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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Prostate Cancer
• Intervention / Treatment: Procedure: Pelvic lymph node dissection

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.

• Study Type: Interventional
• Enrollment (Anticipated): 284
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Henk G van der Poel, Prof; Phone Number: 0205129111; Email: h.vd.poel@nki.nl
• Study Contact Backup: Name: Hilda A de Barros, MD; Phone Number: 0205129111; Email: h.d.barros@nki.nl

Study Locations

• Netherlands
  • Amsterdam, Netherlands, 1066 CX
    • Recruiting
    • NKI-AvL
    • Contact: H.G van der Poel, Prof

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Radical prostatectomy with an extended pelvic lymph node dissection; 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; Bilateral extended pelvic lymph node dissection
NO_INTERVENTION: Radical prostatectomy without an extended pelvic lymph node dissection; 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

Collaborators and Investigators

• Sponsor: The Netherlands Cancer Institute
• Investigators: Principal Investigator: Henk G van der Poel, Prof, the Netherlands Cancer Institute

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): November 17, 2021
• Primary Completion (ANTICIPATED): November 1, 2024
• Study Completion (ANTICIPATED): November 1, 2027

Study Registration Dates

• First Submitted: August 26, 2021
• First Submitted That Met QC Criteria: October 25, 2021
• First Posted (ACTUAL): November 5, 2021

Study Record Updates

• Last Update Posted (ACTUAL): November 18, 2021
• Last Update Submitted That Met QC Criteria: November 17, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: Prostate Cancer; Prostatectomy; Lymph node dissection
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms
• Other Study ID Numbers: M20PRD

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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