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NCT Number: NCT07475403

Urinary Tumor DNA-Guided Systemic Immunotherapy for 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.

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Key information

Conditions

Bladder Cancer Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Immunotherapy Liquid Biopsy Male Urogenital Diseases Neoplasms Neoplasms by Site Urinary Bladder Diseases Urinary Bladder Neoplasms Urogenital Diseases Urogenital Neoplasms Urologic Diseases Urologic Neoplasms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

The Second Hospital of Tianjin Medical University, Tianjin, China

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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.

Exclusion criteria

  • Muscle-invasive bladder cancer (≥T2), locally advanced unresectable invasive disease beyond NMIBC, or metastatic urothelial carcinoma at baseline.
  • 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.
  • Prior treatment with immune.
  • Active autoimmune disease or history of autoimmune disease requiring systemic immunosuppressive treatment and considered incompatible with immune checkpoint inhibitor therapy.
  • Ongoing systemic immunosuppressive therapy exceeding protocol-allowed doses.
  • Active uncontrolled infection, including uncontrolled urinary tract infection, that would interfere with study treatment or response assessment.
  • Any medical condition that would preclude safe administration of systemic immunotherapy or protocol-required cystoscopy/TURBT/biopsy, in the investigator's judgment.
  • Concurrent other malignancy. 10. Pregnant or breastfeeding women. 11. Inability to comply with protocol procedures or follow-up.

Treatment and study plan

Systemic immunotherapy

Drug

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

Primary outcomes

  1. Event-Free Survival

    Time frame: Up to 2 years first administration of systemic immunotherapy

    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.

Secondary outcomes

  1. Duration of Complete Response

    Time frame: Up to 2 years from first documented complete clinical 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.

  2. Radical Cystectomy-Free Survival

    Time frame: Up to 2 years from first administration of systemic immunotherapy

    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.

  3. Overall Survival

    Time frame: Up to 2 years from first administration of systemic immunotherapy

    Overall survival is defined as the time from the first administration of systemic immunotherapy to death from any cause.

  4. Number of Participants With Treatment Emergent Adverse Events (TEAEs)

    Time frame: From first administration of systemic immunotherapy up to 30 days after last administration of study

    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.

Other outcomes

  1. EORTC QLQ-C30

    Time frame: Up to 2 years from first administration of systemic immunotherapy

    To assess disease-related symptoms and HRQoL

  2. EORTC QLQ-NMIBC24

    Time frame: Up to 2 years from first administration of systemic immunotherapy

    To assess disease-related symptomd and HRQoL

  3. EQ-5L

    Time frame: Up to 2 vears from first administration of systemic immunotherapy

    To assess disease-related symptoms and HRQoL

Study contacts

Contact information is provided by the study sponsor or research team.

Hailong Hu

CONTACT

[email protected]

+8619801518556

Sponsors and collaborators

Lead sponsor

Tianjin Medical University Second Hospital

Other

Registry information

Official study title

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

Important dates

Study start
2026
Primary completion
2028
Study completion
2029
First posted
Mar 16, 2026
Registry last updated
May 26, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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