Non-muscle-invasive bladder cancer (NMIBC) accounts for approximately 75% of newly diagnosed bladder cancers and is characterized by a high risk of recurrence and progression. Current guidelines recommend that patients with stage T1 NMIBC undergo a second transurethral resection of bladder tumor (re-TURBT) within 2-6 weeks after the initial surgery to remove residual tumor, confirm staging, and obtain additional pathological information. However, the benefits of routine re-TURBT for all high-risk patients remain controversial, as many patients may not have residual disease, while the procedure carries surgical and anesthetic risks, physical and psychological burden, and additional healthcare costs.
Urine tumor DNA (utDNA) refers to DNA fragments shed by tumor cells into urine. It can be detected using molecular assays with high sensitivity and specificity, offering a non-invasive method for bladder cancer diagnosis and surveillance. Previous studies have shown that positive utDNA results after initial TURBT may be associated with residual disease and higher recurrence risk.
This multicenter, randomized controlled trial aims to evaluate whether utDNA testing can accurately identify NMIBC patients who are most likely to benefit from re-TURBT, thereby guiding the decision to perform the procedure. The goal is to optimize patient selection for re-TURBT, reduce unnecessary surgeries, and improve patient quality of life while maintaining oncologic safety.
Male or female, aged 18 years or older.
Histologically confirmed non-muscle-invasive bladder tumor, with no evidence of muscle-invasive bladder cancer or metastatic disease.
Histologically confirmed urothelial carcinoma of the bladder or bladder tumor with urothelial carcinoma as the predominant component (>50%).
Incomplete initial transurethral resection of bladder tumor (TURBT) or suspected incomplete resection.
Contraindications to transurethral resection of bladder tumor (TURBT).
Concurrent malignancy of the upper urinary tract (ureter or renal pelvis).
Parallel
Second Transurethral Resection of Bladder Tumor (re-TURBT)
Procedure/SurgeryParticipants with NMIBC who have undergone initial TURBT will not receive utDNA testing and will undergo a second transurethral resection of bladder tumor (re-TURBT) within 2-6 weeks after the initial surgery, in accordance with current clinical guidelines.
utDNA Testing (Urine Tumor DNA Detection)
Diagnostic testParticipants with NMIBC who have undergone initial TURBT will receive urine tumor DNA (utDNA) testing. If utDNA is positive, the patient will undergo a second transurethral resection of bladder tumor (re-TURBT) within 2-6 weeks after the initial surgery. If utDNA is negative, re-TURBT will be omitted and patients will proceed to guideline-based adjuvant therapy or surveillance.
Recurrence-free survival (RFS)
Time from randomization to the first documented event of bladder tumor recurrence (any grade), upper tract urothelial recurrence.
Progression-free survival (PFS)
Time from initial TURBT to disease progression (development of muscle-invasive bladder cancer, distant metastasis).
Pathological outcomes of second transurethral resection (re-TURBT)
Proportion of patients with residual tumor, upstaging (higher T category at re-TURBT), or concomitant CIS among those undergoing repeat TURBT.
Patient-reported outcomes
Health outcomes directly reported by the patient without interpretation by clinicians or others. These measures capture patients' perceptions of symptoms, functional status, health-related quality of life (HRQoL), and treatment-related burden.
Correlation Between utDNA Status and Clinical Outcomes
Association of urine utDNA results with cystoscopy findings, imaging results, and re-TURBT pathology; evaluation of diagnostic performance (sensitivity, specificity, predictive values, AUC) and relation to recurrence/progression.
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