Lymphadenectomy in Urothelial Carcinoma

Sponsor
Zealand University Hospital (Other)
Overall Status
Recruiting
CT.gov ID
NCT02607709
Collaborator
(none)
366
1
2
187
2

Study Details

Study Description

Brief Summary

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.

Condition or Disease Intervention/Treatment Phase
  • Procedure: Lymphadenectomy in conjugation with nephroureterectomy
  • Procedure: Nephroureterectomy without lymphadenectomy
N/A

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 Design

Study Type:
Interventional
Anticipated Enrollment :
366 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Lymphadenectomy in Urothelial Carcinoma in the Renal Pelvis and Ureter
Actual Study Start Date :
Jun 1, 2016
Anticipated Primary Completion Date :
Jan 1, 2022
Anticipated Study Completion Date :
Jan 1, 2032

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures

  1. Recurrence free survival [Five years]

Secondary Outcome Measures

  1. Incidence of metastasis [Five years]

Other Outcome Measures

  1. Complications [Within 30 days after operations]

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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

Contacts and Locations

Locations

Site City State Country Postal Code
1 Roskilde Hospital Roskilde Denmark 4000

Sponsors and Collaborators

  • Zealand University Hospital

Investigators

  • Study Chair: Nessn H Azawi, MB.Ch.B., Roskilde University Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

Responsible Party:
Nessn Azawi, Urologist, Zealand University Hospital
ClinicalTrials.gov Identifier:
NCT02607709
Other Study ID Numbers:
  • REG-79-2015
First Posted:
Nov 18, 2015
Last Update Posted:
Sep 20, 2021
Last Verified:
Sep 1, 2021
Additional relevant MeSH terms:

Study Results

No Results Posted as of Sep 20, 2021