Objectives: To assess the predictive accuracy (PA), the best cut-off value and the clinical impact of a recent published nomogram aimed to predict the positivity of 68Ga-labeled Prostate-specific Membrane Antigen–ligand Positron-emission Tomography/Computed Tomography (PSMA-PET/CT) in patients with Biochemical Recurrent Prostate Cancer After Radical Prostatectomy, through an external validation.
Methods: 413 Prostate Cancer (PCa) patients with evidence of biochemical recurrence (BCR) after radical prostatectomy and Prostate Specific Antigen (PSA) value between 0.2 and 1 ng/ml were investigated at single tertiary center with PSMA PET/CT. Multivariate logistic regression were performed to assess the predictors of positive PSMA PET/CT results in patients-based analysis. External validation was performed using regression coefficients (PSA at PSMA-PET/CT, Pathologic ISUP Group and ADT at time of PSMA-PET/CT) of the compact model of the previously published nomogram. The performance characteristics of the model were assessed by quantifying PA, according to model calibration, in order to graphically investigate the extent of overestimation or underestimation. Moreover, specificity, sensitivity, positive predictive value (PPV) and negative predictive value (NPV) for each nomogram’s derived probability cut off were systematically analyzed and Yuden’s index was used to find the best nomogram’s cut off. Finally, decision curve analysis (DCA) was implemented, in order to quantify the nomogram's clinical value in routine practice.
Results: Overall detection rate of PSMA-PET/CT was 44% (182/413). Lesions indicative of PCa recurrence at PSMA-PET/CT were found in 36% (83/249) and 55% (99/164) of patients with PSA 0.2-0.5 ng/mL and PSA >0.5-1 ng/mL, respectively. At multivariate analysis, PSA at PSMA-PET/CT (OR: 7.06, p<0.001) and ADT at time of PSMA-PET/CT (OR: 2.07, p=0.03) were independent predictors of PSMA-PET/CT positivity (Table 2). PA of the external validation was comparable to PA of the internal validation (64% vs. 67%, respectively, Figure 1) with suboptimal calibration curve. The best nomogram’s cut-off to predict positive PSMA PET/CT was 35 (specificity, sensitivity and accuracy of 64%, 58% and 61% 95%CI=0.55-0.66 respectively, Table 3). Finally, in DCA the nomogram revealed a net benefit when compared with the scenarios of treating all patients or none (Figure 2).
Conclusions: In an external setting, the compact nomogram showed a suboptimal PA as referred to the original population. Nomogram total points values of ≥35 emerged as the best cut-off point to detect lesions indicative of PCa recurrence at PSMA-PET/CT. However, DCA showed a clinical net benefit, suggesting a clinical implication to correctly restage PCa patients.
