[68Ga]PSMA-11 PET/CT vs. mpMRI in patients with a high suspicion of prostate cancer and previous negative biopsy: head to head, parallel, prospective trial (PROSPET-BX).

PURPOSE: This prospective imaging trial was designed to compare [68Ga]PSMA-11 PET/CT with multiparametric MRI (mpMRI) in parallel in men with suspicion of prostate cancer (PCa) after at least one previous negative biopsy (ClinicalTrials.gov: NCT05297162; GR-2018-12366240). MATERIALS AND METHODS: Between April 2022 and June 2025, we enrolled 130 patients who met the inclusion criteria and completed protocol investigations. Target lesions were defined based on PI-RADS v2.1 for mpMRI and PRIMARY Score, SUVmax and SUVratio for [68Ga]PSMA-11 PET/CT. Findings were statistically correlated with pathology results. Subsequently, we developed a nomogram to predict clinically significant PCa (csPCa), defined as International Society of Urological Pathology [ISUP] grade ≥ 2, using Boruta’s algorithm for variable selection. RESULTS: Median age in our cohort was 65.5 years (range, 50.5–82.2) and median PSA 9.7 ng/ml (range, 4–35). According to pathology, 20 patients (15.4%) had csPCa, while most had negative biopsies (95;73%). Median SUVmax and SUVratio were 3.9 (range, 1.9–49.9) and 1.5 (range, 1-17.3), respectively, with optimal cut-offs of SUVmax > 6 and SUVratio ≥ 2.8. Diagnostic accuracy for csPCa was significantly higher for PRIMARY score than for PI-RADS (92% vs. 83%; p = 0.0344). Clinical and imaging variables were significantly correlated with csPCa (p < 0.01), with PSA density, PRIMARY score, SUVratio, and PI-RADS emerging as independent predictors. Based on these findings, we developed the PRIMER (PSA density, Radiological Index, Metabolic Evaluation, Re-biopsy setting) nomogram to assess csPCa likelihood, achieving an AUC of 0.8957 in the training set. CONCLUSIONS: [68Ga]PSMA-11 PET/CT outperformers mpMRI in the re-biopsy setting. The developed PRIMER nomogram can predict csPCa likelihood before biopsy.