Need for a second transurethral resection in high-risk NMIBC patients with negative urine genome-wide low-depth sequencing after initial resection

A Prospective, Multicenter, Randomized Study Comparing the Necessity of a Second Transurethral Resection in High-Risk Non-Muscle-Invasive Bladder Cancer Patients With Negative Results From Post-Initial Resection Urine Genome-Wide Low-Depth Sequencing

This trial will test whether people with high-risk non-muscle-invasive bladder cancer who have a negative urine genome-wide low-depth sequencing result can safely skip a planned second transurethral resection.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 428 (estimated)
• Ages: 18 Years to 80 Years
• Sex: All
• Sponsor: The First Affiliated Hospital with Nanjing Medical University (Academic / other)
• Locations: 1 site (Nanjing, Jiangsu)
• Trial ID: NCT07036731 on ClinicalTrials.gov

What this trial studies

This is a prospective, randomized, multicenter trial enrolling about 428 adults with non-muscle-invasive bladder cancer who are scheduled for a planned second transurethral resection (reTURBT) after an initial TURBT. Between 1 and 6 weeks after the first resection, participants provide a 100 ml urine sample for urinary sediment DNA extraction and genome-wide low-depth sequencing at a central laboratory. Patients with a positive sequencing result will proceed to the second resection, while those with a negative result are randomized 1:2 to either omit the second resection or undergo the planned resection. All participants are followed for two years for recurrence and related outcomes to compare safety and recurrence-free survival between pathways.

Who should consider this trial

Good fit: Adults (≥18) with non-muscle-invasive bladder cancer who have completed an initial TURBT and are scheduled for reTURBT because of incomplete resection, absence of muscle in the specimen, T1 stage, or G3/high-grade disease (excluding pure CIS), and who can provide a 100 ml urine sample and consent to follow-up are the intended participants.

Not a fit: Patients with a positive urine sequencing result, those with other non-urothelial malignancies, or those unable to provide the required urine sample or follow-up are unlikely to avoid the second resection and therefore may not benefit from this approach.

Why it matters

Potential benefit: If successful, the approach could allow some high-risk NMIBC patients to avoid an unnecessary second surgery, reducing operative risks, recovery time, and healthcare costs.

How similar studies have performed: Prior work on urine-based biomarkers and genomic assays for NMIBC surveillance has been promising for detection and monitoring, but using genome-wide low-depth urinary sequencing specifically to omit a second TURBT is a relatively new strategy with limited prior validation.

Eligibility criteria

Inclusion Criteria:

* Patients with NMIBC who have completed the initial transurethral resection and are scheduled for a second resection, as recommended by guidelines or physician's choice:

  1. Incomplete initial TURBT due to various reasons (including large tumor size, high risk of intraoperative bleeding, extensive tumor range, etc.), posing a risk of residual tumor;
  2. Absence of muscle layer tissue in the initial resection specimen;
  3. Post-initial resection pathology indicating T1 stage;
  4. Post-initial resection pathology indicating G3/high-grade tumor, excluding pure carcinoma in situ;
* Ability to provide a 100ml routine urine sample within 1-6 weeks after the initial resection and before the second resection;
* Age ≥ 18 years;
* Willingness to provide basic clinical information, pathology, and subsequent - recurrence monitoring results;
* Willingness to sign the informed consent form.

Exclusion Criteria:

* Patients with other non-urothelial malignant tumors (including prostate cancer and renal cell carcinoma);
* Patients previously diagnosed with muscle-invasive bladder cancer;
* Patients unable to undergo a second resection;
* Patients with incomplete pathological information of the sample;
* Patients with contaminated samples;
* Patients whose urine samples fail quality control for valid reasons and cannot be resampled;
* Any condition deemed by the investigator as potentially harming the subject or preventing the subject from meeting or fulfilling the study requirements;
* Patients unable to provide written informed consent.

Where this trial is running

Nanjing, Jiangsu

• The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029 — Nanjing, Jiangsu, China (Recruiting)

Study contacts

• Study coordinator: Yang xiao, PhD

Conditions Non Muscle Invasive Bladder Cancer; reTURBT; NMIBC; urine biomarker; RFS