Clinical trial NCT05000827: Dutch National Randomized Study: PSMA-PET/CT As a Triage Tool for Pelvic Lymph Node Dissection in Prostatectomy Patients
Official title: Multi-institutional Evaluation of the Cost-effectiveness of PSMA-PET/CT for the Detection of Pelvic Lymph Node Invasion in Newly Diagnosed Prostate Cancer Patients
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Prostate Cancer Metastatic
Prostate Cancer
Lymph Node Metastases
Lead sponsor: Canisius-Wilhelmina Hospital
Sponsor class: OTHER
Collaborators: name: ZonMw: The Netherlands Organisation for Health Research and Development
First posted: 2021-08-11
Enrollment: 706
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Intervention

PSMA PET/CT based indication for ePLND:

1. Node-negative PSMA PET/CT \[N0\] and M0: do not perform ePLND
2. Node-positive PSMA PET/CT \[N1\] and M0: perform ePLND

Comparator Nomogram-based indication for ePLND (conform current EAU guidelines)
Primary purpose: DIAGNOSTIC

Brief summary: To determine if the use of Prostate-Specific Membrane Antigen Positron Emission Computer Tomography (PSMA PET/CT) as a selection tool for performing extended lymph node dissection (ePLND) for prostate cancer (PCa) in the primary staging setting results in fewer ePLND procedures and therefore lower overall healthcare costs, lower patient burden in terms of intervention-related complications and morbidity, with comparable disease prognosis, compared to the current European Guideline-recommended standard practice which includes performing ePLND in PCa patients who are candidates for active treatment with a nomogram-calculated lymph node involvement (LNI) risk \>5%.

Detailed description: Background: Use of prostate-specific membrane antigen (PSMA) positron emission tomography (PET) - computer tomography (CT) has drastically improved the ability to detect and exclude presence of pelvic lymph node invasion (LNI) compared to conventional imaging. However, current standard of care still includes performing extended pelvic lymph node dissection (ePLND) in all patients with primary prostate cancer and a nomogram-based risk of LNI \>5%. It is unclear if use of PSMA PET/CT as a triage test can safely reduce the number of ePLND and hence reduce the associated morbidity and costs, without negatively influencing disease prognosis.

Objective: To assess whether PSMA PET/CT can be safely used as a triage test for selecting primary prostate cancer patients for ePLND. We will additionally assess cost-effectiveness of the PSMA PET/ CT triage strategy.

Design, setting and Participants: THE PSMA-SELECT trial includes patients with biopsy-confirmed prostate cancer, without evidence of distant metastasis (M0) on PSMA PET/CT, opting for treatment with radical prostatectomy (RP), with a nomogram-calculated risk of LNI \>5%. Patients will be randomized 1:1. In the intervention arm patients will only undergo ePLND in addition to robot-assisted radical prostatectomy (RARP) in case of suspected LNI on PSMA PET/CT (miN1), whereas ePLND will be omitted in those without PSMA positive lymph nodes (miN0). In the control arm, all patients will undergo ePLND in addition to RARP.

Outcome measurements and statistical analysis: The primary endpoint of this study is biochemical recurrence rate at two years post-surgery. Secondary outcome measures are number of ePLNDs indicated and performed, treatment-related adverse events, initiation of salvage treatment, metastasis-free survival, patient-reported outcome measures and individual and cumulative healthcare costs.

Eligibility criteria: Inclusion Criteria:

* Biopsy proven adenocarcinoma of the prostate
* Indication for ePLND combined with robot assisted radical prostatectomy (RARP) (MSKCC nomogram \>5%, if not applicable when only MRI targeted biopsies are positive, the Briganti nomogram will be used)
* Suitable for robot-assisted ePLND and RARP
* Mentally competent and understanding of benefits and potential burden of the study
* Written informed consent
* No known allergies for PSMA tracer.

Exclusion Criteria:

* History of prior diagnosed or treated PCa
* Known concomitant malignancies (except Basal Cell Carcinoma of the skin)
* Unwillingness or inability to undergo PSMA PET/CT and/or ePLND and RARP
* PSMA non-avid PCa (local tumor activity)
* Presence of distant metastasis (M1)

Primary outcomes:
measure: Difference in biochemical recurrence rate between groups.
timeFrame: 2 years
Secondary outcomes:
measure: Total number of ePLNDs and PSMA PET/CTs performed and their intervention-related healthcare costs
timeFrame: up to 5 years post-surgery
measure: Incidence and types of surgical complications after RARP and ePLND
timeFrame: up to 1 year post-surgery
measure: Total nodes resected on ePLND and number of positive and negative nodes within and outside of the standard ePLND template
timeFrame: up to 5 years post-surgery
measure: Occurrence of pelvic lymph node metastasis and distant metastasis (visceral, bone, distant lymph nodes, pelvic lymph nodes) on PSMA-PET/CT during follow-up
timeFrame: up to 5 years post-surgery
measure: Initiation of salvage therapy
timeFrame: up to 5 years post-surgery
measure: Metastasis-free survival
timeFrame: up to 5 years post-surgery
measure: Hormone-therapy free survival
timeFrame: up to 5 years post-surgery
measure: Diagnostic accuracy measures of PSMA PET/CT
timeFrame: up to 5 years post-surgery
measure: (Changes) in the EPIC-26 sexual functioning domain score between groups
timeFrame: up to 5 years post-surgery
measure: (Changes in) quality-adjusted life-years (EQ-5D-5L) in patients in the control group vs. intervention group
timeFrame: up to 5 years post-surgery
measure: Total health care related costs (iMTA MCQ) in patients in the control group vs. intervention group
timeFrame: up to 5 years post-surgery
measure: Total loss of productivity and presenteeism (iMTA PCQ) in patients in the control group vs. intervention group
timeFrame: up to 5 years post-surgery
Other outcomes:
Locations:
city: Nijmegen
country: Netherlands
facility: Canisius Wilhelmina Ziekenhuis
state: Gelderland
Study officials:
affiliation: Canisius-Wilhelmina Hospital
name: Jean-Paul A. van Basten
role: PRINCIPAL_INVESTIGATOR
References: