Internal Validation of Circulating Tumor DNA (ctDNA) Sequencing in Muscle-Invasive Bladder Cancer and Upper Tract Urothelial Carcinoma: A Prospective Observational Study
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 70
- 试验地点
- 1
- 主要终点
- Diagnostic Performance of Plasma ctDNA for Detecting Tumor-Specific Mutations
研究概览
简要总结
This prospective observational study evaluates a blood-based circulating tumor DNA (ctDNA) test in patients with muscle-invasive bladder cancer or upper tract urothelial cancer. ctDNA consists of small fragments of tumor DNA that can sometimes be detected in the blood.
In this study, DNA from tumor tissue obtained during routine diagnostic or surgical procedures will be analyzed to identify tumor-specific mutations. Blood samples collected during routine clinical care will then be tested to determine whether the same mutations can be detected in plasma ctDNA.
The main purpose is to assess how well the internally developed ctDNA assay detects tumor-specific mutations compared with tumor tissue sequencing. The study will also explore whether ctDNA results after treatment are associated with recurrence or remission during two years of follow-up, and whether changes in ctDNA levels during treatment are associated with pathological response.
This study does not assign participants to a treatment and does not require additional blood draws beyond routine care. Treating physicians will remain blinded to ctDNA results during the study, so the test results will not influence clinical decisions.
详细描述
Muscle-invasive bladder cancer and muscle-invasive upper tract urothelial carcinoma are associated with a relevant risk of recurrence or progression after treatment. Current follow-up mainly relies on imaging, pathology, and clinical assessment. Circulating tumor DNA (ctDNA) may provide additional information on tumor burden, minimal residual disease, and treatment response, but clinical implementation remains limited by cost, logistics, and the need for local assay validation.
This study evaluates an internally developed, tumor-informed ctDNA workflow in patients treated at AZ Sint-Lucas Gent. Tumor DNA will be extracted from available formalin-fixed paraffin-embedded tumor tissue, such as tissue obtained during transurethral resection of bladder tumor, upper tract biopsy, nephro-ureterectomy, cystectomy, or biopsy of metastatic disease. Targeted next-generation sequencing will be used to identify patient-specific somatic mutations in the tumor tissue.
When tumor-specific mutations are identified, matched plasma samples collected during routine clinical care will be analyzed for the same mutations. Cell-free DNA will be extracted from plasma and ctDNA detection will be performed using a tumor-informed approach, primarily by digital droplet PCR for known tumor-specific mutations. Mutations that cannot be assessed by digital droplet PCR may be further evaluated using next-generation sequencing.
Blood samples will be obtained only as part of routine diagnostic, staging, treatment, or follow-up blood draws. The study does not assign participants to a specific treatment and does not require additional study-specific therapeutic interventions. Patients will receive standard clinical care according to institutional practice.
Treating physicians will remain blinded to the ctDNA results during the study. The ctDNA results are investigational and will not guide treatment decisions during the study period. Clinical, pathological, treatment, molecular, and follow-up data will be collected to assess the performance of the assay and to explore associations between ctDNA status, treatment response, recurrence, progression, and remission over two years of follow-up.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
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 or older.
- •Histologically confirmed muscle-invasive bladder cancer or suspected muscle-invasive upper tract urothelial carcinoma, stage T2 or higher.
- •Availability of tumor tissue from transurethral resection of bladder tumor, ureteroscopic biopsy, biopsy of a metastatic lesion, or nephroureterectomy for DNA extraction.
- •Written informed consent provided.
排除标准
- •- Concurrent active malignancy diagnosed within the past 5 years.
结局指标
主要结局
Diagnostic Performance of Plasma ctDNA for Detecting Tumor-Specific Mutations
时间窗: From enrollment until completion of tumor tissue sequencing and matched plasma ctDNA analysis, up to 6 months
Concordance between tumor-specific somatic mutations identified in tumor tissue and the same mutations detected in matched plasma-derived ctDNA. Diagnostic performance of the internally developed ctDNA assay will be assessed using sensitivity, specificity, positive predictive value, and negative predictive value, with tumor tissue sequencing as the reference standard.
次要结局
- Association Between Post-Treatment ctDNA Positivity and Disease Recurrence or Progression(Up to 2 years after surgery or radiotherapy)
- Association Between Post-Treatment ctDNA Negativity and Disease Remission(Up to 2 years after surgery or radiotherapy)
- Association Between Preoperative ctDNA Negativity and Pathological T0 Status(At cystectomy)
- Association Between Quantitative ctDNA Decrease During Neoadjuvant Therapy and Pathological Downstaging(From start of neoadjuvant therapy until cystectomy, up to 6 months)
- Time Difference Between ctDNA Rise and Imaging-Detected Disease Relapse(Up to 2 years after curative treatment)