Clinical trial NCT06218433: Urothelial Cancer Screening in Individuals With Lynch Syndrome Using a Urine Tumor DNA Panel (LS-URO Study)
Official title: Urothelial Cancer Screening in Individuals With Lynch Syndrome Using a Urine Tumor DNA Panel (LS-URO Study)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
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
Lead sponsor: Tampere University Hospital
Sponsor class: OTHER
Collaborators: name: Tampere University
First posted: 2024-01-23
Enrollment: 200
Sex: ALL
Minimum age (years): 50
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: SCREENING

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.


Eligibility criteria: 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

Primary outcomes:
measure: Sensitivity and specificity of positive utDNA for urothelial cancer within one year of follow-up
timeFrame: At 1 years of follow-up
Secondary outcomes:
measure: Specificity of positive utDNA for urothelial cancer at the time of testing
timeFrame: After all patients with positive utDNA have been evaluated with cystoscopy and/or imaging
measure: Sensitivity and specificity of positive utDNA for urothelial cancer within multiple years of follow-up
timeFrame: At 2, 5, and 10 years of follow-up
measure: Overall survival
timeFrame: At 5 and 10 years of follow-up
measure: Urothelial cancer specific survival
timeFrame: At 3, 5 and 10 years of follow-up
measure: Time to metastatic urothelial cancer
timeFrame: At 5 and 10 years of follow-up
measure: Time to diagnosis of muscle invasive or high grade urothelial cancer
timeFrame: At 2, 5 and 10 years of follow-up
measure: Time to diagnosis of urothelial cancer
timeFrame: At 2, 5 and 10 years of follow-up
measure: TNM pathological stage of urothelial cancers
timeFrame: At 2, 5 and 10 years of follow-up
measure: Size of urothelial tumors
timeFrame: At 2, 5 and 10 years of follow-up
measure: Urothelial cancer grade
timeFrame: At 2, 5 and 10 years of follow-up
Other outcomes:
measure: Sensitivity and specificity of urine cytology
timeFrame: At 1 year of follow-up
measure: Association of utDNA fraction with time to diagnosis of urothelial cancer
timeFrame: At 2, 5 and 10 years of follow-up
measure: Prevalence of somatic second hit in MMR genes
timeFrame: At 1, 2, 5 and 10 years of follow-up
measure: Cost of utDNA screening
timeFrame: At 1, 2, 5 and 10 years of follow-up
Locations:
city: Vancouver
country: Canada
facility: Vancouver Prostate Centre
city: Tampere
country: Finland
facility: Tampere University Hospital and Tampere University
Study officials:
affiliation: Tampere University Hospital
name: Jussi Nikkola, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: