A prospective randomized multicentre study of the impact of gallium-68 prostate-specific membrane antigen (PSMA) PET/CT imaging for staging high-risk prostate cancer prior to curative-intent surgery or radiotherapy (proPSMA study): clinical trial protocol

Background: Accurate staging of patients with prostate cancer (PCa) is important for therapeutic decision-making. Relapse after surgery or radiotherapy of curative intent is not uncommon and, in part, represents a failure of staging with current diagnostic imaging techniques to detect disease spread. Prostate-specific membrane antigen (PSMA) positron-emission tomography (PET)/computed tomography (CT) is a new whole-body scanning technique that enables visualization of PCa with high contrast. The hypotheses of this study are that: (i) PSMA-PET/CT has improved diagnostic performance compared with conventional imaging; (ii) PSMA-PET/CT should be used as a first-line diagnostic test for staging; (iii) the improved diagnostic performance of PSMA-PET/CT will result in significant management impact; and (iv) there are economic benefits if PSMA-PET/CT is incorporated into the management algorithm. Objectives and Methods: The proPSMA trial is a prospective, multicentre study in which patients with untreated high-risk PCa will be randomized to gallium-68-PSMA-11 PET/CT or conventional imaging, consisting of CT of the abdomen/pelvis and bone scintigraphy with single-photon emission CT/CT. Patients eligible for inclusion are those with newly diagnosed PCa with select high-risk features, defined as International Society of Urological Pathology grade group ≥3 (primary Gleason grade 4, or any Gleason grade 5), prostate-specific antigen level ≥20 ng/mL or clinical stage ≥T3. Patients with negative, equivocal or oligometastatic disease on first line-imaging will cross over to receive the other imaging arm. The primary objective is to compare the accuracy of PSMA-PET/CT with that of conventional imaging for detecting nodal or distant metastatic disease. Histopathological, imaging and clinical follow-up at 6 months will define the primary endpoint according to a predefined scoring system. Secondary objectives include comparing management impact, the number of equivocal studies, the incremental value of second-line imaging in patients who cross over, the cost of each imaging strategy, radiation exposure, inter-observer agreement and safety of PSMA-PET/CT. Longer-term follow-up will also assess the prognostic value of a negative PSMA-PET/CT. Outcome and Significance: This trial will provide data to establish whether PSMA-PET/CT should replace conventional imaging in the primary staging of select high-risk localized PCa, or whether it should be used to provide incremental diagnostic information in selected cases.