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 accu racy 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 expres sion 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). Regres sion models tested the immunohistochemical PSMA expression in block and the PSMA PET/CT maximum standardized uptake value biopsy/vesicoprostatic (SUVmax). Key findings and limit between PSMA expres interval {CI} 0.7–0.9], ations: A statistically significant strong correlation was found sion in biopsy and vesicoprostatic block (AC1 = 0.8 [confidence p < 0.01). According to the multivariable linear regression models, PCa-positive biopsy cores and the index lesion were statistically sig f SUVmax (b = 3.3, CI 1.5–7.5, p < 0.01 and b = 4.9, CI 1.8–13, p < 0.01, theIRSsofboththe nificantpredictorso respectively). Limitations includemanual interpretation of immunohistochemistry, potentialmodeloverfitting,and a shortfollow-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.Theassessmentof immunohistochemicalPSMAexpressioninapreoperative settingmayhaveimplicationsfordeterminingamoreaccurate,patient-specificdiagnos ticpathway. ©2025 European Association of Urology. Published by Elsevier B.V. All rights are reserved, includingthosefortextanddatamining,AItraining,andsimilartechnologies.