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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
SCREENING
Masking
NONE
Enrollment
200
Urine sample DNA is analyzed using a targeted sequencing panel encompassing the coding regions of 21 genes that are recurrently mutated in urothelial cancer
Urine cytology sample
Vancouver Prostate Centre
Vancouver, Canada
RECRUITINGTampere University Hospital and Tampere University
Tampere, Finland
RECRUITINGSensitivity 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
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
Time to metastatic urothelial cancer
Time to metastatic urothelial cancer in utDNA positive and negative patients
Time frame: At 5 and 10 years of follow-up
Time to diagnosis of muscle invasive or high grade urothelial cancer
Time to diagnosis of muscle invasive or high grade urothelial cancer in utDNA positive and negative patients
Time frame: At 2, 5 and 10 years of follow-up
Time to diagnosis of urothelial cancer
Time to diagnosis of urothelial cancer in utDNA positive and negative patients
Time frame: At 2, 5 and 10 years of follow-up
TNM pathological stage of urothelial cancers
TNM pathological stage (American Joint Committee on Cancer (AJCC)/International Union Against Cancer (UICC)) of urothelial cancers found in utDNA positive and negative patients
Time frame: At 2, 5 and 10 years of follow-up
Size of urothelial tumors
Maximum diameter of urothelial tumors found in utDNA positive and negative patients
Time frame: At 2, 5 and 10 years of follow-up
Urothelial cancer grade
The World Health Organization (WHO) 2004/2016 grading of urothelial cancers found in utDNA positive and negative patients
Time frame: At 2, 5 and 10 years of follow-up
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