High-risk non-muscle-invasive bladder cancer (NMIBC) carries a substantial risk of residual disease after initial transurethral resection of bladder tumor (TURBT). Current guidelines recommend a second TURBT (re-TURBT) within 2-6 weeks for patients with stage T1 disease to remove residual tumor, confirm staging, and obtain additional pathological information. However, the actual survival benefit of routine re-TURBT for all high-risk patients remains debated, and the procedure may pose surgical risks, increase healthcare costs, and impact patient quality of life.

Urine tumor DNA (utDNA) and urine tumor RNA (utRNA) are molecular biomarkers detectable through non-invasive "liquid biopsy" methods. In urothelial carcinoma, tumor-derived nucleic acids can be shed into urine, where they can be detected with high sensitivity and specificity. These biomarkers may help identify patients most likely to harbor residual disease after initial TURBT, and thus most likely to benefit from re-TURBT.

This prospective, open-label, observational, single-center study aims to evaluate the clinical value of utDNA/utRNA testing in guiding re-TURBT for patients with high-risk NMIBC. The study will assess whether molecular urine testing can improve patient selection for re-TURBT, potentially reducing unnecessary procedures while maintaining oncological safety.

Inclusion Criteria:

Participants must meet all of the following criteria to be eligible for the study:

1. Male or female, aged 18 years or older.

2. Histologically confirmed non-muscle-invasive bladder tumor, with no evidence of muscle-invasive bladder cancer or metastatic disease.

3. Histologically confirmed urothelial carcinoma of the bladder or bladder tumor with urothelial carcinoma as the predominant component (>50%).

4. At least one of the following conditions:

   1. Incomplete initial transurethral resection of bladder tumor (TURBT) or suspected incomplete resection.
   2. Absence of detrusor muscle in the initial TURBT pathological specimen (except for low-grade Ta stage tumors or carcinoma in situ [CIS]).
   3. T1 stage tumor.

5. Willingness to provide a 50 mL urine sample between 2-6 weeks after the initial TURBT and prior to re-TURBT.

6. Willingness to provide tumor tissue samples for pathological examination.

7. Willingness to undergo genetic testing required for the trial.

8. Voluntarily agrees to participate in the study, has signed informed consent, demonstrates good compliance, and is willing to complete study follow-up.

Exclusion Criteria:

1. Contraindications to transurethral resection of bladder tumor (TURBT).
2. Concurrent malignancy of the upper urinary tract (ureter or renal pelvis).

Adults (≥18 years) with histologically confirmed high-risk non-muscle-invasive bladder cancer (NMIBC) who have undergone initial transurethral resection of bladder tumor (TURBT) and are scheduled for second TURBT. Eligible tumors are urothelial carcinoma or bladder tumors with urothelial carcinoma as the predominant component (>50%), with no evidence of muscle-invasive or metastatic disease.