Association of [68Ga]Ga-PSMA-11 PET/CT Metrics with PSA Persistence Following Radical Prostatectomy in Patients with Intermediate- and High-Risk Prostate Cancer

<b>Background/Objectives:</b> The aim of this study was to determine whether semiquantitative and volume-based metrics obtained from [⁶⁸Ga]Ga-PSMA-11 PET/CT (PSMA-PET) scans before radical prostatectomy (RP) are associated with PSA persistence after surgery in patients with intermediate- (IR) and high-risk (HR) prostate cancer (PCa). <b>Methods:</b> We included 118 consecutive patients (IR = 57; HR = 61) with PCa with a PSMA-PET for initial staging and underwent subsequent RP. Clinical parameters and PSMA-PET metrics in the prostate were obtained to determine the following measurements: SUVmax, SUVmean, Target-to-Background Ratios (TBRs), Prostate Molecular Tumor (pMTV), Prostate Total Lesion Activity (pTLA), Prostate Volume (pV), and Prostate Disease Burden (pDB). The association of PSMA-PET metrics parameters before RP and PSA persistence were analyzed by multivariate logistic regression. <b>Results:</b> SUVmax and volume-based PSMA-PET metrics were significantly higher in patients with ISUP Grade 3-5 vs. ISUP Grade 1-2, and only pMTV, pTLA, and pDB were found to be significantly higher in HR patients, as compared with the IR group. During follow-up, 23 patients showed PSA persistence. pMTV, pTLA, and pDB were significantly higher among patients presenting PSA persistence after RP than in patients with undetectable PSA. Multivariate logistic regression analysis found that lymph node infiltration and pTLA were independent predictors for PSA persistence. A cut-off point of ≥25.1 allowed the best discrimination for PSA persistence (OR: 7.4; IQR: 1.4-39.1; <i>p</i> < 0.05). <b>Conclusions:</b> The identified association between PSA persistence and prostate TLA of PSMA-PET at initial staging highlights its potential as a valuable tool to improve risk prediction in prostate cancer patients. Further research is needed to confirm these results.