The Role of Universal Cancer Only Marker SIX6 in Diagnosing Non-Muscle Invasive Bladder Cancer

NCT07252297 | Active Not Recruiting DMC

• 2 other identifiers: XJLL-KY-202525092024JC-YBQN-0984
• Study Type: interventional
• Target: 177
• Locations: 1 country
• Sites: 1

Brief Summary

Transurethral resection of bladder tumor (TURBT) is the standard therapeutic approach for patients with non-muscle-invasive bladder cancer (NMIBC). Postoperative intravesical chemotherapy or BCG immunotherapy is commonly administered to prevent recurrence. However, limitations such as suboptimal specimen integrity and tissue artifacts from intraoperative cauterization may lead to inaccurate risk stratification in cases classified as low-risk NMIBC, complicating individualized prognostic assessment. Consequently, clinicians often resort to prolonged intravesical therapy to mitigate recurrence risk, resulting in substantial overtreatment. Previous studies in bladder cancer have demonstrated that detection of SIX6 gene methylation in urine enables noninvasive and accurate auxiliary diagnosis, with a sensitivity of 88.9%, specificity of 94.7%, and overall accuracy of 92.9%. In this retrospective case-control study, we aim to evaluate the utility of SIX6 methylation as an objective biomarker for predicting recurrence in patients with low-risk NMIBC.

Conditions

Non-muscle Invasive Bladder Cancer

Keywords

DNA methylation;; biomarker; diagnosis

Outcome Measures

Primary Outcomes (1)

• Difference in SIX6 methylation levels between recurrence and non-recurrence groups

  SIX6 gene promoter methylation level is measured as a continuous variable from post-operative tissue or urine DNA using quantitative methylation-specific PCR (qMSP). The values will be compared between the group of patients who later experience recurrence and the group who do not.

  At the time of initial TURBT surgery (baseline)

Secondary Outcomes (1)

• Diagnostic performance of SIX6 methylation for predicting recurrence

  Through study completion, up to 3 years

Study Arms (2)

SIX6 Positive

EXPERIMENTAL

Participants with low-risk NMIBC who test positive for SIX6 gene methylation in their post-operative tissue or urine sample. This cohort is observed prospectively for the outcome of tumor recurrence.

Diagnostic Test: SIX6 Gene Methylation Assay

SIX6 Methylation Negative

EXPERIMENTAL

Participants with low-risk NMIBC who test negative for SIX6 gene methylation in their post-operative tissue or urine sample. This cohort serves as the control and is observed prospectively for the outcome of tumor recurrence.

Diagnostic Test: SIX6 Gene Methylation Assay

Interventions

SIX6 Gene Methylation Assay DIAGNOSTIC_TEST

A molecular diagnostic test that detects the methylation status of the SIX6 gene promoter region in post-operative tissue or urine samples from patients with low-risk non-muscle-invasive bladder cancer (NMIBC). The test uses quantitative methylation-specific PCR to determine methylation levels, which are then used to classify patients into SIX6 methylation positive or negative groups for prognostic assessment of recurrence risk.

SIX6 Methylation Negative; SIX6 Positive

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• age higher than 18;
• patients diagnosis with non muscle invisive bladder cancer;
• willing to provide 100Ml urine before treatment;
• patients were diagnosis with bladder cancer for the first time

You may not qualify if:

• patiens have more than one tumors besides bladder cancer;
• pregnant women;
• unwilling to partipate the research -

Sponsors & Collaborators

• Xijing Hospital: lead

Study Sites (1)

Xi Jing Hopspital

Xi'an, ShannxI, 710300, China

Location

MeSH Terms

Conditions

Non-Muscle Invasive Bladder Neoplasms; Disease

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Urinary Bladder Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: This is a biomarker-based diagnostic study where participant grouping is determined by objective laboratory testing (SIX6 methylation status). Blinding of participants or investigators is not feasible due to the nature of the diagnostic assay.
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This study employs a parallel group design comparing two naturally occurring cohorts defined by SIX6 methylation status (positive vs. negative) in low-risk NMIBC patients, with prospective follow-up for recurrence outcomes.

Study Record Dates

• First Submitted: November 18, 2025
• First Posted: November 26, 2025
• Study Start: January 1, 2024
• Primary Completion (Estimated): December 30, 2026
• Study Completion (Estimated): December 30, 2026
• Last Updated: November 26, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)