Circulating and Urine Tumor DNA Dynamics Predict Minimal Residual Disease and Recurrence Risk in Locally Advanced Upper Tract Urothelial Carcinoma(CURATE-UTUC): A Multicenter Prospective Longitudinal Cohort Study
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 84
- 试验地点
- 1
- 主要终点
- extravesical recurrence free survival
研究概览
简要总结
In our study, the ultra-deep sequencing of circulating tumor DNA (ctDNA) and urine tumor DNA (utDNA) were performed to assess whether ctDNA and utDNA can be used as predictive biomarkers for the detection of minimal residual disease (MRD) and early diagnosis of UTUC recurrence, and explored the role of ctDNA and utDNA detection of MRD in the prediction of adjuvant therapy efficacy and prognostic evaluation.
详细描述
60% of Upper Urinary Tract Urothelial Carcinoma (UTUC) patients with muscle-invasive disease at diagnosis, which progresses rapidly, aggressively, and has a poor prognosis. Up to 30-40% of the patients may develop bladder recurrance after radical nephroureterectomy for primary upper tract urothelial carcinoma.
Minimal residual disease (MRD) refers to the small number of malignant cells that remain after curative treatments (curative intent surgical resection, radiotherapy, and/or chemotherapy). MRD is common in patients with blood cancer, and is known to be associated with recurrence and poor prognosis. Recent studies also reported that MRD-negative in postoperative solid tumors such as colorectal/colon cancer and muscle-invasive bladder cancer is associated with better survival outcomes. However, the clinical values of MRD monitoring for adjuvant therapy in postoperative UTUC remain inadequate.
A total of 84 patients with stage II-IV UTUC will be recruited in this clinical trial. The following plasma samples, urine samples and tumor tissues will be collected from each patient including T0 (preoperatively, 2[1-3] days before surgery), T1 (28±3 days postoperatively), T2 (within 7 days after cycle 2 adjuvant therapy), T3 (end-of-treatment), and quarterly/semi-annually during surveillance (T4-T6) until recurrence/24 months. In addition, demographic and tumor characteristics of the patients will be collected for subsequent analysis, including age, sex, tumor stage, pathological stage, disease couse time, etc. Tumor tissues and matched peripheral blood were collected before treatment and WES was used ctDNA detection techniques. For each patient, we selected up to 40 clonal somatic mutations for personalized, tumor informed ctDNA assay design.Statistical analyses will be performed to analyze the survival outcomes and to explore the clinical value of MRD monitoring for adjuvant therapy in postoperative UTUC.
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
- •pathological comfirmed T2-4 or N+ and M0 upper tract urothelial carcinoma
- •Male or female aged ≥18 years old who are willing to sign the informed consent form
- •have no distant metastasis
- •have an ECOG 0 to 2
- •upper tract urothelial carcinoma patients received radical nephroureterectomy
- •have no multiple primary carcinoma
- •received adjuvant chemotherapy or immunotherapy after surgery within 12 weeks
- •≥2 postoperative liquid biopsy assessments (T1 and T2)
排除标准
- •a prior history of bladder or synchronous bladder cancer
- •Pregnant or lactating women, or patients who are fertile but do not take contraceptive measures;
- •Severe infection;
- •Severe heart disease;
- •Uncontrollable neurological or mental disorders;
- •Severe diabetes mellitus;
- •Patients with severe autoimmune diseases.
- •Neoadjuvant therapy exposure
- •No bilateral UTUC
- •Surveillance time < month
- •<2 postoperative MRD surveillance assessments
研究组 & 干预措施
adjuvant chemotherapy group
muscle invasive upper tract urothelial carcinoma after radical nephroureterectomy receiving adjuvant chemotherapy
干预措施: Adjuvant chemotherapy (Drug)
adjuvant immunotherapy group
muscle invasive upper tract urothelial carcinoma after radical nephroureterectomy receiving adjuvant immunotherapy
干预措施: adjuvant immunotherapy (Drug)
结局指标
主要结局
extravesical recurrence free survival
时间窗: 2 year
The primary endpoint was extravesical recurrence-free survival (eRFS), defined as the time from radical nephroureterectomy (RNU) to the first occurrence of either locoregional recurrence (e.g., retroperitoneal lymph node, local soft tissue) or distant metastasis, as objectively confirmed by radiological imaging (CT or MRI) according to RECIST 1.1 criteria. Death from any cause without a prior documented extravesical recurrence was considered a competing risk event.
次要结局
- Lead time of molecular recurrence detection(2 year)
- intravesical recurrence free survival(2 year)
- recurrence-free survival(2 year)
- Overall survival(2 year)
- Diagnostic performance of MRD assay(2 year)