Lymphadenectomy in Urothelial Carcinoma

January 27, 2024 updated by: Nessn Azawi, Zealand University Hospital

Lymphadenectomy in Urothelial Carcinoma in the Renal Pelvis and Ureter

Two out of three tumours in the upper urinary tract are located in the renal pelvis. Muscle-invasive urothelial carcinoma is probably more common among tumours in the upper urinary tract compared to tumours in the urinary bladder. Thus, muscle-invasive tumours represent approximately 45 % of renal pelvic tumours compared to 25 % of tumours within the urinary bladder. As in the bladder, lymph node metastases are rare in non-muscle invasive disease. Information regarding indications, extent and possible curative potential is currently lacking for lymphadenectomy in conjunction with nephroureterectomy for urothelial carcinoma in the upper urinary tract (UUTUC). There are, however, retrospective series with survival data for patients with lymph node metastasis that report long term survival after surgery as monotherapy [4] with similar survival proportions as in bladder cancer with lymph node metastases after radical cystectomy. A retrospective study from Tokyo was expanded to the only available prospective study, where 68 patients with UUTUC were submitted to template-based lymphadenectomy. Another retrospective study by the same Japanese group, showed that 5-year cancer-specific and recurrence-free survival was significantly higher in the complete lymphadenectomy group than in the incomplete lymphadenectomy or without lymphadenectomy groups. Tanaka N et al. reported recurrence rate after nephroureterectomy without lymphadenectomy at 1 and 3 years were 18.9 and 29.8 %, respectively.

Study Overview

Status

Suspended

Conditions

Intervention / Treatment

Detailed Description

Background:

Two out of three tumours in the upper urinary tract are located in the renal pelvis. Muscle-invasive urothelial carcinoma is probably more common among tumours in the upper urinary tract compared to tumours in the urinary bladder. Thus, muscle-invasive tumours represent approximately 45 % of renal pelvic tumours compared to 25 % of tumours within the urinary bladder. As in the bladder, lymph node metastases are rare in non-muscle invasive disease. Information regarding indications, extent and possible curative potential is currently lacking for lymphadenectomy in conjunction with nephroureterectomy for urothelial carcinoma in the upper urinary tract (UUTUC). There are, however, retrospective series with survival data for patients with lymph node metastasis that report long term survival after surgery as monotherapy with similar survival proportions as in bladder cancer with lymph node metastases after radical cystectomy. A retrospective study from Tokyo was expanded to the only available prospective study, where 68 patients with UUTUC were submitted to template-based lymphadenectomy. Another retrospective study by the same Japanese group, showed that 5-year cancer-specific and recurrence-free survival was significantly higher in the complete lymphadenectomy group than in the incomplete lymphadenectomy or without lymphadenectomy groups. Tanaka N et al. reported recurrence rate after nephroureterectomy without lymphadenectomy at 1 and 3 years were 18.9 and 29.8 %, respectively.

Hypothesis: Complete lymphadenectomy during nephroureterectomy because of invasive urothelial carcinoma may reduce the incidence of lymph nodes metastasis, local recurrence, distant metastasis and improve the cancer survival rate.

Purpose: To evaluate the influence of complete lymphadenectomy on recurrence and cancer specific survival rate compared to limited or no lymphadenectomy.

Primary endpoint/analysis: Recurrence free survival at five-year postoperative. Secondary endpoints: Incidence of lymph node metastases, local recurrence and/or distant metastasis, cancer specific and overall survival at one, three and five-year postoperative. Complications rate according to Clavien classification within the first thirty days postoperatively.

Another endpoint/analysis: Multivariate analysis of possible preoperative risk factors for lymph node metastases (tumour size, preoperative urinary cytology, lymph node enlargement on CT, PET-CT positivity) and postoperative risk factors for lymph node metastases (stage, grade, tumour diameter, presence of necrosis in the tumour (none; <10%; >10% of total tumour area), number of lymph nodes excised).

Design: Prospectively randomized to template based lymphadenectomy or not, in patients with clinically muscle-invasive UUTUC in the renal pelvis or upper 2/3 of the ureter. One to one, controlled clinical trial. Patients will be randomly allocated into two groups, 183 patients in each group. Group A will be scheduled to receive routine standard open or robot assisted nephroureterectomy without lymphadenectomy except for clinically enlarged. Group B will be scheduled to received mapped lymphadenectomy in conjugation with nephroureterectomy.

Study Type

Interventional

Enrollment (Estimated)

366

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

Study Contact Backup

Study Locations

  • Denmark
      • Roskilde, Denmark, 4000
        • Roskilde Hospital

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

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Age above 18 years
  2. Locally advanced high grade urothelial carcinoma in the renal pelvis or upper 2/3 of the ureter (Clinical stage > T1)
  3. Patient with ECOG performance score of 2 and less.
  4. Able to give informed consent

Exclusion Criteria:

  1. Clinical suspicion of non-muscle invasive UUTUC
  2. Metastatic urothelial carcinoma for the renal pelvis or upper 2/3 of the ureter
  3. Inability to understand written consent forms or give consent

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
Placebo Comparator: Nephroureterektomy
scheduled to receive routine standard open or robot assisted nephroureterectomy without lymphadenectomy
Procedure: Nephroureterectomy without lymphadenectomy
Removing the kidney, ureter and bladder cuff
Experimental: Nephroureterektomy + Lymphadenectomy
scheduled to received mapped lymphadenectomy in conjugation with nephroureterectomy
Procedure: Lymphadenectomy in conjugation with nephroureterectomy

Lymphadenectomy (intervention group only):

Lymphadenectomy performs in four fractions on the right side and two fractions on the left side according to Dissection template (Appendix 1). Renal hilar nodes are included in fraction 1 and 3, respectively.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Recurrence free survival
Time Frame: Five years
Five years

Secondary Outcome Measures

Outcome Measure
Time Frame
Incidence of metastasis
Time Frame: Five years
Five years

Other Outcome Measures

Outcome Measure
Time Frame
Complications
Time Frame: Within 30 days after operations
Within 30 days after operations

Collaborators and Investigators

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

Sponsor

Zealand University Hospital

Investigators

  • Study Chair: Nessn H Azawi, MB.Ch.B., Roskilde University 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 (Actual)

June 1, 2016

Primary Completion (Estimated)

January 1, 2024

Study Completion (Estimated)

January 1, 2024

Study Registration Dates

First Submitted

November 15, 2015

First Submitted That Met QC Criteria

November 17, 2015

First Posted (Estimated)

November 18, 2015

Study Record Updates

Last Update Posted (Actual)

January 30, 2024

Last Update Submitted That Met QC Criteria

January 27, 2024

Last Verified

January 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • REG-79-2015

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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