black
  • Finland
      • Tampere, Finland
        • Recruiting
        • Tampere University Hospital and Tampere University
        • Contact:
          • Jussi Nikkola
        • Principal Investigator:
          • Jussi Nikkola
        • Principal Investigator:
          • Matti Annala
        • Principal Investigator:
          • Jukka-Pekka Mecklin
        • Principal Investigator:
          • Toni Seppälä

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  • Willing and able to provide informed consent
  • Diagnosis of Lynch syndrome
  • Age 50 - 75 years at study recruitment

Exclusion Criteria:

  • Concurrent urothelial carcinoma

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Screening
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Screening arm
Invitation to participate in urothelial cancer screening and questionnaires
Diagnostic test: Urothelial cancer screening using urine tumor DNA test
Urine sample DNA is analyzed using a targeted sequencing panel encompassing the coding regions of 21 genes that are recurrently mutated in urothelial cancer
Diagnostic test: Urothelial cancer screening using urine cytology (comparator)
Urine cytology sample

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Sensitivity and specificity of positive utDNA for urothelial cancer within one year of follow-up
Time Frame: At 1 years of follow-up
Sensitivity and specificity of positive utDNA for urothelial cancer, using histologically verified cancers detected within 1 year of the utDNA test as ground truth
At 1 years of follow-up

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Specificity of positive utDNA for urothelial cancer at the time of testing
Time Frame: After all patients with positive utDNA have been evaluated with cystoscopy and/or imaging
Specificity of positive utDNA test for urothelial cancer, using histologically verified cancers detected in the cystoscopy and/or imaging performed due to positive utDNA test as the ground truth
After all patients with positive utDNA have been evaluated with cystoscopy and/or imaging
Sensitivity and specificity of positive utDNA for urothelial cancer within multiple years of follow-up
Time Frame: At 2, 5, and 10 years of follow-up
Sensitivity and specificity of positive utDNA for urothelial cancer, using histologically verified cancers detected within 2, 5, and 10 years of the utDNA test as ground truth
At 2, 5, and 10 years of follow-up
Overall survival
Time Frame: At 5 and 10 years of follow-up
Overall survival in utDNA positive and negative patients
At 5 and 10 years of follow-up
Urothelial cancer specific survival
Time Frame: At 3, 5 and 10 years of follow-up
Urothelial cancer specific survival survival in utDNA positive and negative patients
At 3, 5 and 10 years of follow-up
Time to metastatic urothelial cancer
Time Frame: At 5 and 10 years of follow-up
Time to metastatic urothelial cancer in utDNA positive and negative patients
At 5 and 10 years of follow-up
Time to diagnosis of muscle invasive or high grade urothelial cancer
Time Frame: At 2, 5 and 10 years of follow-up
Time to diagnosis of muscle invasive or high grade urothelial cancer in utDNA positive and negative patients
At 2, 5 and 10 years of follow-up
Time to diagnosis of urothelial cancer
Time Frame: At 2, 5 and 10 years of follow-up
Time to diagnosis of urothelial cancer in utDNA positive and negative patients
At 2, 5 and 10 years of follow-up
TNM pathological stage of urothelial cancers
Time Frame: At 2, 5 and 10 years of follow-up
TNM pathological stage (American Joint Committee on Cancer (AJCC)/International Union Against Cancer (UICC)) of urothelial cancers found in utDNA positive and negative patients
At 2, 5 and 10 years of follow-up
Size of urothelial tumors
Time Frame: At 2, 5 and 10 years of follow-up
Maximum diameter of urothelial tumors found in utDNA positive and negative patients
At 2, 5 and 10 years of follow-up
Urothelial cancer grade
Time Frame: At 2, 5 and 10 years of follow-up
The World Health Organization (WHO) 2004/2016 grading of urothelial cancers found in utDNA positive and negative patients
At 2, 5 and 10 years of follow-up

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Sensitivity and specificity of urine cytology
Time Frame: At 1 year of follow-up
Sensitivity and specificity of urine cytology for detecting urothelial cancer, using histologically verified cancers detected within 1 year of cytology as ground truth
At 1 year of follow-up
Association of utDNA fraction with time to diagnosis of urothelial cancer
Time Frame: At 2, 5 and 10 years of follow-up
Association of utDNA fraction (quantified based on mutation allele fractions in urine DNA) with time to diagnosis of urothelial cancer
At 2, 5 and 10 years of follow-up
Prevalence of somatic second hit in MMR genes
Time Frame: At 1, 2, 5 and 10 years of follow-up
Prevalence of somatic second hit and additional somatic hits in mismatch repair genes (MSH2, MSH6, MLH1, PMS2) in Lynch syndrome patients diagnosed with urothelial cancer
At 1, 2, 5 and 10 years of follow-up
Cost of utDNA screening
Time Frame: At 1, 2, 5 and 10 years of follow-up
Analysis of the cost of utDNA screening, including cost per urothelial cancer found
At 1, 2, 5 and 10 years of follow-up

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Tampere University Hospital

Collaborators

Tampere University

Investigators

  • Principal Investigator: Jussi Nikkola, MD, PhD, Tampere University Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 10, 2023

Primary Completion (Estimated)

December 30, 2026

Study Completion (Estimated)

December 31, 2034

Study Registration Dates

First Submitted

January 10, 2024

First Submitted That Met QC Criteria

January 22, 2024

First Posted (Actual)

January 23, 2024

Study Record Updates

Last Update Posted (Actual)

November 18, 2025

Last Update Submitted That Met QC Criteria

November 17, 2025

Last Verified

November 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • R22125 (Other Identifier: Tampere University Hospital)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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