Urinary Tumor DNA-Guided Systemic Immunotherapy for Unresectable Very-High-Risk Non-Muscle-Invasive Bladder Cancer

Официальное название

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

Обзор

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.

Вмешательства

• Препарат 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 re

Первичные конечные точки

• Event-Free Survival [Срок оценки: Up to 2 years first administration of systemic immunotherapy]

Вторичные конечные точки (4)

• Duration of Complete Response [Срок оценки: Up to 2 years from first documented complete clinical response]
• Radical Cystectomy-Free Survival [Срок оценки: Up to 2 years from first administration of systemic immunotherapy]
• Overall Survival [Срок оценки: Up to 2 years from first administration of systemic immunotherapy]
• Number of Participants With Treatment Emergent Adverse Events (TEAEs) [Срок оценки: From first administration of systemic immunotherapy up to 30 days after last administration of study]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 3 центра

• The Second Hospital of Tianjin Medical University — Тяньцзинь
• Tianjin Hospital — Тяньцзинь
• Xingtai People's Hospital — Xingtai

Идентификаторы

NCT: NCT07475403 · Truce-LB03B

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗