External Validation and Addition of Prostate-specific Membrane Antigen Positron Emission Tomography to the Most Frequently Used Nomograms for the Prediction of Pelvic Lymph-node Metastases: an International Multicenter Study

Background: Different nomograms exist for the preoperative prediction of pelvic lymph-node metastatic disease in individual patients with prostate cancer (PCa). These nomograms do not incorporate modern imaging techniques such as prostate-specific membrane antigen (PSMA) positron emission tomography (PET). Objective: To determine the predictive performance of the Briganti 2017, Memorial Sloan Kettering Cancer Center (MSKCC), and Briganti 2019 nomograms with the addition of PSMA-PET in an international, multicenter, present-day cohort of patients undergoing robot-assisted radical prostatectomy (RARP) and extended pelvic lymph-node dissection (ePLND) for localized PCa. Design, setting, and participants: All 757 eligible patients who underwent a PSMA-PET prior to RARP and ePLND in three reference centers for PCa surgery between January 2016 and November 2020 were included. Outcome measurements and statistical analysis: Performance of the three nomograms was assessed using the receiver operating characteristic curve–derived area under the curve (AUC), calibration plots, and decision curve analyses. Subsequently, recalibration and addition of PSMA-PET to the nomograms were performed. Results and limitations: Overall, 186/757 patients (25%) had pelvic lymph-node metastatic (pN1) disease on histopathological examination. AUCs of the Briganti 2017, MSKCC, and Briganti 2019 nomograms were 0.70 (95% confidence interval [95% CI]: 0.64–0.77), 0.71 (95% CI: 0.65–0.77), and 0.76 (95% CI: 0.71–0.82), respectively. PSMA-PET findings showed a significant association with pN1 disease when added to the nomograms (p < 0.001). Addition of PSMA-PET substantially improved the discriminative ability of the models yielding cross-validated AUCs of 0.76 (95% CI: 0.70–0.82), 0.77 (95% CI: 0.72–0.83), and 0.82 (95% CI: 0.76–0.87), respectively. In decision curve analyses, the addition of PSMA-PET to the three nomograms resulted in increased net benefits. Conclusions: The addition of PSMA-PET to the previously developed nomograms showed substantially improved predictive performance, which suggests that PSMA-PET is a likely future candidate for a modern predictive nomogram. Patient summary: Different tools have been developed to individualize the prediction of prostate cancer spread to lymph nodes before surgery. We found that the inclusion of modern imaging (prostate-specific membrane antigen positron emission tomography) improved substantially the overall performance of these prediction tools.