Radical Nephrectomy With vs Without Template Lymph Node Dissection in High-Risk Renal Cell Carcinoma (T-LND RCC): A Randomized Clinical Trial (RECLND)

December 21, 2025 updated by: Tianjin Medical University Second Hospital

Template Lymph Node Dissection for Tumor Control in High-Risk Renal Cell Carcinoma: A Prospective, Open-Label, Multicenter, Randomized Controlled Trial

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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

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.

To evaluate and compare the surgical safety profiles of both approaches, including perioperative complications (graded by Clavien-Dindo classification), operative time, intraoperative blood loss, and length of hospital stay.

Secondary Objectives:

To compare cancer-specific survival (CSS) between the two groups. To quantify the number of lymph nodes retrieved and the incidence of nodal metastases within predefined anatomical templates (renal hilum, para-aortic, paracaval, and interaortocaval regions).

Exploratory Objectives:

To identify molecular biomarkers predictive of nodal metastasis or prognosis using Bulk-RNA sequencing of prospectively collected tumor and blood samples.

To develop a predictive nomogram for lymph node metastasis integrating radiomic features from triple-phase abdominal CT, MRI, tumor characteristics, and clinical symptoms.

Study Methodology:

This is a prospective, open-label, multicenter, randomized controlled trial. A total of 220 eligible patients with high-risk RCC-defined as cT3-4N0-1M0 or M1 disease rendered no evidence of disease (NED) after local therapy-will be randomized in a 1:1 ratio.

Intervention Group (Arm A): Patients will undergo RN plus template LND. The template for left-sided tumors includes lymph nodes from the diaphragmatic crus to the aortic bifurcation (anterior and lateral to the aorta), including the renal hilar nodes. For right-sided tumors, the template extends from the hepatic edge of the inferior vena cava (IVC) to the iliac bifurcation, encompassing paracaval, precaval, and interaortocaval nodes, including the renal hilum.

Control Group (Arm B): Patients will undergo RN with resection only of radiologically or intraoperatively detected lymph nodes ≥1 cm.

Randomization will be centralized and stratified by clinical nodal status (cN0 vs. cN1), prior metastatic status (M0 vs. M1→NED), and participating center. Surgical approach (open, laparoscopic, or robot-assisted) will be at the surgeon's discretion. Postoperative adjuvant therapy with toripalimab (an anti-PD-1 agent) may be offered per patient preference, with one cycle provided free of charge by the study.

Endpoints and Statistical Analysis:

Primary endpoints are DFS and OS. Secondary endpoints include CSS, nodal yield and metastatic rate, and safety. DFS is defined as the time from randomization to recurrence, second primary RCC, or death from any cause. OS is defined as time from randomization to death from any cause. Time-to-event endpoints will be analyzed using Kaplan-Meier methods and compared with the log-rank test. Cox proportional hazards models will be used for multivariable analysis. Categorical variables will be compared using chi-square tests, and continuous variables with t-tests. A sample size of 220 provides 90% power to detect a 21.5% absolute improvement in 5-year OS (76% vs. 54.5%) at a two-sided α of 0.05, accounting for a 10% dropout rate.

Innovation:

This study addresses a critical evidence gap by prospectively evaluating template LND in a meticulously defined high-risk RCC population, including those with M1 NED status-a subgroup with particularly poor prognosis. It employs a standardized, anatomically defined "template" LND to ensure surgical quality and consistency across multiple centers. Furthermore, the study integrates contemporary biomarker and radiomic analyses to explore predictive tools for nodal metastasis and prognosis, which could personalize future surgical and adjuvant strategies. By conducting this trial in the era of adjuvant immunotherapy, it will elucidate whether LND provides independent therapeutic benefit beyond its staging role.

Study Type

Interventional

Enrollment (Estimated)

220

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

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 v1.1. ECOG performance status of 0 or 1. Adequate bone marrow, renal, and hepatic function. For women and men of childbearing potential, agreement to use effective contraception during the study period.

Exclusion Criteria:

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. Bilateral 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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.
Procedure: Template Lymph Node Dissection
A standardized surgical procedure to remove lymph nodes within defined anatomical boundaries during radical nephrectomy for kidney cancer. For left-sided tumors, this includes tissue anterior and lateral to the aorta from the diaphragmatic crus to the aortic bifurcation. For right-sided tumors, it includes tissue around the vena cava and between the vena cava and aorta from the liver edge to the iliac bifurcation. The renal hilar lymph tissue is always included.
Active Comparator: 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.
Procedure: Selective Lymph Node Resection
A surgical approach during radical nephrectomy for kidney cancer where lymph nodes are removed only if they meet specific criteria: being larger than 1 cm on preoperative CT/MRI scans, or appearing grossly enlarged and suspicious to the surgeon during the operation. If no such nodes are identified, no lymph node dissection is performed.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Disease-Free Survival (DFS)
Time Frame: 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.
From randomization until the first occurrence of disease recurrence, second primary cancer, or death from any cause, assessed up to 10 years.
Overall Survival (OS)
Time Frame: From randomization until death from any cause, assessed up to 10 years.
Time from randomization to death from any cause.
From randomization until death from any cause, assessed up to 10 years.
Perioperative Safety
Time Frame: 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).
From the date of surgery until 30 days post-operation.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Cancer-Specific Survival (CSS)
Time Frame: From randomization until death from kidney cancer, assessed up to 10 years.
Time from randomization to death attributable to renal cell carcinoma. Deaths from other causes are censored.
From randomization until death from kidney cancer, assessed up to 10 years.
Anatomic Lymph Node Mapping and Metastasis Rate
Time Frame: Assessed on the surgical pathology report, immediately after surgery (within approximately 4 weeks post-operation).
The absolute number and the pathological nodal positivity rate (pN+%) of lymph nodes retrieved from each of the following predefined anatomical template regions: right renal hilum, suprarenal para-caval, infrarenal para-caval, left renal hilum, suprarenal para-aortic, and renal hilar para-aortic. This assesses the distribution and frequency of lymph node metastasis.
Assessed on the surgical pathology report, immediately after surgery (within approximately 4 weeks post-operation).
Exploration of Biomarkers for Survival
Time Frame: Biomarker analysis will be conducted after sufficient clinical outcome data (DFS/OS events) are available, estimated to be 5 years after study start.
Identification of molecular biomarkers predictive of Disease-Free Survival (DFS), Cancer-Specific Survival (CSS), and Overall Survival (OS) through Bulk-RNA sequencing analysis performed on prospectively collected tumor tissue samples.
Biomarker analysis will be conducted after sufficient clinical outcome data (DFS/OS events) are available, estimated to be 5 years after study start.
Predictive Nomogram for Lymph Node Metastasis
Time Frame: 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.
Development and validation of a predictive nomogram (statistical model) for preoperative estimation of lymph node metastasis risk. The model will integrate radiomic features from contrast-enhanced abdominal CT and non-contrast MRI, along with clinical variables (tumor size/location, retroperitoneal/renal hilar lymph node size/location, and clinical symptoms).
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.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Tianjin Medical University Second Hospital

Collaborators

Sun Yat-sen University
Tianjin Medical University Cancer Institute and Hospital
Tianjin Third Central Hospital
Cancer Hospital Chinese Academy of Medical Science, Shenzhen Center

Investigators

  • Principal Investigator: Changyi Quan, MD, Tianjin Medical University Second Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

January 1, 2026

Primary Completion (Estimated)

September 30, 2028

Study Completion (Estimated)

September 30, 2033

Study Registration Dates

First Submitted

December 21, 2025

First Submitted That Met QC Criteria

December 21, 2025

First Posted (Actual)

January 6, 2026

Study Record Updates

Last Update Posted (Actual)

January 6, 2026

Last Update Submitted That Met QC Criteria

December 21, 2025

Last Verified

December 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • TLND-RCC

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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