Staging Accuracy and Prognostic Value of Prostate-Specific Membrane Antigen PET/CT Strongly Depends on Lymph Node Tumor Burden.

: To explore the factors affecting the lymph node metastasis (LNM) detection performance of prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT) and to evaluate its prognostic value for biochemical recurrence after radical prostatectomy (RP). : Patients who had intermediate- or high-risk prostate cancer and underwent robot-assisted (RA)RP between 2017 and 2021 were included. Initial lymph node staging was carried out using PSMA PET/CT. Sensitivity, specificity, and positive (PPV) and negative (NPV) predictive values were calculated. A cut-off value for LNM tumor deposit size that maximizes specificity was investigated and a post hoc specificity analysis was carried out. In survival analysis for biochemical progression-free survival (bPFS) after RP, Kaplan-Meier curves of molecular imaging (mi)N0 and miN1 patients were compared using the log-rank test and separate Cox regression models were developed to reveal the significance of PSMA PET/CT staging in pre- and post-surgery settings. : In 583 patients with a prevalence of pathology-proven LNM of 27.4%, overall sensitivity, specificity, PPV, and NPV of PSMA PET/CT per patient were 26.3% [95%CI 18.9-35.5], 93.9% [95%CI 84.9-100], 61.8% [95%CI 44.5-83.5], and 77.1% [95%CI 69.7-85.1], respectively. PSMA PET/CT showed a better sensitivity as LNM tumor deposit size increased ( = 0.003 OR 2.4 [95%CI 1.3-4.4]) and a better specificity in pT3-4 tumors (96.1%) versus pT2 (91.1%, = 0.024 OR 2.7 [95%CI 1.1-6.3]). After adjustment according to 5.5 mm LNM tumor deposit size, which showed the best discriminative performance (AUC: 0.905 [95%CI 0.804-1.000, < 0.001]), overall sensitivity tripled (90.2%, < 0.001). The 1-year bPFS was 56.0% and 83.3% for miN1 and miN0 patients, respectively ( < 0.001). Whereas miN0pN1 was not, miN1pN1 disease was independently associated with decreased bPFS (HR:2.1 95%CI 1.3-3.4, < 0.001). : PSMA PET/CT has a lymph node tumor burden-dependent and cohort-driven diagnostic ability but consequently a strong independent prognostic value for predicting biochemical recurrence after RARP.