A Prospective Study of Urinary Tumor DNA-Guided Systemic Immunotherapy in Patients With Unresectable Very-High-Risk Non-Muscle-Invasive Bladder Cancer
This study aims to evaluate whether urinary tumor DNA (utDNA) can guide treatment duration in patients with unresectable very-high-risk non-muscle-invasive bladder cancer (VHR NMIBC) who achieve complete clinical response after systemic immunotherapy. Participants will receive systemic immunotherapy followed by response assessment using pathology, cystoscopy, urine cytology, and utDNA testing. Patients who achieve complete clinical response will receive a short additional course of immunotherapy before stopping treatment according to the study protocol. The study hypothesizes that a shortened duration of systemic immunotherapy guided by utDNA monitoring may maintain favorable oncologic outcomes in this population.
• Age ≥18 years.
• Histologically confirmed non-muscle-invasive urothelial carcinoma of the bladder classified as very-high-risk (VHR) according to EAU 2025 guideline criteria.
• Disease considered unresectable by the investigator and multidisciplinary team, defined as complete tumor eradication by standard transurethral resection of bladder tumor (TURBT) being not feasible or unlikely to achieve adequate local control.
• Patients who are ineligible or refuse for radical cystectomy, after discussion with the treating team.
• At least one measurable or evaluable bladder lesion/documented residual disease suitable for response assessment by cystoscopy, TURBT/biopsy, pathology, urine cytology, and urinary tumor DNA (utDNA) testing.
• ECOG performance status 0-2.
• Adequate organ function, including:
• Hematologic function: Absolute neutrophil count ≥1.5 × 10⁹/L, Platelet count ≥100 × 10⁹/L, Hemoglobin ≥9 g/dL Hepatic function: Total bilirubin ≤1.5 × ULN, AST ≤2.5 × ULN, ALT ≤2.5 × ULN Renal function: Serum creatinine ≤1.5 × ULN or Creatinine clearance ≥60 mL/min.
• Ability to provide urine samples for utDNA testing and urine cytology during treatment and follow-up.