Non-invasive Urinary Genomics-Based Risk Assessment for Early Urothelial Carcinoma Diagnosis

Henan Provincial People's Hospital800 enrolled

Overview

This is a two-stage, prospective, single-center observational diagnostic accuracy study evaluating noninvasive urine testing for the detection of urothelial carcinoma (UC). The study enrolls adult patients presenting with gross or microscopic hematuria and imaging evidence of a space-occupying lesion in the renal pelvis, ureter, or bladder, who are scheduled for diagnostic cystoscopy and/or surgical tissue sampling. Histopathological examination serves as the reference standard. Stage 1 (Completed, 8th October 2019 - 31st December 2023): A total of 113 participants have been enrolled. Owing to sufficient research funding, all participants in this stage underwent four urine-based tests: cytology, fluorescence in situ hybridization (FISH), DNA methylation, and a 17-gene mutation panel. Stage 2 (Ongoing, from 1st January 2024): The testing protocol was refined to focus on urine DNA methylation alone, owing to limited research funding and the lower cost of DNA methylation compared with the 17-gene mutation panel. As of registration (May 2026), approximately 330 participants have been enrolled. All enrolled participants are categorized into two groups based on histopathology: a UC group (including upper tract urothelial carcinoma \[UTUC\] and bladder cancer \[BC\]) and a non-UC control group. The primary outcome is the diagnostic accuracy (area under the receiver operating characteristic curve \[AUC\] with 95% confidence interval, sensitivity, and specificity) of the four urine-based tests in the Stage 1 cohort. The key secondary outcome is the diagnostic accuracy of urine DNA methylation in the Stage 2 cohort. Other secondary outcomes include paired comparisons of AUCs among the four tests in the Stage 1 cohort. Exploratory analyses will include the diagnostic performance of urine cytology in a subset of Stage 2 participants with UTUC, as well as subgroup analyses by tumor site (UTUC vs. BC). Because this study is purely observational and non-interventional, prospective registration was not a regulatory or institutional requirement when enrollment began in 2019. This record is being submitted prior to any data analysis to ensure consistency with current research transparency standards.

Study Type

OBSERVATIONAL

Enrollment

800

Conditions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: Patients are eligible if they meet all of the following criteria: 1. Age ≥ 18 years. 2. Presence of gross or microscopic hematuria. 3. Imaging (B-ultrasonography, CT, or MRI) showing a renal pelvic, ureteral, or bladder lesion. 4. Scheduled for surgery for tissue histopathological diagnosis. 5. Able to provide written informed consent. Exclusion Criteria 1. Inadequate urine sample (poor quality or insufficient volume). 2. Lack of final histopathological diagnosis.

Outcomes

Primary Outcomes

Diagnostic accuracy of four urine-based tests in the Stage 1 cohort

Area under the receiver operating characteristic curve (AUC) with 95% confidence interval (CI), sensitivity, and specificity of cytology, fluorescence in situ hybridization (FISH), DNA methylation, and a 17-gene mutation panel for the detection of urothelial carcinoma (UC) in the Stage 1 cohort, using histopathology as the reference standard.

Time frame: At the time of urine collection and subsequent histopathological diagnosis (within 4 weeks of urine collection)

Secondary Outcomes

Diagnostic accuracy of urine DNA methylation in the Stage 2 cohort

AUC with 95% CI, sensitivity, and specificity of urine DNA methylation for the detection of UC in all participants enrolled in Stage 2, using histopathology as the reference standard.

Time frame: At the time of urine collection and subsequent histopathological diagnosis (within 4 weeks of urine collection).

Paired comparisons of AUCs among the four tests in the Stage 1 cohort

Paired comparisons of areas under the ROC curves (AUCs) among cytology, FISH, DNA methylation, and the 17-gene mutation panel for detecting UC in the Stage 1 cohort.