Immunohistochemical Prostate-specific Membrane Antigen (PSMA) Expression Patterns of Primary Prostate Cancer Tissue as a Determining Factor for Prostate Cancer Staging with PSMA Positron Emission Tomography/Computed Tomography.

Background and objective: In recent studies, prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) has shown accuracy in staging patients diagnosed with prostate cancer. Here, we aim to evaluate the correlation between PSMA immunohistochemical characteristics of prostate cancer (PCa)-positive biopsy cores and whole-mount specimens, and test the predictive role of PSMA expression in biopsy samples for staging PSMA PET/CT.

Methods: A total of 104 patients with high- or intermediate-risk PCa who underwent [68Ga]Ga-PSMA-11 PET/CT before radical prostatectomy were prospectively selected between June 2021 and July 2023. The analysis of immunohistochemical PSMA expression was performed using the Immunoreactive Score (IRS). The correlation between biopsy and final specimen was evaluated using Gwet's agreement coefficient for ordinal variables (AC1). Regression models tested the immunohistochemical PSMA expression in biopsy/vesicoprostatic block and the PSMA PET/CT maximum standardized uptake value (SUVmax).

Key findings and limitations: A statistically significant strong correlation was found between PSMA expression in biopsy and vesicoprostatic block (AC1 = 0.8 [confidence interval {CI} 0.7-0.9], p < 0.01). According to the multivariable linear regression models, the IRSs of both the PCa-positive biopsy cores and the index lesion were statistically significant predictors of SUVmax (β = 3.3, CI 1.5-7.5, p < 0.01 and β = 4.9, CI 1.8-13, p < 0.01, respectively). Limitations include manual interpretation of immunohistochemistry, potential model overfitting, and a short follow-up.

Conclusions and clinical implications: The immunohistochemical analysis of PSMA expression in PCa-positive biopsy cores showed a high correlation with the whole-mount specimen. The degree of PSMA expression is an independent predictor of SUVmax. The assessment of immunohistochemical PSMA expression in a preoperative setting may have implications for determining a more accurate, patient-specific diagnostic pathway.