A Prospective Study of Urinary Tumor DNA-Guided Systemic Immunotherapy in Patients With Unresectable Very-High-Risk Non-Muscle-Invasive Bladder Cancer
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 53
- 试验地点
- 3
- 主要终点
- Event-Free Survival
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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-
- •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.
排除标准
- •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.
- •Pregnant or breastfeeding women.
- •Inability to comply with protocol procedures or follow-up.
研究组 & 干预措施
Study group
干预措施: Systemic immunotherapy (Drug)
结局指标
主要结局
Event-Free Survival
时间窗: 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.
次要结局
- Radical Cystectomy-Free Survival(Up to 2 years from first administration of systemic immunotherapy)
- Overall Survival(Up to 2 years from first administration of systemic immunotherapy)
- Duration of Complete Response(Up to 2 years from first documented complete clinical response)