NCT07321210

Radical Nephroureterectomy With vs Without Template Lymph Node Dissection in High-Risk Upper Tract Urothelial Carcinoma (T-LND UTUC): A Randomized Clinical Trial

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

• Status: Recruiting
• Phase: N/A
• Study type: Interventional
• Enrollment: 150 (estimated)
• Sponsor: Tianjin Medical University Second Hospital · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

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： 1. Primary Objectives: 1. 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. 2. 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. 2. Secondary Objectives: 1. To compare non-urothelial tract recurrence-free survival (NU-RFS), intravesical recurrence-free survival (IFS), and cancer-specific survival (CSS) between the two groups. 2. To establish a lymph node metastasis (pN+) mapping profile for different UTUC tumor locations using template-based LND. 3. Exploratory Objectives: 1. To identify molecular biomarkers predictive of prognosis using bulk RNA sequencing of prospectively collected tumor tissues. 2. To develop a lymph node metastasis prediction nomogram based on radiomic data from contrast-enhanced CT, tumor characteristics, lymph node size/location, and clinical symptoms. Methods： This is a prospective, multicenter, open-label, randomized controlled trial. A total of 150 eligible patients with high-risk UTUC (cT2-4N0-1M0 or cT1N1M0) will be randomized in a 1:1 ratio to one of two arms: Experimental Arm (A): RNU + template LND Control Arm (B): RNU + removal of only radiologically or intraoperatively detected lymph nodes \>1 cm Stratified randomization will be performed based on tumor location (renal pelvis/upper ureter, mid-ureter, lower ureter) and clinical nodal status (cN0 vs. cN1). Surgical approach (open, laparoscopic, or robotic) will be at the surgeon's discretion, but LND must adhere to predefined anatomical templates. Patients will be followed for up to 10 years, with regular imaging, urine cytology, and cystoscopy according to a standardized schedule. DFS, OS, and other survival endpoints will be analyzed using Kaplan-Meier methods and Cox proportional hazards models. Safety will be assessed via Clavien-Dindo grading and monitoring of adverse events. Innovation： This trial addresses a critical evidence gap in UTUC management by providing the first high-level, prospective, randomized data on the therapeutic efficacy of template LND. Key innovative aspects include: 1. Standardization of LND templates based on tumor location, enhancing surgical consistency and pathological staging. 2. Incorporation of biomarker and radiomic analyses to explore predictive signatures for lymph node involvement and survival. 3. A multicenter design ensuring generalizability and sufficient power to detect clinically meaningful differences in survival outcomes. 4. Potential to establish LND as a standard of care for high-risk UTUC, thereby informing future guidelines and improving oncologic outcomes.

Conditions

• Upper Tract Urothelial Carcinoma
• Lymph Node Dissection

Interventions

Type	Name	Description
PROCEDURE	Template Lymph Node Dissection	A systematic and anatomic-based lymph node dissection performed during radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC). The dissection boundaries are strictly defined by a pre-specified template according to 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 goal is potential therapeutic benefit by removing nodal metastatic disease.
PROCEDURE	Selective Lymph Node Resection	A diagnostic procedure performed during radical nephroureterectomy (RNU). It does not involve a systematic template dissection. The surgeon will only remove intraoperatively identified suspicious and radiographic lymphadenopathy (\>1 cm in the short-axis diameter). The primary goal is pathological staging rather than therapeutic clearance of a nodal basin.

Timeline

• Start date: 2026-01-01
• Primary completion: 2027-08-30
• Completion: 2032-08-30
• First posted: 2026-01-06
• Last updated: 2026-01-06

Locations

1 site across 1 country: China