The PRIMARY Score: Using intra-prostatic PSMA PET/CT patterns to optimise prostate cancer diagnosis.

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 (SUV_max). 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. SUV_max ≥ 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.