Eingeschränkte vs Ausgedehnte Lymphadenektomie LEA

Study Overview
=================
Brief Summary
-----------------
This trial evaluates the therapeutic benefit of extended versus limited lymphadenectomy at the time of radical cystectomy in patients with bladder cancer.

Detailed Description
-----------------
The extent of pelvic lymphadenectomy in the surgical treatment of muscle-invasive, clinically locally bladder cancer is not yet standardized. There are no data from randomized, prospective studies on the prognostic role of regional lymphadenectomy. Results of retrospective studies suggest, that the prognosis of patients with muscle-invasive bladder cancer can be improved by extending the limits of pelvic lymphadenectomy. Furthermore it could be demonstrated in a prospective study that the pattern of metastasis of bladder cancer has a high variability. About two-thirds of lymph node metastases are found outside the normally cleared areas of lymphadenectomy. In this study patients will be randomized into arms with limited versus extended lymphadenectomy. The limited lymphadenectomy includes the removal of the obturatoric, external and internal iliac lymph nodes, the extended one includes the removal of all lymph nodes between pelvic floor and the inferior mesenteric artery. The primary objective of the study is to detemine the influence of limited versus extended lyphadenectomy at the time of radical cystectomy on recurrence-free survival. Secondary study objectives include the influence on cancer-specific survival, overall survival, complication rates, histopathologic N-stage, the localization of recurrence and influence of adjuvant chemotherapy . Adjuvant chemotherapy is optional and is recommended in patients with locally advanced disease (pT3/4) or regional lymph node metastasis (pN+).

Official Title
-----------------
Prospektiv Randomisierte Studie Zum Vergleich Einer Ausgedehnten Mit Einer eingeschränkten Pelvinen Lymphadenektomie Bei Der Operativen Therapie Des Harnblasenkarzinoms

Conditions
-----------------
Bladder Cancer

Intervention / Treatment
-----------------
* Procedure: limited lymphadenectomy
* Procedure: extended lymphadenectomy


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Histologically proven, invasive urothelial bladder cancer, locally completely resectable (T1G3 - T4a, Nx) Age >= 18 years Written consent of the patient Patient compliance and geographic proximity to allow adequate follow-up Exclusion Criteria: Histologically or by imaging diagnostics proven organ metastases Radiographic evidence of enlarged lymph nodes (> 1 cm) above the aortic bifurcation in conjunction with pelvic lymph node metastases Radiographic or other evidence of T4b-tumor (infiltration of the pelvic wall or other organ systems) Prior neoadjuvant chemotherapy of bladder cancer Prior previous pelvic lymphadenectomy Prior radiotherapy to the pelvis internal medical or anesthetic risk factors that require a short operation time Palliative cystectomy (f.e. bulky-disease, infiltration of adjacent structures) Evidence of another tumor restricting life expectancy of the patient

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: limited lymphadenectomy<br>Fields 5, 7, 9, 11, 13, 14 are removed | Procedure: limited lymphadenectomy<br>* Field 5 (Group external iliac rigt) Field 7 (Group external iliac left) Field 9 (obturatorical Group right) Field 11 (obturatorical Group left) Field 13 (Group internal iliac right) Field 14 (Group internal iliac left)<br>* Other names: eingeschränkte LA;|
| Experimental: extended lymphadenectomy<br>Fields 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 are removed | Procedure: extended lymphadenectomy<br>* Field 1 (paracaval right) Field 2 (interaortocaval) Field 3 (paraaortal left) Field 4 (Group iliac artery right) Field 5 (Group external iliac rigt) Field 6 (Group iliac artery left) Field 7 (Group external iliac left) Field 8 (presacral) Field 9 (obturatorical Group right) Field 10 (deep obturatorical Group right) Field 11 (obturatorical Group left) Field 12 (deep obturatorical Group left) Field 13 (Group internal iliac right) Field 14 (Group internal iliac left)<br>* Other names: ausgedehnte LA;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recurrence free Survival (RFS) | Definition Recurrence-free survival: Time from radical cystectomy to tumor reccurence or death from any cause up to 5 years | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cancer specific survival (CSS) | Definition Cancer-specific suvival: Time from radical cystectomy to death from bladder cancer up to 5 years | 5 years | 
| Overall survival (OS) | Definition Overall survival: Time from radical cystectomy to death from any cause up to 5 years | 5 years | 
| Determination of type and location of tumour progression(local recurrences and distant metastases) |  | 5 years | 
| Effect on histopathological stage (Will Rogers phenomenon) | Definition Effect on histopathologic stage: Influence of extended lymphadenectomy on detection of lymph node metastasis | 5 years | 
| Influence of adjuvant chemotherapy (by subgroup analysis) |  | 5 years | 
| Documentation of complications |  | 5 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Lymphadenectomy, Extension, Bladder cancer