Is Prolonged Systemic Immunotherapy Necessary After Achieving Tumor-free Status in Patients With Extensive Transurethrally Unresectable Very-high-risk NMIBC?

Inclusion criteria

• Has histologically confirmed very-high-risk non-muscle-invasive urothelial carcinoma of the bladder.
• Has transurethrally unresectable bladder tumor, defined as visually incomplete TURBT and/or extensive high-volume disease considered unsuitable for complete and oncologically adequate transurethral resection.
• Has undergone cystoscopy and TURBT evaluation before study enrollment.
• Has received systemic PD-1/PD-L1 inhibitor-based bladder-sparing therapy before randomization.
• Has achieved tumor-free status before randomization, defined as:

• No visible bladder tumor on cystoscopy;
• Negative bladder biopsy and/or TURBT pathology;
• Negative urine cytology;
• Negative urinary tumor DNA (utDNA);
• No radiographic evidence of progression or metastasis.
• Has Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
• Has adequate organ function.
• Has provided written informed consent.

Cohort A Only

• Achieved tumor-free status at the initial response evaluation after induction systemic therapy.
• Maintained tumor-free status after additional systemic therapy before randomization.

Cohort B Only

• Did not achieve tumor-free status at the initial response evaluation because of residual non-muscle-invasive disease.
• Subsequently underwent complete TURBT/resection of residual disease followed by additional systemic therapy.
• Achieved tumor-free status at the second response evaluation before randomization.

Exclusion criteria

• Has muscle-invasive bladder cancer (≥T2), locally advanced unresectable disease, nodal disease, or distant metastasis.
• Has concurrent upper tract urothelial carcinoma.
• Has persistent visible tumor, positive bladder pathology, positive urine cytology, or positive utDNA before randomization.
• Has received prior systemic immunotherapy for metastatic urothelial carcinoma.
• Has active autoimmune disease requiring systemic treatment.
• Is receiving systemic immunosuppressive therapy.
• Has uncontrolled infection requiring systemic therapy.
• Has another active malignancy requiring systemic treatment.
• Has known active hepatitis B, hepatitis C, human immunodeficiency virus infection, or active tuberculosis.
• Has pregnancy or breastfeeding.
• Has any medical or psychiatric condition that, in the investigator's judgment, would interfere with study participation or interpretation of results.