Urinary Tumor DNA-Guided Systemic Immunotherapy 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 study evaluates whether urinary tumor DNA (utDNA) testing, together with clinical, pathologic, and radiographic assessment, can help guide treatment discontinuation and active surveillance in patients with unresectable very-high-risk non-muscle-invasive bladder cancer (VHR NMIBC) treated with bladder-sparing systemic immunotherapy.

Participants receive systemic immune checkpoint inhibitor-based therapy every 3 weeks for an initial 3 cycles. Initial response assessment is performed using transurethral resection of bladder tumor (TURBT) and chest and abdominopelvic computed tomography (CT). Participants without progression to muscle-invasive, regional nodal, or distant metastatic disease then undergo post-TURBT urine cytology and urinary tumor DNA (utDNA) testing. Participants with both negative urine cytology and negative utDNA results receive an additional 3 cycles of systemic immunotherapy.

After the additional treatment, participants undergo repeat evaluation using cystoscopy with biopsy, urine cytology, utDNA testing, and chest and abdominopelvic CT. Participants with negative findings on cystoscopic biopsy, urine cytology, and utDNA testing, and without radiographic evidence of nodal or distant metastatic disease, discontinue systemic immunotherapy and enter an active surveillance phase with regular follow-up monitoring. Participants who do not meet these criteria continue further clinical management and follow-up according to institutional practice.

The study aims to determine whether a shortened duration of systemic immunotherapy guided by integrated molecular, clinical, pathologic, and radiographic response assessment can maintain favorable oncologic outcomes while reducing unnecessary treatment exposure in this high-risk population.

Study Overview

• Status: Recruiting
• Conditions: Bladder Cancer; Liquid Biopsy; Immunotherapy
• Intervention / Treatment: Drug: Systemic immunotherapy

• Study Type: Interventional
• Enrollment (Estimated): 53
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Hailong Hu; Phone Number: +8619801518556; Email: huhailong@tmu.edu.cn

Study Locations

• China
  • Tianjin, China, 300000
    • Recruiting
    • The Second Hospital of Tianjin Medical University
    • Contact: Hailong Hu; Phone Number: +8615620530409; Email: xzh200049@163.com
  • Tianjin, China
    • Recruiting
    • Tianjin Hospital
    • Contact: Guangbin Zhu; Phone Number: +8613662096232; Email: zgb111@163.com
  • Xingtai, China
    • Recruiting
    • Xingtai People's Hospital
    • Contact: Junli Wei; Phone Number: +8615620530409; Email: wjlmnwk@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Study group

Drug: Systemic immunotherapy; Participants receive systemic immune checkpoint inhibitor-based therapy administered intravenously every 3 weeks for an initial 3 cycles. Treatment response is initially assessed using transurethral resection of bladder tumor (TURBT) to evaluate pathologic stage. Participants without progression to muscle-invasive or metastatic disease subsequently undergo post-TURBT urine cytology and urinary tumor DNA (utDNA) testing. Participants with both negative urine cytology and negative utDNA results receive an additional 3 cycles of systemic immunotherapy. Following the additional treatment, participants undergo repeat evaluation using cystoscopy with biopsy, urine cytology, and utDNA testing. Participants with negative findings on cystoscopic biopsy, urine cytology, and utDNA testing discontinue systemic immunotherapy and enter an active surveillance phase with regular follow-up monitoring. Participants who do not meet these criteria continue further clinical management and follow-up accord

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Event-Free Survival	Event-free survival is defined as the time from initiation of systemic immunotherapy to the first occurrence of any of the following events after entry into the active surveillance phase: histologically confirmed intravesical recurrence of urothelial carcinoma, progression to muscle-invasive bladder cancer (≥T2 disease), regional lymph node or distant metastasis identified on chest or abdominopelvic computed tomography (CT), radical cystectomy, or death from any cause.. Residual non-muscle-invasive bladder cancer identified during the initial TURBT-based response assessment is not considered an event. Isolated urinary tumor DNA (utDNA) positivity without pathologically confirmed disease recurrence or progression is not considered an event.	Up to 2 years first administration of systemic immunotherapy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Radical Cystectomy-Free Survival	Radical cystectomy-free survival is defined as the time from the first administration of systemic immunotherapy to the first occurrence of either radical cystectomy or death from any cause.	Up to 2 years from first administration of systemic immunotherapy
Overall Survival	Overall survival is defined as the time from the first administration of systemic immunotherapy to death from any cause.	Up to 2 years from first administration of systemic immunotherapy
Duration of Complete Response	Duration of complete response is defined, among participants who achieve confirmed complete clinical response (cCR) at repeat evaluation after additional systemic immunotherapy, as the time from the first documentation of confirmed cCR to the first occurrence of any of the following events: histologically confirmed intravesical recurrence of urothelial carcinoma, progression to muscle-invasive bladder cancer (≥T2 disease), regional lymph node or distant metastasis identified on imaging evaluation, radical cystectomy, or death from any cause. Confirmed complete clinical response is defined as negative findings on cystoscopy with biopsy, negative urine cytology, negative urinary tumor DNA (utDNA), and absence of muscle-invasive, nodal, or metastatic disease on chest and abdominopelvic computed tomography (CT). Isolated urinary tumor DNA (utDNA) positivity without pathologically confirmed disease recurrence or radiographically confirmed progression is not considered an event.	Up to 2 years from first documented complete clinical response
Number of Participants With Treatment Emergent Adverse Events (TEAEs)	An adverse event (AE) was any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. TEAEs were those events with onset dates occurring during the on-treatment period. On-treatment period was defined as the time from the first dose of study treatment up to 30 days after last dose of study treatment or 1 day before start day of new anti-cancer therapy.	From first administration of systemic immunotherapy up to 30 days after last administration of study

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
EORTC QLQ-C30	To assess disease-related symptoms and HRQoL	Up to 2 years from first administration of systemic immunotherapy
EORTC QLQ-NMIBC24	To assess disease-related symptomd and HRQoL	Up to 2 years from first administration of systemic immunotherapy
EQ-5L	To assess disease-related symptoms and HRQoL	Up to 2 vears from first administration of systemic immunotherapy

Collaborators and Investigators

• Sponsor: Tianjin Medical University Second Hospital

Study record dates

Study Major Dates

• Study Start (Actual): March 16, 2026
• Primary Completion (Estimated): April 1, 2028
• Study Completion (Estimated): April 1, 2029

Study Registration Dates

• First Submitted: March 11, 2026
• First Submitted That Met QC Criteria: March 11, 2026
• First Posted (Actual): March 16, 2026

Study Record Updates

• Last Update Posted (Actual): May 26, 2026
• Last Update Submitted That Met QC Criteria: May 21, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Male Urogenital Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urologic Neoplasms; Urinary Bladder Diseases; Urinary Bladder Neoplasms
• Other Study ID Numbers: Truce-LB03B

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: At this stage, a decision regarding sharing individual participant data (IPD) has not been finalized. The study involves sensitive clinical and genomic information, including urinary tumor DNA (utDNA) data, and careful consideration is required to ensure protection of participant privacy and compliance with applicable ethical and regulatory requirements. Data sharing policies will be determined after study completion, taking into account institutional policies, participant consent, and data protection regulations. Requests for data may be considered on a case-by-case basis.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No