PSMA-Directed PET/MRI Enables Noninvasive Diagnosis and Prognosis in Patients with Increased PSA Levels: Results from the Prospective Randomized RAPID Trial

Systematic transrectal ultrasound-guided biopsy lacks accuracy in the primary diagnosis of prostate cancer (PCa) and causes side effects. We investigated prostate-specific membrane antigen (PSMA)-targeted PET/MRI as a less-invasive alternative for biopsy guidance and risk assessment. <b>Methods:</b> The RAPID study was a randomized, controlled, single-center, open-label phase 3 trial comparing the diagnostic efficacy of ⁶⁸Ga-PSMA-11 PET/MRI with systematic transrectal ultrasound-guided prostate biopsy. In total, 220 men with suspected PCa were randomized to either a standard (random 12-core biopsy; RB) group or an image-guided biopsy (IGB) group. Biopsy, prostatectomy histology, and follow-up visits served as references. <b>Results:</b> PET/MRI prospectively predicted 91 of 113 histologically verified tumors, corresponding to a sensitivity of 80.5% and a positive predictive value of 84.3%. Among tumors characterized as ISUP GG of 3 or greater (<i>n</i> = 60), PSMA PET/MRI prospectively detected 95% (<i>n</i> = 57). The IGB group demonstrated slightly higher sensitivity, specificity, positive predictive value, and negative predictive value compared with the RB group (79.3%, 94.7%, 85.2%, 92.2% vs. 74.2%, 88.0%, 71.9%, 89.2%). Seventy-nine patients were eligible for a direct IGB and RB subanalysis, with IGB detecting 15 additional cases. PET/MRI showed high specificity (94%) and negative prediction (86%) for tumor aggressiveness. In a median follow-up period of 3 y, an aggressive course of disease was detected in 25 of 199 patients. RB correlation identified 24 patients with an ISUP GG of 3 or greater with aggressive disease development during follow-up, compared with 23 patients identified by PET/MRI. Negative prediction of both methods was comparably high at 99%; however, PET/MRI overestimated fewer patients (21) as aggressive compared with RB (34). <b>Conclusion:</b> PSMA-targeted PET/MRI-guided biopsy is a reliable, less invasive method for detecting and characterizing PCa in a cohort with moderately increased PSA values, potentially reducing unnecessary biopsies and provides a reliable prognosis of the course of disease. These results support the integration of modern imaging techniques into clinical practice to improve the treatment of PCa.