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Introduction: Accurate preoperative nodal staging is crucial for treatment planning in prostate cancer (PCa). Extended pelvic lymph node dissection (ePLND) is recommended from intermediate-risk onward but is invasive. This study evaluated the diagnostic accuracy of PSMA-PET/CT as a noninvasive staging method by comparing imaging-based lymph node positivity (cN+) with postoperative histopathology (pN+). Methods: This retrospective, monocentric analysis included 59 with unfavorable intermediate- and high-risk PCa patients (NCCN criteria) who underwent robotic-assisted radical prostatectomy with ePLND and preoperative PSMA-PET/CT staging. Sensitivity, specificity, positive (PPV) and negative predictive values (NPV) were calculated for the overall cohort and risk subgroups. The interaction between PSMA-PET and the number of resected lymph nodes was assessed using multivariate logistic regression. Results: pN+ was found in 27.1% of patients. PSMA-PET/CT showed 97.7% specificity and a PPV of 90.9%. Sensitivity was 62.5% and similar for intermediate- and high-risk subgroups. Six false-negative findings were identified. Multivariate analysis confirmed that diagnostic accuracy of PSMA-PET/CT was independent of the number of lymph nodes dissected during ePLND (interaction term p = 0.38). Conclusion: PSMA-PET/CT provides high specificity and PPV for primary lymph node staging in unfavorable intermediate- and high-risk PCa but shows only moderate sensitivity. A negative PSMA-PET/CT cannot reliably replace ePLND due to the risk of understaging.

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