The Prognostic Role of Lymph Node Dissection In Men With Prostate Cancer Treated With Radical Prostatectomy

Study Overview
=================
Brief Summary
-----------------
An extended pelvic lymph node dissection (ePLND) is the most accurate staging method to assess the presence of lymph node metastases in prostate cancer (PCa) patients. The therapeutic value, however remains unclear. Prospective randomized trials to address this void are lacking. Since in intermediate and a proportion of high risk PCa the risk of nodal metastases is generally below 25%, the vast majority of men undergo a procedure that has no oncological benefit, but is not without toxicity. Therefore, the investigators aim to compare the oncologic outcomes of intermediate- and high-risk PCa patients with an estimated risk of lymph node invasion of 5-20% undergoing a radical prostatectomy (RP) with or without an ePLND.

Detailed Description
-----------------
The role of an extended pelvic lymph node dissection (ePLND) in patients undergoing radical prostatectomy (RP) remains controversial. An ePLND is the most accurate staging method to assess the presence of lymph node metastases. Lymph node involvement is associated with a significantly worse prognosis and may require immediate or delayed adjuvant therapy. However, an ePLND is associated with an increased risk of complications such as lymphoceles, thromboses and lymphedema, and prolongs surgery and patient recovery. Thus, the diagnostic advantage of PLND should be weighed against the potential morbidity. The therapeutic value of an ePLND remains especially unclear in PCa patients with an estimated risk of lymph node invasion (LNI) ≤ 20%, where only a minority of patients will have nodes harbouring metastases. Prospective trials to address this issue are still lacking.

Official Title
-----------------
Prospective Randomized Controlled Trial To Evaluate The Prognostic Role of Lymph Node Dissection In Men With Prostate Cancer Treated With Radical Prostatectomy

Conditions
-----------------
Prostate Cancer

Intervention / Treatment
-----------------
* Procedure: Pelvic lymph node dissection


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male, aged ≥ 18 years Prostate cancer patients with a Briganti calculated risk of LN metastases of 5-20% without evidence of metastases on Prostate-Specific Membrane Antigen (PSMA) PET/CT requiring an ePLND in the standard treatment Scheduled for a (robot-assisted) laparoscopic radical prostatectomy Written informed consent Exclusion Criteria: American Society of Anaesthesiology (ASA) classification > 3 Patients with a contradiction for a lymphadenectomy Neoadjuvant hormone deprivation therapy Absence or withdrawal of an informed consent Evidence of metastases on pre-operative PSMA PET/CT

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

Sexes Eligible for Study
-----------------
Male

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 |
| --- | --- |
| Active Comparator: Radical prostatectomy with an extended pelvic lymph node dissection<br>According to the standard of care, patients in this arm will receive a radical prostatectomy with a standard bilateral ePLND. This includes the removal of lymph nodes within the obturator fossa and bilateral to the external iliac artery, internal iliac artery and common iliac artery up to the ureteral-vessel crossing. | Procedure: Pelvic lymph node dissection<br>* Bilateral extended pelvic lymph node dissection<br>|
| No Intervention: Radical prostatectomy without an extended pelvic lymph node dissection<br>Patients in this arm will undergo a radical prostatectomy without a bilateral extended pelvic lymph node dissection. In case of intraoperatively found suspicious lymph nodes, a lymphadenectomy is performed. According to the intention to treat principle, patients with intraoperatively removed lymph nodes remain included in the study. | |

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Persistent PSA rate | Persistent PSA is defined as a PSA value ≥ 0.1 ng/ml after radical prostatectomy | 6 months after surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Biochemical recurrence (BCR) rate | BCR is defined as a PSA value ≥ 0.2 ng/ml after radical prostatectomy | 3 years after surgery | 
| Metastasis-free survival | This is defined as the time between radical prostatectomy to development of metastasis | 3 years after surgery | 
| Incidence of complications after surgery | According to Clavien-Dindo classification | 3 and 6 months after surgery | 
| Incidence of salvage therapy after primary surgery | I.e., androgen deprivation therapy, radiation therapy or salvage lymph node dissection | 3 years after surgery | 
| Global Quality of life after surgery | Quality of life (QoL) will be assessed with the EORTC Core Quality of Life questionnaire's (QLQ-C30) global QoL scale ranging from 0 to 100, higher scores indicate better QoL | 6, 12, 24 and 36 months after surgery | 
| Health-related quality of life of patients with prostate cancer | Health-related quality of life in prostate cancer patients will be assessed with the EORTC Quality of Life Questionnaire - Prostate Cancer Module (QLQ-PR25) with a scale ranging from 0 to 100, higher scores indicate either more symptoms (urinary, bowel, hormonal treatment-related symptoms) or higher levels of (sexual) activity or functioning | 6, 12, 24 and 36 months after surgery | 
| Urinary continence after surgery | Urinary continence will be assessed with the International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF) questionnaire, ranging from 0 (best) to 21 (worst) | 6, 12, 24 and 36 months after surgery | 
| Urinary voiding symptoms | Urinary voiding symptoms will be assessed with the International Prostatic Symptoms Score (IPSS), ranging from 0 (best) to 35 (worst) | 6, 12, 24 and 36 months after surgery | 
| Potency after surgery | Potency will be assessed with the International Index of Erectile Function (IIEF) questionnaire. The IIEF classifies the severity of erectile dysfunction into five categories stratified by score: No erectile dysfunction. Score: 26-30 Mild erectile dysfunction. Score: 22-25 Mild to moderate erectile dysfunction. Score: 17-21 Moderate erectile dysfunction. Score: 11-16 Severe erectile dysfunction. Score: 6-10. | 6, 12, 24 and 36 months after surgery | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Prostate Cancer, Lymph node dissection, Prostatectomy