A Dual-Threshold Strategy Enables Reliable Biopsy-Free Diagnosis of High-Risk Prostate Cancer.

[BACKGROUND] Several studies have suggested that biopsy-free radical prostatectomy reduces burdens for selected prostate cancer (PCa) patients pre-screened by clinical indicators and PSMA-PET/CT. However, the absence of pre-operative pathology precludes high-risk PCa (HRPCa) identification, crucial for determining the need for extended pelvic lymph node dissection (ePLND). We evaluated whether combining pre-operative clinical indicators and ¹⁸F-PSMA-1007 PET/CT could non-invasively stratify HRPCa risk.

[METHODS] This retrospective diagnostic study included a development cohort of 93 patients from USTC center, as well as two external validation cohorts: one cohort of 83 patients from XYH Hospital and another cohort of 117 patients from XJH Hospital. All enrolled patients met the USTC model value ≥ 0.6 criteria (assessed using a nomogram composed of PSAD and PI-RADS grade) and obtained definitive pathological results within 4 weeks after ¹⁸F-PSMA-1007 PET/CT examination. Patients were stratified as HRPCa (D'Amico criteria: tPSA> 20 ng/mL, GS ≥ 8, or ≥ cT2c) or non-high-risk (NHR). Maximum standardized uptake value (SUVmax) and target-to-background ratios (TBRs) of PSMA-PET/CT were quantified. Diagnostic performance for HRPCa was evaluated using ROC analysis. Multivariate logistic regression analysis identified independent predictors.

[RESULTS] In the development cohort (n = 93), SUVmax (AUC = 0.807) and tPSA (AUC = 0.777) demonstrated good discriminatory performance for identifying HRPCa (both p < 0.05). The dual-threshold criterion (SUVmax> 20.9 and tPSA> 15.09 ng/mL) achieved a consistently high PPV (up to 100% in the development cohort and > 91% in external validation) and specificity, significantly outperforming single parameters (p < 0.001). In two external validation cohorts, similar diagnostic performance was observed.

[CONCLUSION] A dual-threshold non-invasive strategy is established for predicting HRPCa in biopsy-free radical prostatectomy candidates pre-screened by the USTC model, while its applicability to unscreened or low to intermediate-risk populations remains unproven.