Biochemical Recurrence–Free Survival After Radical Prostatectomy in Patients with High-Risk Prostate Cancer: A Nationwide Study of PSMA PET/CT Versus Conventional Imaging

Prostate-specific membrane antigen (PSMA) PET/CT offers excellent accuracy in the staging of high-risk prostate cancer (PCa), yet outcomes-based evidence of the clinical benefit remains limited. We aimed to determine whether the rates of biochemical recurrence-free survival (BRFS) are influenced by PSMA-based staging compared with that of conventional imaging among patients undergoing radical prostatectomy (RP), using real-world data and exploiting regional variation in the adoption of PSMA PET/CT across Denmark. <b>Methods:</b> This nationwide cohort study included men with high-risk PCa who underwent RP between 2016 and 2023. Patients were classified on the basis of whether they underwent PSMA PET/CT or conventional imaging before surgery. The primary outcome was BRFS, with overall survival as the secondary outcome. The outcomes were analyzed by inverse probability weighting and adjusted Cox proportional hazards regression analyses. <b>Results:</b> Among 3,279 eligible patients with high-risk PCa who underwent RP, 959 (29.3%) underwent preoperative PSMA PET/CT. This group had a higher 5-y BRFS rate than did the conventional imaging group (65.1%; 95% CI, 61.4%-68.7% vs. 61.1%; 95% CI, 58.9%-63.2%, respectively; weighted hazard ratio, 0.82; 95% CI, 0.70-0.96; <i>P</i> = 0.014). The difference was most pronounced in patients with Gleason scores of 8-10, with 62.5% in the PSMA PET/CT group (95% CI, 57.7%-67.2%) versus 48.9% in the conventional imaging group (95% CI, 44.9%-52.9%; hazard ratio, 0.61; 95% CI, 0.51-0.74; <i>P</i> < 0.001). Overall survival was also greater in the PSMA PET/CT group; however, the limited follow-up prohibited any firm conclusions. The main limitation of this study was its observational design. <b>Conclusion:</b> The use of PSMA PET/CT for high-risk PCa staging was associated with increased BRFS rates.