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NCT Number: NCT06218433

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

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.

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Key information

Conditions

Urothelial Carcinoma Carcinoma Carcinoma, Transitional Cell Colonic Diseases Colorectal Neoplasms Colorectal Neoplasms, Hereditary Nonpolyposis Congenital, Hereditary, and Neonatal Diseases and Abnormalities DNA Repair-Deficiency Disorders Digestive System Diseases Digestive System Neoplasms Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Gastrointestinal Diseases Gastrointestinal Neoplasms Genetic Diseases, Inborn Intestinal Diseases Intestinal Neoplasms Lynch Syndrome Male Urogenital Diseases Metabolic Diseases Neoplasms Neoplasms by Histologic Type Neoplasms by Site Neoplasms, Glandular and Epithelial Neoplastic Syndromes, Hereditary Nutritional and Metabolic Diseases Urinary Bladder Diseases Urinary Bladder Neoplasms Urogenital Diseases Urogenital Neoplasms Urologic Diseases Urologic Neoplasms

Age range

50 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Vancouver Prostate Centre, Vancouver, Canada

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Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Urothelial cancer screening using urine tumor DNA test

Diagnostic 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

Urothelial cancer screening using urine cytology (comparator)

Diagnostic Test

Urine cytology sample

Primary outcomes

  1. 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

Secondary outcomes

  1. 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

  2. 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

  3. Overall survival

    Time frame: At 5 and 10 years of follow-up

    Overall survival in utDNA positive and negative patients

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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

Other outcomes

  1. 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

  2. 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

  3. 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

  4. 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

Study contacts

Contact information is provided by the study sponsor or research team.

Jussi Nikkola, MD, PhD

CONTACT

[email protected]

03311611 ext. +358

Sponsors and collaborators

Lead sponsor

Tampere University Hospital

Other

Collaborators

  • Tampere University

Registry information

Important dates

Study start
2023
Primary completion
2026
Study completion
2034
First posted
Jan 23, 2024
Registry last updated
Nov 18, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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