Nodal maximum standardised uptake value improves PSMA-PET/CT-based nodal staging in intermediate- and high-risk prostate cancer

Objectives: To evaluate whether nodal maximum standardised uptake value (SUVmax) improves the positive predictive value (PPV) of prostate-specific membrane antigen (PSMA) positron emission tomography (PET)/computerised tomography (CT) for detecting lymph node invasion (LNI) in prostate cancer (PCa), and to develop clinical decision tools to guide decision-making for patients with low- and high-volume nodal disease. Patients and Methods: This international multicentre study included patients with histopathologically confirmed PCa who underwent preoperative PSMA-PET and robot-assisted radical prostatectomy with extended pelvic lymph node dissection (2016–2023). Sensitivity, specificity, PPV, and negative predictive value (NPV) for LNI detection were calculated, defining a positive test as non-physiological PSMA uptake classified according to the Prostate Cancer Molecular Imaging Standardised Evaluation (PROMISE) molecular imaging Tumour-Node-Metastasis (miTNM) system. Receiver operating curves analysis identified optimal nodal SUVmax cut-offs for pelvic LNI. Logistic regression assessed predictors for pathological N1 stage (pN1) and high-volume nodal disease (four or more positive nodes). Clinical decision tools were developed to stratify patients into three risk groups for pN1 and high-volume nodal disease. Results: A total of 521 patients were included, with a median (interquartile range) age of 66 (61–71) years and prostate-specific antigen (PSA) level of 9.9 (6.6–17.0) ng/mL. The PSMA-PET showed 45.0% sensitivity, 94.3% specificity, 64.7% PPV, and 88.3% NPV for LNI detection. Adding nodal SUVmax ≥4.9 improved the PPV to 81.1% and sensitivity to 71.4% and, combined with a PSA level ≥10 ng/mL, magnetic resonance imaging (MRI) T-stage ≥T3a, and miT-stage ≥T3a, identified 95% of pN1 cases in the high-risk group. High-volume nodal disease was found in 3.8%, including 1.1% in miN0 patients. Nodal SUVmax ≥7.2, MRI T-stage ≥T3a, and miN2 (multiple suspicious LNs) were predictors for high-volume nodal disease and, combined in a clinical decision tool, excluded all low-risk patients for high-volume nodal disease. Conclusion: Nodal SUVmax improves PPV of PSMA-PET for nodal staging and aids in excluding high-volume nodal disease. Clinical decision tools integrating nodal SUVmax with relevant clinical parameters demonstrate potential to guide individualised nodal management. These findings warrant external validation in larger cohorts.