Sequential Gemcitabine Plus Docetaxel Versus Gemcitabine Plus Mitomycin C for BCG-Unresponsive Non-Muscle-Invasive Bladder Cancer

High-grade BCG-unresponsive non-muscle-invasive bladder cancer remains a major therapeutic challenge. Radical cystectomy is considered the standard treatment; however, many patients are unwilling or medically unfit to undergo surgery. Sequential intravesical chemotherapy has emerged as a bladder-preserving treatment strategy with encouraging oncological outcomes.

This prospective, randomized, open-label, single-center phase II trial is designed to compare the efficacy and safety of two sequential intravesical chemotherapy regimens following complete TURBT.

Eligible patients with histologically confirmed BCG-unresponsive high-grade NMIBC will be randomized in a 1:1 ratio to receive either sequential intravesical gemcitabine followed by docetaxel or sequential intravesical gemcitabine followed by mitomycin C.

Both treatment regimens consist of a six-week induction course followed by monthly maintenance instillations for twelve months according to the study protocol. Clinical follow-up includes cystoscopy, urine cytology, pelvic ultrasonography, adverse event assessment according to CTCAE criteria, and quality-of-life evaluation using the EORTC QLQ-C30 and EORTC QLQ-NMIBC24 questionnaires.

The primary endpoint is 12-month event-free survival. Secondary endpoints include cystectomy-free survival, progression-free survival, safety, tolerability, and comparative efficacy of both treatment strategies.

A total of 228 participants will be enrolled. Statistical analyses will be performed according to the intention-to-treat principle using Kaplan-Meier survival analysis, log-rank testing, and Cox proportional hazards regression.

Inclusion criteria

• Age ≥18 years.
• Histologically confirmed BCG-unresponsive non-muscle-invasive urothelial bladder cancer (NMIBC).
• Complete transurethral resection of bladder tumor (TURBT) before study treatment.
• Intermediate- or high-risk NMIBC according to current clinical guidelines.
• Candidate for intravesical chemotherapy.
• ECOG performance status 0-2.
• Adequate hematologic, renal, and hepatic function.
• Written informed consent.

Exclusion criteria

• Muscle-invasive (≥T2), locally advanced, or metastatic urothelial carcinoma.
• Upper urinary tract urothelial carcinoma requiring treatment.
• Previous hypersensitivity to gemcitabine, docetaxel, mitomycin C, or formulation components.
• Active uncontrolled urinary tract infection.
• Pregnancy or breastfeeding.
• Concurrent participation in another interventional clinical trial.
• Any serious uncontrolled medical condition that, in the investigator's opinion, would interfere with study participation or interpretation of results.