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

NCT06218433 | Recruiting

• 1 other identifier: R22125
• Study Type: interventional
• Target: 200
• Locations: 2 countries
• Sites: 2

Brief Summary

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.

Conditions

Urothelial Carcinoma; Lynch Syndrome

Keywords

Lynch syndrome; Hereditary cancer syndrome; Screening; Urothelial neoplasms; Bladder neoplasms; Upper tract urothelial neoplasms; Urogenital diseases; Liquid biopsies; Urine tumor DNA

Outcome Measures

Primary Outcomes (1)

• Sensitivity and specificity of positive utDNA for urothelial cancer within one year 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 Outcomes (10)

• Specificity of positive utDNA for urothelial cancer at the time of testing

  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

  At 2, 5, and 10 years of follow-up

• Overall survival

  At 5 and 10 years of follow-up

• Urothelial cancer specific survival

  At 3, 5 and 10 years of follow-up

• Time to metastatic urothelial cancer

  At 5 and 10 years of follow-up

Other Outcomes (4)

• Sensitivity and specificity of urine cytology

  At 1 year of follow-up

• Association of utDNA fraction with time to diagnosis of urothelial cancer

  At 2, 5 and 10 years of follow-up

• Prevalence of somatic second hit in MMR genes

  At 1, 2, 5 and 10 years of follow-up

Study Arms (1)

Screening arm

EXPERIMENTAL

Invitation to participate in urothelial cancer screening and questionnaires

Diagnostic Test: Urothelial cancer screening using urine tumor DNA test; Diagnostic Test: Urothelial cancer screening using urine cytology (comparator)

Interventions

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

Screening arm

Urothelial cancer screening using urine cytology (comparator) DIAGNOSTIC_TEST

Urine cytology sample

Screening arm

Eligibility Criteria

• Age: 50 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• Concurrent urothelial carcinoma

Sponsors & Collaborators

• Tampere University Hospital: lead
• Tampere University: collaborator

Study Sites (2)

Vancouver Prostate Centre

Vancouver, Canada

RECRUITING

Tampere University Hospital and Tampere University

Tampere, Finland

RECRUITING

MeSH Terms

Conditions

Carcinoma, Transitional Cell; Colorectal Neoplasms, Hereditary Nonpolyposis; Neoplastic Syndromes, Hereditary; Urinary Bladder Neoplasms; Urogenital Diseases

Condition Hierarchy (Ancestors)

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

Study Officials

• Jussi Nikkola, MD, PhD

  Tampere University Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jussi Nikkola, MD, PhD

CONTACT

03311611; jussi.nikkola@fimnet.fi

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: SCREENING
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 10, 2024
• First Posted: January 23, 2024
• Study Start: April 10, 2023
• Primary Completion (Estimated): December 30, 2026
• Study Completion (Estimated): December 31, 2034
• Last Updated: November 18, 2025

Record last verified: 2025-11

Locations

FI (1); CA (1)