Dutch National Randomized Study: PSMA-PET/CT As a Triage Tool for Pelvic Lymph Node Dissection in Prostatectomy Patients

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.

• Total number of ePLNDs and PSMA PET/CTs performed and their intervention-related healthcare costs [Срок оценки: up to 5 years post-surgery]
• Incidence and types of surgical complications after RARP and ePLND [Срок оценки: up to 1 year post-surgery]
• Total nodes resected on ePLND and number of positive and negative nodes within and outside of the standard ePLND template [Срок оценки: up to 5 years post-surgery]
• Occurrence of pelvic lymph node metastasis and distant metastasis (visceral, bone, distant lymph nodes, pelvic lymph nodes) on PSMA-PET/CT during follow-up [Срок оценки: up to 5 years post-surgery]
• Initiation of salvage therapy [Срок оценки: up to 5 years post-surgery]
• Metastasis-free survival [Срок оценки: up to 5 years post-surgery]
• Hormone-therapy free survival [Срок оценки: up to 5 years post-surgery]
• Diagnostic accuracy measures of PSMA PET/CT [Срок оценки: up to 5 years post-surgery]
• (Changes) in the EPIC-26 sexual functioning domain score between groups [Срок оценки: up to 5 years post-surgery]
• (Changes in) quality-adjusted life-years (EQ-5D-5L) in patients in the control group vs. intervention group [Срок оценки: up to 5 years post-surgery]
• Total health care related costs (iMTA MCQ) in patients in the control group vs. intervention group [Срок оценки: up to 5 years post-surgery]
• Total loss of productivity and presenteeism (iMTA PCQ) in patients in the control group vs. intervention group [Срок оценки: up to 5 years post-surgery]