Personalized Urine Biomarker for Patients With Bladder Cancer

Personalized Urine Biomarker for Patients With Bladder Cancer: Pilot Study

Introduction

Bladder cancer is the most common malignancy involving the urinary system and the ninth most common malignancy worldwide. Urothelial carcinoma is accounts for approximately 90 percent of bladder cancers in the western world.

In the United States, approximately 80,000 new cases and 17,000 deaths occur each year due to bladder cancer.

Approximately 75% of patients present with superficial disease (Ta and T1), while 25% present with muscle invasive (T2 or greater) disease. Overall, 70% of treated tumors recur, with 30% of recurrent tumors progressing to muscle invasive disease.

The majority of these patients have a recurrence after endoscopic resection, thus lifelong surveillance with periodically cystoscopy is recommended. Cystoscopy, which is the "gold standard" for the detection of bladder cancer, is an expensive and invasive procedure, and it also can miss a flat lesion, especially carcinoma in situ which is considered a high grade malignant condition, therefore better follow-up tools should be developed in order to address those issues.

Voided urinary cytology is a useful noninvasive adjunct to cystoscopy due to its high specificity, more than 90%. Although it has a high sensitivity at detecting high-grade lesions, between 80 to 90%,, in low-grade its sensitivity is very low, between 20 to 50%. Amongst the non-muscle-invasive, low grade tumors will progress to muscle-invasive or metastatic cancer at approximately 10% and roughly a third of high-grade tumors progress, therefore, close monitoring and early detection of all lesions are important for management, and noninvasive tumor markers with high accuracy for the detection of all grades of urothelial carcinoma will significantly reduce patient cost, anxiety and morbidity.

Cystoscopy in combination with cytology remains the most effective means of detecting bladder cancer. However, cystoscopy is an invasive procedure, and while cytology remains a useful method for detecting high grade tumors, its utility in detecting low grade tumors remains limited due to the lack of distinguishing cytological features between low grade disease and reactive processes. Currently there are several markers available or under investigation for the detection and monitoring/surveillance of bladder cancer, most of them have higher sensitivities, especially when used to identify low grade disease, but with lower specificities when compared to cytology. Furthermore, all of these tests must still be utilized in conjunction with cystoscopy findings.

Recently, cell-free DNA (cfDNA) isolated from urine supernatant has been shown to have great potential in bladder cancer detection and surveillance. Bladder cancer exhibits unique genetic features that can be identified from sequencing and expression of cfDNA.

Aim of study:

The aim of this study is to establish a method for a personalized urinary biomarker with the usage of well explored urothelail cancer genetic mutations in urine cfDNA, for the detection of bladder cancer presence.

Study Overview

• Status: Not yet recruiting
• Conditions: Bladder Neoplasm
• Intervention / Treatment: Procedure: TURBT

• Study Type: Observational
• Enrollment (Anticipated): 20

Contacts and Locations

• Study Contact: Name: Ran Katz, MD; Phone Number: +972-4-8629775; Email: rank@ziv.gov.il

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

• Sampling Method: Non-Probability Sample

Study Population

The study will include 20 participants of patients with urothelial cancer of bladder who are planned for TURBT procedure.

Description

Inclusion Criteria:

• Age 18+ years old
• Able to give a written consent
• Able to provide a minimum of 60 mL of urine prior to undergoing transurethral resection of bladder tumor (TURBT)
• Presence of a bladder tumor

Exclusion Criteria:

• Active urinary infection
• Macro-hematuria
• Inadequate material for testing
• Benign bladder tumor

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Presence of somatic mutations in bladder tumor cells	A set of selected somatic mutations will be checked against extracted urine cell free DNA from patients with bladder cancer, then a profile for each patient will be performed separately	24 months

Collaborators and Investigators

• Sponsor: Ziv Hospital

Study record dates

Study Major Dates

• Study Start (Anticipated): August 1, 2022
• Primary Completion (Anticipated): August 1, 2024
• Study Completion (Anticipated): August 1, 2025

Study Registration Dates

• First Submitted: February 21, 2022
• First Submitted That Met QC Criteria: July 17, 2022
• First Posted (Actual): July 20, 2022

Study Record Updates

• Last Update Posted (Actual): July 20, 2022
• Last Update Submitted That Met QC Criteria: July 17, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Keywords: bladder neoplasm, urine, biomarker
• Additional Relevant MeSH Terms: Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Urologic Diseases; Urinary Bladder Diseases; Urinary Bladder Neoplasms
• Other Study ID Numbers: 0121-21-ZIV

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No