Template Lymph Node Dissection for Tumor Control in High-Risk Renal Cell Carcinoma: A Prospective, Open-Label, Multicenter, Randomized Controlled Trial
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 220
- 试验地点
- 1
- 主要终点
- Incidence and Severity of Postoperative Complications (Perioperative Safety)
研究概览
简要总结
The goal of this clinical trial is to learn if a more thorough lymph node removal surgery, called "Template Lymph Node Dissection," can help prevent cancer from returning and help patients live longer, compared to removing only a few enlarged lymph nodes, in patients with high-risk kidney cancer. The main questions it aims to answer are:
Do patients who receive template lymph node dissection live longer without their cancer returning (Disease-Free Survival)? Do patients who receive template lymph node dissection live longer overall (Overall Survival)? Is the more extensive lymph node surgery as safe as the limited surgery? Researchers will compare the Template Lymph Node Dissection group to the Limited Node Resection group to see the effects on cancer control and safety.
Participants will:
Be randomly assigned to one of the two surgical groups. Undergo surgery to remove their kidney and the assigned lymph nodes. Attend regular follow-up visits with imaging scans (like CT or MRI) for the first 5 years after surgery to monitor if the cancer returns.
Be followed for their overall survival status for up to 10 years.
详细描述
Research Background:
Renal cell carcinoma (RCC) remains a significant urological malignancy with rising global incidence. Radical nephrectomy (RN) is the standard curative treatment for localized disease. The therapeutic value of lymph node dissection (LND) in RCC, however, remains controversial. The EORTC 30881 trial demonstrated no survival benefit for RN with LND in clinically node-negative (cN0) patients, leading to its omission in contemporary guidelines. However, this trial predominantly included low-risk patients with a low incidence of pathological nodal involvement (4.0%), rendering it underpowered to evaluate LND efficacy in high-risk populations. Conversely, robust retrospective evidence suggests that in patients with high-risk features-such as advanced T-stage, large tumor size, sarcomatoid differentiation, or venous thrombus-more extensive LND may confer a therapeutic benefit by eradicating micrometastatic disease and improving cancer-specific survival. The advent of effective adjuvant immunotherapy (e.g., pembrolizumab) further underscores the need for accurate nodal staging and re-evaluation of LND's role. This prospective, randomized controlled trial aims to definitively assess the oncological benefit and safety of template-based LND in a rigorously selected high-risk RCC cohort.
Research Objectives:
Primary Objectives:
To compare the impact of RN combined with template lymph node dissection versus RN alone on overall survival (OS) and disease-free survival (DFS) in patients with high-risk RCC.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 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
- •Signed informed consent form.
- •Age > 18 years.
- •Candidate for radical nephrectomy with or without lymph node dissection.
- •High-risk renal cell carcinoma defined as: At least ONE of: Clinical stage cT3-4 N0-1 M0 (AJCC 8th ed); OR radiologically visible lymph node >1cm; OR M1 disease rendered no evidence of disease (NED) after local therapy; OR radiologically determined rT4 stage. OR at least TWO of: Renal vein or inferior vena cava tumor thrombus; OR nuclear grade 3-4 or sarcomatoid differentiation or coagulative necrosis; OR tumor size >= 10cm; OR hematuria and/or local symptoms.
- •Measurable disease as per RECIST v1.
- •ECOG performance status of 0 or
- •Adequate bone marrow, renal, and hepatic function.
- •For women and men of childbearing potential, agreement to use effective contraception during the study period.
排除标准
- •Prior radiotherapy, chemotherapy, major surgery, or targeted therapy for RCC.
- •Concurrent other active malignancy (except controlled malignancies not affecting 2-year survival).
- •Candidate for partial nephrectomy or ablation per multidisciplinary team assessment.
- •Preoperative imaging indicates unresectable regional lymph nodes.
- •renal tumors or known hereditary RCC syndrome.
- •Diagnosis of any other active malignancy within the past 5 years.
- •Active autoimmune disease or history of autoimmune disease.
- •Use of immunosuppressive agents within 2 weeks prior to enrollment.
- •Poorly controlled cardiac or clinical symptoms.
- •Coagulopathy or bleeding tendency.
- •Active gastrointestinal conditions with risk of bleeding or perforation.
- •History of significant bleeding or thromboembolic events within specified timeframes.
- •Active infection or unexplained fever >38.5°C.
- •Abdominal fistula, gastrointestinal perforation, or abscess within 4 weeks prior.
- •History of pulmonary fibrosis, interstitial lung disease, or severely impaired pulmonary function.
- •Known immunodeficiency or active hepatitis.
- •Participation in another clinical trial within 1 month.
- •Known history of drug abuse or alcohol addiction.
- •Inability or unwillingness to bear the self-paid portion of examination and treatment costs.
- •Any condition that, in the investigator's judgment, may compromise patient safety or study conduct.
研究组 & 干预措施
Template Lymph Node Dissection
Patients randomized to this arm will undergo radical nephrectomy (which may be performed via open, laparoscopic, or robot-assisted approach based on the surgeon's expertise) combined with a standardized template lymph node dissection.
The template lymph node dissection is defined as follows:
For Left-sided Tumors: Removal of lymphatic tissue anterior and lateral to the abdominal aorta, extending from the diaphragmatic crus superiorly to the aortic bifurcation inferiorly, including the renal hilar lymph tissue.
For Right-sided Tumors: Removal of lymphatic tissue surrounding the inferior vena cava and in the interaortocaval space, extending from the liver edge of the vena cava superiorly to the iliac vein bifurcation inferiorly, including the renal hilar lymph tissue.
干预措施: Template Lymph Node Dissection (Procedure)
Selective Lymph Node Resection
Patients randomized to this arm will undergo radical nephrectomy (which may be performed via open, laparoscopic, or robot-assisted approach). In this arm, only lymph nodes that are identified as >1 cm in the short axis on preoperative cross-sectional imaging (CT/MRI) OR are grossly enlarged and suspicious during the surgeon's intraoperative assessment will be resected. If no such nodes are identified preoperatively or intraoperatively, no formal lymph node dissection is performed.
干预措施: Selective Lymph Node Resection (Procedure)
结局指标
主要结局
Incidence and Severity of Postoperative Complications (Perioperative Safety)
时间窗: From the date of surgery until 30 days post-operation.
A composite measure to assess the safety of the surgical procedures, including: 1. Incidence and severity of postoperative complications graded by Clavien-Dindo classification. 2. Operative time (minutes). 3. Estimated intraoperative blood loss (milliliters). 4. Length of postoperative hospital stay (days).
Disease-Free Survival (DFS)
时间窗: From randomization until the first occurrence of disease recurrence, second primary cancer, or death from any cause, assessed up to 10 years.
Time from randomization to the first documented disease recurrence (local, regional, or distant metastasis), occurrence of a second primary renal cell carcinoma, or death from any cause, whichever occurs first.
Overall Survival (OS)
时间窗: From randomization until death from any cause, assessed up to 10 years.
Time from randomization to death from any cause.
Perioperative Safety
时间窗: From the date of surgery until 30 days post-operation.
A composite measure to assess the safety of the surgical procedures, including: 1. Incidence and severity of postoperative complications graded by Clavien-Dindo classification. 2. Operative time (minutes). 3. Estimated intraoperative blood loss (milliliters). 4. Length of postoperative hospital stay (days).
次要结局
- Absolute Number of Retrieved Lymph Nodes per Anatomic Template(Assessed on the surgical pathology report, immediately after surgery (within approximately 4 weeks post-operation).)
- Pathological Nodal Positivity Rate (pN+%) per Anatomic Template(Assessed on the surgical pathology report, immediately after surgery (within approximately 4 weeks post-operation).)
- Cancer-Specific Survival (CSS)(From randomization until death from kidney cancer, assessed up to 10 years.)
- Anatomic Lymph Node Mapping and Metastasis Rate(Assessed on the surgical pathology report, immediately after surgery (within approximately 4 weeks post-operation).)
- Predictive Nomogram for Lymph Node Metastasis(Model development and internal validation will be performed after complete recruitment and surgical pathology data are available for all participants, estimated to be 3 years after study start.)
- Exploration of Biomarkers for Survival(Biomarker analysis will be conducted after sufficient clinical outcome data (DFS/OS events) are available, estimated to be 5 years after study start.)