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

Not Applicable
Recruiting
Conditions
Urothelial Carcinoma
Lynch Syndrome
Interventions
Diagnostic Test: Urothelial cancer screening using urine tumor DNA test
Diagnostic Test: Urothelial cancer screening using urine cytology (comparator)
Registration Number
NCT06218433
Lead Sponsor
Tampere University Hospital
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
200
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 & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Screening armUrothelial cancer screening using urine tumor DNA testInvitation to participate in urothelial cancer screening and questionnaires
Screening armUrothelial cancer screening using urine cytology (comparator)Invitation to participate in urothelial cancer screening and questionnaires
Primary Outcome Measures
NameTimeMethod
Sensitivity and specificity of positive utDNA for urothelial cancer within one year of follow-upAt 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 Outcome Measures
NameTimeMethod
Size of urothelial tumorsAt 2, 5 and 10 years of follow-up

Maximum diameter of urothelial tumors found in utDNA positive and negative patients

Sensitivity and specificity of positive utDNA for urothelial cancer within multiple years of follow-upAt 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

Overall survivalAt 5 and 10 years of follow-up

Overall survival in utDNA positive and negative patients

Urothelial cancer specific survivalAt 3, 5 and 10 years of follow-up

Urothelial cancer specific survival survival in utDNA positive and negative patients

Time to metastatic urothelial cancerAt 5 and 10 years of follow-up

Time to metastatic urothelial cancer in utDNA positive and negative patients

Time to diagnosis of urothelial cancerAt 2, 5 and 10 years of follow-up

Time to diagnosis of urothelial cancer in utDNA positive and negative patients

Urothelial cancer gradeAt 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

Specificity of positive utDNA for urothelial cancer at the time of testingAfter 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

Time to diagnosis of muscle invasive or high grade urothelial cancerAt 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

TNM pathological stage of urothelial cancersAt 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

Trial Locations

Locations (2)

Vancouver Prostate Centre

🇨🇦

Vancouver, Canada

Tampere University Hospital and Tampere University

🇫🇮

Tampere, Finland

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