Background: Multi-parametric magnetic resonance imaging (mpMRI) is validated for the diagnosis of clinically significant prostate cancer (csPCa). 68Ga-PSMA -11 PET/CT (PSMA-PET/CT) combined with mpMRI has improved negative predictive value over mpMRI alone for csPCa. The aim of this post-hoc analysis of the PRIMARY study was to evaluate the clinical significance of patterns of intra-prostatic PSMA activity, proposing a 5- point PRIMARY score to optimise accuracy of PSMA-PET/CT for csPCa in a low prevalence population. Methods: The PRIMARY trial is a prospective multi-centre phase II imaging trial that enrolled biopsy-naïve men with suspected PCa, no prior biopsy, recent mpMRI (6 months) and planned for prostate biopsy. 291 men underwent mpMRI, PSMA-PET/CT and systematic +/- targeted biopsy. The mpMRI was read separately using PI-RADS (V2). PSMA-PET/CT (pelvic only) was acquired a minimum 60 minutes post injection. PSMA-PET/CT was centrally read for pattern (diffuse transition zone (TZ), symmetrical central zone (CZ), focal TZ or peripheral zone (PZ), and intensity (SUVmax). In this post-hoc analysis, a 5-level PRIMARY score was assigned based on analysis of the central read: 1. No pattern, 2. Diffuse TZ or CZ (no focal), 3. Focal TZ, 4. Focal PZ or 5. SUVmax ≥ 12. Two further readers independently assigned a PRIMARY score to 118 scans for inter-rater agreement. Associations between PRIMARY score and csPCa (ISUP≥2) were evaluated. Results: Of 291 men enrolled, 162 (56%) had csPCa. PRIMARY score-1 was present in 16% (47), score-2 in 19% (55), score-3 in 10% (29), score-4 in 40% (117) and score-5 in 15% (43). The proportion of patients with csPCa and PRIMARY score 1 to 5 was 8.5% (4/47), 27% (15/55), 38% (11/29), 76% (89/117) and 100% (43/43) respectively. Sensitivity, specificity, PPV and NPV for PRIMARY score 1,2 (low-risk patterns) vs PRIMARY score 3-5 (high-risk patterns) was 88%, 64%, 76% and 81%, compared to 83%, 53%, 69% and 72% for PI-RADS (2 vs 3-5) on mpMRI. The inter-rater agreements for PRIMARY score 1,2 vs. PRIMARY score 3-5 was 0.76 (CI: 0.64-0.88) and 0.64 (CI: 0.49-0.78). Conclusion: A PRIMARY score incorporating intra-prostatic pattern and intensity on PSMA-PET/CT shows potential with high diagnostic accuracy for csPCa. Further validation is warranted prior to implementation.
Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 2022 Mar 17 [Epub ahead of print]
Louise M Emmett, Nathan Papa, James Buteau, Bao Ho, Victor Liu, Matthew Roberts, James Thompson, Daniel Moon, Gemma Sheehan-Dare, Omar Alghazo, Shikha Agrawal, Declan G Murphy, Phillip Stricker, Thomas A Hope, Michael Hofman
Department of Theranostics and Nuclear Medicine, St Vincent's Hospital Sydney, Australia., School of Public Health and Preventive Medicine, Monash University, Australia., Molecular Imaging and Therapeutic Nuclear Medicine, Peter MacCallum Cancer, Melbourne., Department of Urology, Royal Brisbane and Women's Hospital, Brisbane., Department of Urology, St. George Hospital, Australia., Division of Cancer Surgery, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia., Gosford Hospital., Garvan Institute of Medical Research., Peter MacCallum Cancer Centre., St. Vincent's Prostate Cancer Centre, Darlinghurst, NSW, Australia., University of California, San Francisco., Peter MacCallum Cancer Centre, Melbourne, Australia.