Genetic Testing in Upper Tract Urothelial Carcinoma (UTUC): the Epicheck Study

Study Overview
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Brief Summary
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Background: Upper tract urothelial carcinoma (UTUC) is a rare tumor associated with bladder cancer in up to 50% of cases. Its incidence is rising due to improved detection and bladder cancer survival. The diagnosis of UTUC is challenging because more than 35% of the standard biopsies can result inconclusive. The grading of UTUC cells, which delivers the most important data for the choice between a kidney-sparing surgery (KSS) and a radical treatment, is upgraded in 30% of radical nephroureterectomies. The follow-up of UTUC after KSS requires an invasive procedure as a diagnostic ureteroscopy for a minimum of 5 years, and urinary cytology has low diagnostic power. Objective: The aim of the study is to evaluate the accuracy (overall and stratified for grade) of a DNA methylation urine biomarker test (Bladder EpiCheckTM) in UTUC, and to compare it with current standard (urinary cytology). The secondary objective is to show its applicability in the specific clinical scenario of UTUC surveillance after kidney-sparing surgery and related cost-effectiveness. Design, Setting, and Participants: From February 2019 to February 2021, 80 consecutive patients candidates to ureteroscopy for suspicion of primary, recurrent or metachronous UTUC in one tertiary Referral Centers (Fundaciò Puigvert) giving written informed consent will be included in the study. Intervention: Bladder urine samples (> 10 ml) will be collected for cytology and for the methylation test before cystoscopy. Prior to semirigid and flexible ureteroscopy, urine specimens from the upper urinary tract will be obtained via a ureteral catheter.

Official Title
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Genetic Testing in Upper Tract Urothelial Carcinoma (UTUC): the Epicheck Study

Conditions
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Urologic Cancer, Urologic Neoplasms

Intervention / Treatment
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* Diagnostic Test: Urine biomarker


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients suspected for primary or recurrent upper tract urothelial cancer requiring ureteroscopy Exclusion Criteria: Metastatic disease with patient unfit for ureteroscopy Positive cystoscopy (concomitant presence of bladder cancer) Macroscopic hematuria not self-limiting requiring upfront nephroureterectomy

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|Diagnostic Test: Urine biomarker|Bladder urine samples (> 10 ml) will be collected for cytology and for the methylation test before cystoscopy. Prior to semirigid and flexible ureteroscopy, urine specimens from the upper urinary tract will be obtained via a ureteral catheter.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sensitivity, specificity, positive predictive value and negative predictive value of the test | To test the accuracy of the urine biomarker | Through study completion, an average of 1 year | 
| Comparison with urinary cytology | To evaluate and compare performance of urinary cytology and urine biormarker | Through study completion, an average of 1 year | 
| Evaluation of biormarker performance in bladder and upper tract | To compare the accuracy of the test in situ (upper tract) and in the bladder | Through study completion, an average of 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| High grade/low grade tumors diagnosis | Sub-analysis on biormaker accuracy for low and high grade tumours | Through study completion, an average of 1 year | 
| Impact of the urine biormaker for UTUC diagnosis | A decision-making analysis will be performed in patients with UTUC suspicion, reporting the net benefit, the number of unnecessary ureteroscopies avoided | Through study completion, an average of 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Upper tract urothelial carcinoma, Urinary biomarker, Liquid biopsy, Epigenetics, Surveillance, Follow-up