Nephroureterectomy With and Without Lymph Node Dissection for Upper Tract Urothelial Cell Carcinoma

Randomized-Controlled Trial Examining Oncologic and Perioperative Outcomes for Nephroureterectomy With and Without Lymph Node Dissection for Upper Tract Urothelial Cell Carcinoma

The goal of this study is to conduct the first randomized-controlled trial to determine the oncologic efficacy of lymph node dissection in participants with upper tract urothelial cell carcinoma. The main questions it aims to answer are:

• To determine oncologic outcomes, specifically 2-year recurrence-free survival
• To determine other oncologic outcomes including treatment-free, cancer-specific and overall survival
• To determine time to recurrence and recurrence patterns
• To determine use of adjuvant therapies
• To determine perioperative complications

Participants will undergo nephroureterectomy with or without lymph node dissection. Researchers will compare these two groups to determine the oncologic efficacy of performing lymph node dissection.

Study Overview

• Status: Recruiting
• Conditions: Urothelial Carcinoma
• Intervention / Treatment: Procedure: Nephroureterectomy; Procedure: Lymph Node Dissection

Detailed Description

Upper Tract Urothelial Carcinoma (UTUC) is a rare disease with complex management. Some participants with clinically negative nodes may still receive a lymph node dissection (LND) with nephroureterectomy, and currently, no randomized controlled trial exists to evaluate the oncologic efficacy of this practice. According to current American Urologic Association guidelines, Nephroureterectomy is the standard of care intervention for high-risk UTUC and low-risk UTUC is endoscopically unresectable. The aim of the present study is to determine the efficacy, specifically 2-year recurrence-free survival, of lymph node dissection at time of nephroureterectomy for participants with UTUC, compared to no lymph node dissection, as well as examine other oncologic outcomes and complication rates

• Study Type: Interventional
• Enrollment (Estimated): 94
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Mohamed Eltemamy, MD; Phone Number: 216-444-5888; Email: Eltemam@ccf.org
• Study Contact Backup: Name: Rebecca Campbell, MD; Phone Number: 216-444-1105; Email: CAMPBER7@ccf.org

Study Locations

• United States
  • Florida
    • Gainesville, Florida, United States, 32209
      • Recruiting
      • University of Florida Health Science Center
      • Contact: Tarik Benidir, MD
      • Sub-Investigator: Tarik Benidir, MD
  • Illinois
    • Springfield, Illinois, United States, 62702
      • Recruiting
      • Southern Illinois University
      • Contact: Mohammad Mahmoud, MD; Email: mmahmoud96@siumed.edu
      • Principal Investigator: Mohammad Mahmoud, MD
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Recruiting
      • Cleveland Clinic Glickman Urological and Kidney Institute
      • Contact: Mohamed Eltemamy, MD; Phone Number: 216-444-5888; Email: Eltemam@ccf.org
    • Cleveland, Ohio, United States, 44106
      • Recruiting
      • University Hospitals Cleveland Medical Center, Urology Institute, Case Comprehensive Cancer Center
      • Contact: Adam Calaway, MD, MPH; Email: Adam.Calaway@UHhospitals.org
      • Principal Investigator: Adam Calaway, MD, MPH

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Adults > 18 years
• Diagnosis of UTUC as determined by upper tract biopsy (either low or high grade)
• Planned for nephroureterectomy by their urologic surgeon
• Disease that is ≤cT4, N0M0. Participants must have complete TNM staging prior to surgery. cT disease can be determined by biopsy of the mass (if biopsy was deep enough) or imaging (CT/MRI). cN and cM stage must be determined by preoperative imaging of the chest, abdomen and pelvis.
• No concomitant muscle-invasive bladder cancer
• Subjects must have the ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

• Pathologically enlarged lymph nodes suspicious for metastases which would require lymph node dissection regardless of trial (>cN0)
• Presence of distant metastases
• Concomitant muscle invasive bladder cancer
• The participant is in a reduced general condition or has a life-threatening disease.
• The participant has a psychiatric disorder that precludes them from understanding the consent process.
• The patient is pregnant

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Nephroureterectomy With Lymph Node Dissection; Participants will undergo nephroureterectomy for UTUC and will receive LND.	Procedure: Nephroureterectomy; Participants will undergo standard-of-care nephroureterectomy for UTUC.; Procedure: Lymph Node Dissection; Participants will receive lymph node dissection alongside nephroureterectomy for UTUC.
Active Comparator: Nephroureterectomy Without Lymph Node Dissection; Participants will undergo nephroureterectomy for UTUC and will not receive LND.	Procedure: Nephroureterectomy; Participants will undergo standard-of-care nephroureterectomy for UTUC.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recurrence-free survival	Kaplan-Meier will compare recurrence-free survival time between participants who received LND vs participants who did not receive LND.	2 years post-op

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment-free survival	Kaplan-Meier will compare treatment-free survival time between participants who received LND vs participants who did not receive LND.	2 years post-op
Cancer-specific survival	Kaplan-Meier will compare cancer-specific survival time between participants who received LND vs participants who did not receive LND.	2 years post-op
Overall Survival	Kaplan-Meier will compare the overall survival between participants who received LND vs participants who did not receive LND.	2 years post-op
Time to recurrence	Kaplan-Meier will compare the time to disease recurrence between participants who received LND vs participants who did not receive LND.	2 years post-op
Use of adjuvant therapies	T-test or the Wilcoxon rank-sum test will be applied to determine the rate of adjuvant therapies used between participants who received LND vs participants who did not receive LND.	2 years post-op
Perioperative complications	T-test or the Wilcoxon rank-sum test will be applied to determine the rate of perioperative complications between participants who received LND vs participants who did not receive LND.	2 years post-op

Collaborators and Investigators

• Sponsor: Case Comprehensive Cancer Center
• Investigators: Principal Investigator: Mohamed Eltemamy, MD, Cleveland Clinic, Glickman Urological and Kidney Institute, Case Comprehensive Cancer Center; Principal Investigator: Adam Calaway, MD, MPH, University Hospitals Cleveland Medical Center, Urology Institute, Case Comprehensive Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): May 17, 2024
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2029

Study Registration Dates

• First Submitted: February 6, 2024
• First Submitted That Met QC Criteria: February 8, 2024
• First Posted (Actual): February 16, 2024

Study Record Updates

• Last Update Posted (Estimated): September 5, 2025
• Last Update Submitted That Met QC Criteria: September 3, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: Nephroureterectomy; Kidney and ureter; Upper Tract Urothelial Cell Carcinoma
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Carcinoma; Carcinoma, Transitional Cell; Surgical Procedures, Operative; Urologic Surgical Procedures; Urogenital Surgical Procedures; Nephrectomy; Lymph Node Excision; Nephroureterectomy
• Other Study ID Numbers: CASE2824

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: This will be shared via a redcap database. All of the variables listed in the PRMC protocol and IRB application will be shared.
• IPD Sharing Time Frame: From when the trial starts (receives IRB approval and recruitment is initiated) until 1 year after the final participant finishes 2 year follow-up.
• IPD Sharing Access Criteria: This will be shared with the following people at UH PI, research coordinator, residents/fellows/other attendings who are included on the IRB at UH.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No