Primary Metastasis Staging Using 18F-PSMA-1007 PET-CT in High-Risk Prostate Cancer: A Prospective Comparative Study of Advanced and Traditional Imaging Modalities

Background: Computed tomography (CT) and bone scintigraphy are the imaging modalities currently used for primary metastasis staging of high-risk prostate cancer (PCa). This trial compared these standard staging modalities with potentially more accurate imaging modalities: single photon emission computed tomography-CT (SPECT-CT), magnetic resonance imaging (MRI), prostate specific membrane antigen positron emission tomography (PSMA PET). Methods: This prospective, registered, single-centre, open-label, single-arm trial enrolled patients with primary high-risk PCa. Results of bone scintigraphy and CT were compared with 99mTc-HMDP SPECT-CT, 1.5T whole-body MRI using diffusion-weighted imaging and 18 F-PSMA-1007 PET-CT. Each imaging modality was reviewed by two independent experts blinded for the other modalities. The lesions were classified as benign, equivocal or malignant. Pessimistic and optimistic analyses were performed to resolve equivocal lesion status. Based on clinical data, including follow-up investigations, the best valuable comparator was defined at lesion level in multidisciplinary consensus meetings. Findings: 79 men were included and underwent all imaging modalities, except for one cancelled MRI due to claustrophobia. Mean age was 70 years and median PSA 12 ng/ml (range: 3-2000). Metastatic disease was detected in 27 (34%) patients. In pessimistic and optimistic analysis at patient, region and lesion levels, PSMA PET-CT was superior to all other modalities concerning sensitivity, and the area under curve values (AUC) at the bone region, while maintaining high specificity and demonstrating the highest inter-reader agreement. AUC for detection of bone metastasis for PSMA PET-CT was 0·94 (95%Cl;0·90-0·99) and 0·96 (95%CI;0·92-0·99) (reader 1, and reader 2, respectively) while AUC for all other modalities was in the range of 0·55-0·76. PSMA PET-CT revealed metastatic disease in 18/27 patients where standard imaging was negative. Interpretation: 18F-PSMA-1007 PET-CT outperformed other imaging methods in primary metastasis staging of high-risk PCa. We recommend further evaluation of this method as a new reference standard. Trial Registration number: (ClinicalTrials.gov NCT03537391). Funding Statement: This study was financially supported by grants from Finnish Government Research and Development Funds for Medical Research, Turku University Hospital and TYKS-SAPA Research Fund. Declaration of Interests: Dr. Anttinen reports grants from Profound Medical Inc, Finnish Urological Research Foundation and Finnish Urological Association, outside the submitted work. Dr. Ettala reports non-financial support from Ferring Pharmaceuticals Inc, SwanMedica and Pierre-Fabre Pharma Norden AB, and personal fees from Astellas, outside the submitted work. Dr. Sandell reports personal fees from Roche, outside the submitted work. Dr. Taimen reports personal fees from Roche, AstraZeneca and MSD, and non-financial support from MSD, all outside the submitted work. Dr. Bostrom reports grants from the Cancer Foundation Finland, personal fees from Profound Medical Inc and Janssen-Cilag Company, outside the submitted work. The other authors declare that there is no conflict of interest regarding the publication of this article. Ethical Approval Statement: The trial protocol, included in the Supplemental material, was approved by the ethics committee of the Hospital District of Southwest Finland, and written informed consent was obtained from all participants. The trial was performed in accordance with the principles of the Declaration of Helsinki.