Head-to-Head Comparison of mpMRI, PSMA, GRPR PET/CT, and PET/CT Plus MRI for Local Staging of Primary Prostate Cancer and Their Prognostic Value

Accurate local staging of primary prostate cancer (PCa) is crucial for guiding therapeutic strategies. Current imaging methods, including MRI and PET/CT, may have variable accuracy in detecting key disease features. This head-to-head study compared the diagnostic performance of prostate-specific membrane antigen (PSMA), gastrin-releasing peptide receptor (GRPR) PET/CT, multiparametric MRI (mpMRI), and combined PET/CT plus MRI for local staging of intermediate-risk and high-risk PCa, along with their prognostic significance. <b>Methods:</b> In this retrospective analysis, patients with intermediate-risk or high-risk PCa underwent mpMRI, [⁶⁸Ga]Ga-PSMA-617 PET/CT, and [⁶⁸Ga]Ga-RM26 (GRPR-targeted) PET/CT before radical prostatectomy. Imaging findings were compared with whole-mount histopathology for local T stage, bilateral intraprostatic disease, extraprostatic extension, and seminal vesicle invasion. The prognostic value for predicting biochemical recurrence-free survival was assessed. <b>Results:</b> Among 81 eligible men, PSMA PET/CT showed higher overall accuracy than GRPR PET/CT (56% vs. 36%, <i>P</i> = 0.011) and improved detection of bilateral intraprostatic disease compared with mpMRI (72% vs. 54%, <i>P</i> = 0.024). In the pure acinar adenocarcinoma subgroup, PSMA PET/CT outperformed both mpMRI and GRPR PET/CT for overall accuracy (58% vs. 39% and 34%, <i>P</i> = 0.029 and 0.005, respectively). The combined PSMA PET/CT plus mpMRI further enhanced staging accuracy compared with mpMRI alone (61% vs. 41%, <i>P</i> = 0.002). Additionally, a local stage T3a or greater based on PSMA PET/CT plus mpMRI was an independent predictor of biochemical recurrence-free survival (hazard ratio, 4.277; <i>P</i> < 0.001), surpassing conventional clinicopathologic factors. <b>Conclusion:</b> PSMA PET/CT, especially when combined with mpMRI, offers superior accuracy in local staging and provides incremental prognostic value beyond standard clinicopathological parameters. Incorporating PET/MRI-derived local staging into clinical decision-making may improve patient stratification, guide surgical or focal therapy strategies, and ultimately enhance patient outcomes.