Performance Evaluation of a Urine-based Methylation Assay for Urothelial Carcinoma

Performance Evaluation of a Urine-based Methylation Assay for Urothelial Carcinoma in Patients With Hematuria: A Prospective, Multi-center Cohort Study

Urothelial carcinoma (UC) is the most common malignancy of the urinary system. Hematuria is a significant clinical manifestation of UC, often diagnosed through invasive procedures. Urine DNA methylation testing is a promising non-invasive method for early UC detection. To evaluate the sensitivity and specificity of urine DNA methylation testing for detecting UC, using standard clinical and pathological diagnoses as the gold standard.

Urothelial carcinoma (UC) is the most common malignancy of the urinary system, and early detection and diagnosis are crucial for patient prognosis. Hematuria is a significant clinical manifestation of UC, but its diagnosis often relies on invasive procedures and imaging, posing a substantial burden on patients. With the advancement of molecular biology techniques, urine DNA methylation testing has emerged as a non-invasive and highly sensitive method for early UC detection. This study aims to evaluate the performance of urine DNA methylation testing in detecting UC in patients with hematuria.

All patients with hematuria will receive standard clinical diagnosis, including examinations, tests, surgeries, and pathological assessments to determine the presence of UC. These clinical diagnoses will serve as the gold standard to evaluate the sensitivity and specificity of urine DNA methylation testing in detecting UC in patients with hematuria.

To ensure accuracy and reliability of the results, select a subset of samples with known test results for external methylation sequencing. Authorized researchers will unblind the samples, and the statistical team will analyze the results, calculating sensitivity, specificity, positive predictive value, and negative predictive value of the urine DNA methylation test.

Inclusion Criteria:

• Aged between 18 and 90 years, with gross or microscopic hematuria.
• Able to provide enough urine for testing before surgery.
• Consent to participate in the study and sign the informed consent form.

Exclusion Criteria:

• With history of any malignancies (including Urothelial carcinoma).
• Severe urinary tract infection leading to sepsis.
• Patients with indwelling catheters, nephrostomy, or cystostomy.
• Severe liver or kidney failure or other conditions deemed unsuitable for the study.
• Samples with insufficient DNA content or other quality control failures.
• Incomplete clinical or pathological data.
• Patients currently undergoing intravesical or systemic chemotherapy, radiotherapy, immunotherapy, or targeted therapy.