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:

  1. No visible bladder tumor on cystoscopy;
  2. Negative bladder biopsy and/or TURBT pathology;
  3. Negative urine cytology;
  4. Negative urinary tumor DNA (utDNA);
  5. 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.