Using urinary tumor DNA to guide how long systemic immunotherapy is given for unresectable very‑high‑risk non‑muscle‑invasive bladder cancer.

A Prospective Study of Urinary Tumor DNA-Guided Systemic Immunotherapy in Patients With Unresectable Very-High-Risk Non-Muscle-Invasive Bladder Cancer

This trial will test whether monitoring urinary tumor DNA lets people with unresectable very‑high‑risk non‑muscle‑invasive bladder cancer stop systemic immunotherapy sooner after they have a complete clinical response.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 53 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Tianjin Medical University Second Hospital (Academic / other)
• Drugs / interventions: immunotherapy
• Locations: 1 site (Tianjin)
• Trial ID: NCT07475403 on ClinicalTrials.gov

What this trial studies

In this Phase 2 interventional trial, participants with unresectable very‑high‑risk non‑muscle‑invasive bladder cancer receive systemic immunotherapy and undergo response checks using cystoscopy, biopsy/pathology, urine cytology, and urinary tumor DNA (utDNA) testing. Patients who achieve a complete clinical response receive a short additional course of immunotherapy and then stop treatment according to the protocol while utDNA is used to guide timing. Oncologic outcomes and recurrence will be monitored clinically and with molecular testing. The study aims to see if utDNA-guided shortening of systemic immunotherapy can preserve cancer control while reducing treatment exposure.

Who should consider this trial

Good fit: Adults (≥18) with histologically confirmed very‑high‑risk non‑muscle‑invasive bladder cancer judged unresectable, who are ineligible for or refuse radical cystectomy, have at least one evaluable bladder lesion, ECOG 0–2, and adequate organ function are ideal candidates.

Not a fit: Patients who are suitable for curative radical cystectomy, have muscle‑invasive disease, lack detectable utDNA, or who do not achieve a complete clinical response are unlikely to benefit from a shortened immunotherapy strategy.

Why it matters

Potential benefit: If successful, this approach could let patients stop systemic immunotherapy earlier, reducing side effects, time on treatment, and costs while maintaining cancer control.

How similar studies have performed: Urine tumor DNA and other liquid biopsy methods have shown promise for monitoring bladder cancer, but using utDNA to guide shortening of systemic immunotherapy is a novel strategy that is not yet validated in large trials.

Eligibility criteria

Inclusion Criteria:

1. Age ≥18 years.
2. Histologically confirmed non-muscle-invasive urothelial carcinoma of the bladder classified as very-high-risk (VHR) according to EAU 2025 guideline criteria.
3. 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.
4. Patients who are ineligible or refuse for radical cystectomy, after discussion with the treating team.
5. 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.
6. ECOG performance status 0-2.
7. 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.
8. Ability to provide urine samples for utDNA testing and urine cytology during treatment and follow-up.

Exclusion Criteria:

1. Muscle-invasive bladder cancer (≥T2), locally advanced unresectable invasive disease beyond NMIBC, or metastatic urothelial carcinoma at baseline.
2. Histology showing predominant or pure non-urothelial carcinoma of the bladder that, in the investigator's judgment, would make the patient unsuitable for this protocol.
3. Prior treatment with immune.
4. Active autoimmune disease or history of autoimmune disease requiring systemic immunosuppressive treatment and considered incompatible with immune checkpoint inhibitor therapy.
5. Ongoing systemic immunosuppressive therapy exceeding protocol-allowed doses.

7\. Active uncontrolled infection, including uncontrolled urinary tract infection, that would interfere with study treatment or response assessment.

8\. Any medical condition that would preclude safe administration of systemic immunotherapy or protocol-required cystoscopy/TURBT/biopsy, in the investigator's judgment.

9\. Concurrent other malignancy. 10. Pregnant or breastfeeding women. 11. Inability to comply with protocol procedures or follow-up.

Where this trial is running

Tianjin

• The Second Hospital of Tianjin Medical University — Tianjin, China (Recruiting)

Study contacts

• Study coordinator: Hailong Hu

Conditions Bladder Cancer; Liquid Biopsy; Immunotherapy