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

ConditionsUrothelial Carcinoma Lynch Syndrome

Trial statusRecruiting

Trial phaseNot applicable

Trial typeInterventional

Biological sexAll

Age50-75

SponsorTampere University Hospital

About this trial

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.

Eligibility criteria

This trial accepts healthy volunteers

Qualifiers

Willing and able to provide informed consent

Diagnosis of Lynch syndrome

Age 50 - 75 years at study recruitment

Disqualifiers

Concurrent urothelial carcinoma

Trial design

Design model

Single group

Treatments tested in this trial

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

Treatment groups

200 Participants

are divided into 1 treatment group

Group A: Screening armExperimental treatment 2 interventions

Trial outcomes

Primary outcomes

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

Time frame

At 1 years of follow-up

Secondary outcomes

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

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 frame

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

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

Time frame

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

Overall survival

Overall survival in utDNA positive and negative patients

Time frame

At 5 and 10 years of follow-up

Urothelial cancer specific survival

Urothelial cancer specific survival survival in utDNA positive and negative patients

Time frame

At 3, 5 and 10 years of follow-up

Other outcomes

Sensitivity and specificity of urine cytology

Sensitivity and specificity of urine cytology for detecting urothelial cancer, using histologically verified cancers detected within 1 year of cytology as ground truth

Time frame

At 1 year of follow-up

Association of utDNA fraction with time to diagnosis of urothelial cancer

Association of utDNA fraction (quantified based on mutation allele fractions in urine DNA) with time to diagnosis of urothelial cancer

Time frame

At 2, 5 and 10 years of follow-up

Prevalence of somatic second hit in MMR genes

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

Time frame

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

Cost of utDNA screening

Analysis of the cost of utDNA screening, including cost per urothelial cancer found

Time frame

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

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Tampere University Hospital

Lead sponsor

Tampere University

Collaborator

Source ClinicalTrials.gov

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