Emulated-target Trial for Guiding Stratified Treatment for Renal Cell Carcinoma With Venous Tumor Thrombus
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 4,700
- 试验地点
- 1
- 主要终点
- Disease-free Survival
研究概览
简要总结
This single-center study utilizes real-world data (2012-2024) from 4700 renal cell carcinoma (RCC) patients at Peking University Third Hospital to: (1) Develop and validate a prognostic prediction model specifically for RCC patients, including those with venous tumor thrombus (VTT); (2) Compare the performance of this new model against existing RCC prediction models in both the overall RCC cohort and the VTT subgroup; (3) Employ an emulated target trial (ETT) methodology to evaluate whether risk-stratified treatment based on the prediction model (grouping patients as high/medium/low risk) improves survival outcomes .
详细描述
- Study Design and Technical Approach:
This is a single-center, observational study utilizing real-world data (RWD) to achieve three primary objectives within a renal cell carcinoma (RCC) cohort, specifically focusing on patients with venous tumor thrombus (VTT):
- Objective 1 (Model Comparison): Compare the performance (discrimination, calibration, stability) of the newly developed prediction model against existing published RCC prediction models within the overall cohort and the VTT subgroup.
- Objective 2 (Causal Evaluation via ETT): Employ an Emulated Target Trial (ETT) framework to evaluate the causal impact of risk-stratified treatment guided by the prediction model on survival and health economic outcomes, compared to non-stratified treatment.
- Study Population and Data Source:
- Source: Peking University Third Hospital, Urology Department.
- Cohort: A bidirectional cohort comprising:
- Retrospective component: ~4000 RCC patients treated between January 2012 and June 2025.
- Prospective component: All eligible RCC patients treated between Dec 2025 and Dec 2026 (target total N=4700, including ~446 VTT patients).
- Inclusion Criteria: (1) Age 18-80 years; (2) Clinical diagnosis of RCC; (3) Underwent radical/partial nephrectomy.
- Exclusion Criteria: (1) Severe missing clinical information; (2) Distant metastasis at baseline; (3) History of other malignancies.
- Data Collection: Comprehensive candidate variables include demographics, lab results, imaging, treatment details (surgery, systemic therapy - neoadjuvant/adjuvant), pathology (including VTT level), and follow-up data.
- Core Methodologies:
- Missing Data: Assessed for patterns. Addressed primarily via Multiple Imputation. Sensitivity analyses will evaluate the impact of missing data assumptions.
- Outliers: Identified through data review; verified against source; excluded if confirmed erroneous.
- Emulated Target Trial (ETT):
- Objective: Estimate the effect of adhering to risk-stratified treatment (based on the model's High/Intermediate/Low risk groups) versus non-adherence.
- "Treatment" Definition: SHAP analysis will identify key features defining risk groups and inform optimal treatment strategies per group. Adherence is determined by comparing actual treatment received to the predicted risk group's recommended strategy (e.g., type/extent of surgery, use of neoadjuvant/adjuvant systemic therapy/radiotherapy).
- Group Assignment: Non-random, based on actual treatment:
- Intervention Group (Adherent): Patients whose received treatment aligned with their predicted risk stratum.
- Control Group (Non-Adherent): Patients whose received treatment did not align with their predicted risk stratum.
- Baseline: Defined as the time of first meeting eligibility criteria (also considered treatment assignment time for ETT).
- Causal Inference & Confounding Control: Uses cloning-censoring-weighting methods to emulate randomization. Directed Acyclic Graphs (DAGs) will identify key confounders for adjustment. Intention-To-Treat (ITT) principle is the primary analysis; Per-Protocol (PP) is secondary.
- Follow-up: Starts at baseline. Includes telephone and outpatient visits. Frequency based on EAU RCC guidelines by risk group. Continues until outcome (death, recurrence), withdrawal, or study end. Captures survival, recurrence, QoL, resource utilization/costs.
- Outcomes:
- Primary: Overall Survival (OS).
- Secondary: Model performance.
- Statistical Analysis Plan:
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Other
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adults ≥18 years of age;
- •Diagnosis of primary renal cell carcinoma before and during the surgery;
- •Received radical nephrectomy/nephron-sparing surgery.
排除标准
- •Subjects with severely missing clinical information;
- •History of other malignant tumors.
- •Recurrence observed before first postoperative follow-up.
- •Discontinue the adjuvant treatment within in the first two course because of severe adverse react.
研究组 & 干预措施
model-stratified group
Patient receiving treatment in accord with stratified result of the established model.
干预措施: Model-guided adjuvant treatment (Procedure)
non-model-stratified group
Patient receiving treatment not in accord with stratified result of the established model.
干预措施: No adjuvant treatment (Procedure)
结局指标
主要结局
Disease-free Survival
时间窗: From date of follow-up until the date of (1) local or regional recurrence, (2) distant recurrence, (3) second primary cancer, or (4) death from any cause., whichever came first, assessing up to 48 months.
The duration from the date of diagnosis to death or last follow-up, with no restriction on the cause of death.
次要结局
未报告次要终点