Prostate-specific Membrane Antigen Positron Emission Tomography Versus Conventional Imaging for Preoperative Staging High-risk Prostate Cancer Patients Undergoing Surgery for cN0M0 Disease: An European Association of Urology-Young Academic Urologists Prostate Cancer Working Group Multi-institutional Study.

Background and objective: Current guidelines strongly recommend prostate-specific membrane antigen positron emission tomography (PSMA-PET) for staging high-risk prostate cancer (PCa) patients. This study aims to evaluate the impact of staging procedure (PSMA-PET vs conventional imaging) on short-term oncologic outcomes in a cohort of N0M0 high-risk PCa patients who underwent radical prostatectomy (RP) and extended pelvic lymph node dissection (ePLND). Methods: We retrospectively included 1475 high-risk PCa patients who underwent RP and ePLND in 14 referral centers between 2014 and 2024. Each patient underwent either PSMA-PET (miN0M0) or conventional imaging (cN0M0). After a landmark analysis and 1:1 propensity score matching for age at diagnosis, year of surgery, initial serum prostate-specific antigen (PSA), cT stage, and International Society of Urological Pathology grade group at biopsy, the Kaplan-Meier methodology was used to assess biochemical recurrence (BCR)-free survival (BCR-FS) and multivariable Cox regression models to identify the predictors of BCR (time in months between the date of RP and the date of BCR). Key findings and limitations: After propensity score matching, 463 (48.2%) versus 463 (90.1%) patients underwent PSMA-PET versus conventional imaging. PSA persistence was observed in 15 (3.2%) versus 64 (14%) miN0M0 patients at PSMA-PET versus cN0M0 patients at conventional imaging (p < 0.001). The BCR-FS rates at 36 mo were 90.9% and 82.2% in the PSMA-PET and conventional imaging cohorts, respectively. At multivariate Cox regression analyses, PSMA-PET (hazard ratio: 0.48; 95% confidence interval: 0.29-0.77) was an independent predictor of lower BCR rates (p = 0.003). In the PSMA-PET cohort, BCR-FS rates were similar between patients with one high-risk feature and those with two or more high-risk features, while in the conventional imaging cohort, two or more high-risk features were associated with significantly worse BCR-FS rates than one high-risk feature. Limitations include the retrospective design of the study. Conclusions and clinical implications: Time to biochemical recurrence was longer in the miN0M0 cohort than in the cN0M0 cohort. Superior PSMA-PET staging accuracy seems to improve short-term oncologic outcomes of high-risk PCa patients following surgery.