Clinical Efficacy and Safety of Radical Nephroureterectomy With Versus Without Template Lymph Node Dissection in High-Risk Upper Tract Urothelial Carcinoma: A Multicenter, Prospective, Randomized Controlled Clinical Trial
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 150
- 试验地点
- 1
- 主要终点
- Disease-Free Survival (DFS)
研究概览
简要总结
The goal of this clinical trial is to learn if adding a template lymph node dissection (TLND) to the standard surgery for upper tract urothelial cancer (UTUC) can improve patient survival and prevent the cancer from recurrence. The main questions it aims to answer are:
Do patients who receive standard surgery with LND live longer without their cancer returning? Is adding LND safe, and how does it affect surgery-related complications? Researchers will compare the group receiving standard surgery plus LND to the group receiving standard surgery alone to see if adding LND is more effective.
Participants will:
Be randomly assigned to one of the two surgical groups. Undergo their assigned surgery and recover in the hospital. Attend regular follow-up visits for checkups and scans for 5 years to monitor for cancer recurrence, with the possibility of long-term follow-up extending to 10 years.
详细描述
Background： Upper tract urothelial carcinoma (UTUC), encompassing renal pelvic and ureteral carcinomas, is a relatively rare but aggressive malignancy of the urinary system, accounting for 5-10% of all urothelial cancers. Radical nephroureterectomy (RNU) with bladder cuff excision remains the gold standard for treating non-metastatic UTUC. However, prognosis remains poor, particularly for patients with locally advanced disease, due to high rates of recurrence and metastasis. The role of concurrent lymph node dissection (LND) during RNU is one of the most debated topics in UTUC management. While LND is widely accepted in muscle-invasive bladder cancer for its diagnostic and therapeutic benefits, its utility in UTUC lacks high-level evidence. Current guidelines conditionally recommend LND for high-risk UTUC based largely on retrospective data, leading to significant heterogeneity in clinical practice. This multicenter, prospective, randomized controlled trial aims to definitively establish the clinical value of template-based LND in high-risk UTUC.
Objectives：
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Primary Objectives:
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To compare the impact of RNU plus template LND versus RNU alone on disease-free survival (DFS) and overall survival (OS) in patients with high-risk non-metastatic UTUC.
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To evaluate and compare the safety profiles of both approaches, including perioperative complications (graded by Clavien-Dindo), operative time, intraoperative blood loss, and length of hospital stay.
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Secondary Objectives:
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To compare non-urothelial tract recurrence-free survival (NU-RFS), intravesical recurrence-free survival (IFS), and cancer-specific survival (CSS) between the two groups.
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To establish a lymph node metastasis (pN+) mapping profile for different UTUC tumor locations using template-based LND.
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Exploratory Objectives:
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
- Single (Outcomes Assessor)
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 written informed consent form (ICF).
- •Age > 18 years at the time of ICF signing.
- •Clinical diagnosis of unilateral Upper Tract Urothelial Carcinoma (UTUC) by imaging (enhanced CT or MRI) and/or ureteroscopic biopsy/urinary cytology, and scheduled to undergo Radical Nephroureterectomy (RNU).
- •Clinical assessment indicating that the tumor and regional lymph nodes are completely resectable, with at least one of the following high-risk features:
- •Locally advanced: Preoperative imaging assessed as cT2 stage or higher (i.e., tumor invades muscularis propria or deeper).
- •High-grade: Preoperative ureteroscopic biopsy pathology confirmed as high-grade urothelial carcinoma (or with squamous differentiation/sarcomatoid differentiation).
- •Moderate or severe hydronephrosis: Ipsilateral moderate or severe hydronephrosis due to tumor obstruction.
- •Large tumor size: Imaging measures maximum tumor diameter > 2 cm.
- •cN1: Imaging suggests regional lymph node short-axis diameter > 1 cm, and the investigator judges it to be resectable.
- •Presence of at least one measurable lesion according to RECIST v1.1 criteria.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
- •Adequate organ function meeting the following requirements (without use of any blood components or colony-stimulating factors within 14 days):
- •Bone marrow function: Neutrophils ≥ 1,500/mm³, Platelets ≥ 100,000/mm³, Hemoglobin ≥ 9 g/dL (5.6 mmol/L).
- •Renal function: Serum creatinine ≤ 1.5 mg/dL and/or Creatinine clearance ≥ 60 mL/min.
- •Liver function: Total bilirubin ≤ 1.5 × ULN, AST & ALT ≤ 1.5 × ULN.
- •For women of childbearing potential (WOCBP): Must agree to use a highly effective medically approved contraceptive method during the treatment period and for 3 months after treatment ends. A negative serum or urine pregnancy test within 7 days before enrollment is required; must be non-lactating. For non-sterilized male patients: Must agree to use effective contraception with their partner during the treatment period and for 3 months after treatment ends.
- •Subject voluntarily joins the study, has good compliance, and agrees to undergo safety and survival follow-up.
排除标准
- •Previous receipt of any anti-tumor therapy for UTUC, including chemotherapy, radiotherapy, immunotherapy, or targeted therapy.
- •History or concurrent presence of muscle-invasive bladder urothelial carcinoma.
- •Preoperative imaging assesses regional lymph nodes as unresectable: lymph nodes fused into a massive conglomerate, or fully encasing the abdominal aorta/inferior vena cava/pelvic vessels preventing safe separation.
- •Known bilateral UTUC or hereditary diseases that definitively increase the risk of contralateral upper tract tumors, such as Lynch Syndrome.
- •Diagnosis of other active malignancies within the past 5 years (except for adequately treated basal cell carcinoma, squamous cell carcinoma of the skin, or carcinoma in situ of the cervix which have been cured and show no recurrence within 5 years).
- •Presence of any active autoimmune disease or history of autoimmune disease.
- •Current use of immunosuppressants for immunosuppressive purposes, continued within 2 weeks prior to enrollment.
- •Poorly controlled cardiac clinical symptoms or diseases.
- •Coagulation abnormalities or bleeding tendency.
- •Presence of specific active gastrointestinal conditions or uncontrolled tumor bleeding.
- •History of significant bleeding, hemoptysis, or thromboembolic events within specified timeframes.
- •Active infection or unexplained fever > 38.5°C during screening or before the first dose.
- •Occurrence of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 4 weeks prior to surgery.
- •History or current objective evidence of pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonitis, drug-related pneumonia, severely impaired pulmonary function, etc.
- •Congenital or acquired immunodeficiency.
- •Participation in another clinical study within 1 month prior to enrollment, or potential receipt of other systemic anti-tumor therapy during the study period.
- •Known history of psychotropic drug abuse, alcohol abuse, or drug use.
- •Inability or unwillingness to bear the out-of-pocket costs of examinations and treatments.
- •Any other condition deemed by the investigator to make the subject unsuitable for participation.
研究组 & 干预措施
RNU + Template Lymph Node Dissection
Participants in this arm will undergo Radical Nephroureterectomy (RNU) combined with template Lymph Node Dissection (LND). The LND will be performed according to a predefined template based on the primary tumor location: renal hilum+para-aortic (left hilar and paraaortic) or renal hilum+para-caval (right hilar, paracaval, and interaortocaval) for renal pelvis/upper ureter; extended to common/external iliac for mid-ureter; and pelvic (common, external, internal iliac, and obturator) for lower ureter. The surgical approach (open, laparoscopic, or robot-assisted) is at the surgeon's discretion.
干预措施: Template Lymph Node Dissection (Procedure)
RNU + Selective Lymph Node Resection
Participants in this arm will undergo Radical Nephroureterectomy (RNU) alone. No template lymph node dissection will be performed. However, if intraoperatively identified suspicious and radiographic lymphadenopathy (>1 cm in the short-axis diameter) are present, they may be removed for pathological staging purposes only.
干预措施: Selective Lymph Node Resection (Procedure)
结局指标
主要结局
Disease-Free Survival (DFS)
时间窗: From date of randomization until the date of first documented progression, recurrence, or death from any cause, assessed up to 5 years. (Assessments: every 3 months for the first 2 years, then every 6 months for years 3-5.)
Time from randomization to the first documented occurrence of disease recurrence (local, regional nodal, or distant metastasis), new urothelial carcinoma in the contralateral upper tract or bladder, or death from any cause, whichever occurs first.
Overall Survival (OS)
时间窗: From date of randomization until the date of death from any cause, assessed up to 5 years. (Assessments: every 3 months.)
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: Incidence and severity of postoperative complications graded by Clavien-Dindo classification. Operative time (minutes). Estimated intraoperative blood loss (milliliters). Length of postoperative hospital stay (days).
次要结局
- Non-Urothelial Tract Recurrence-Free Survival (NU-RFS)(From date of randomization until the date of first documented non-urothelial recurrence or death, assessed up to 5 years. (Assessments: every 3 months for the first 2 years, then every 6 months for years 3-5.))
- Intravesical Recurrence-Free Survival (IFS)(From date of randomization until the date of first documented intravesical recurrence or death, assessed up to 5 years. (Assessments: cystoscopy every 6 months for the first 2 years, then as per protocol.))
- Cancer-Specific Survival (CSS)(Time Frame: From date of randomization until the date of death due to urothelial carcinoma, assessed up to 5 years. (Assessments: every 3 months.))
- Lymph Node Metastasis Map(At time of surgery (from final pathological report, approximately 4 weeks post-operation))