Comparison of PSMA immunohistochemistry scoring systems to parametric [18F]PSMA-1007 PET/MRI in primary prostate cancer

Purpose Quantification of PSMA expression via PSMA PET is well-established, however quantification of PSMA via immunohistochemistry (IHC) is not standardized. Our aim was to determine the most optimal PSMA IHC scoring system to quantify PSMA expression with PSMA PET as reference standard. Methods Primary intermediate- and high-risk prostate cancer patients received an [F-18]PSMA-1007 PET/MRI followed by radical prostatectomy. SUVmax, SUVmean and K-i of the prostate tumor was determined. Prostate tumors were stained with anti-PSMA antibodies and scored by 2 readers via 10 IHC scoring systems: histochemical score (H-score), immunoreactivity score(predominant intensity) (IRSpredominant intensity), IRS classification(predominant intensity), IRSmean intensity, IRS classification(mean intensity), Allred score, predominant expression pattern, Shannon diversity index (SDI), percentage negatively stained cells and total percentage positively stained cells. Spearman's rank correlation coefficients (rho) were calculated between PET parameters and IHC scoring systems. Interreader agreement for the IHC scoring systems was measured by the intraclass correlation coefficient (ICC). Results Fifty tumors in 46 patients were analysed. H-score had the best correlation with SUVmax (rho 0.615 p < 0.0001) and SUVmean (rho 0.570, p < 0.0001) and the second best correlation with Ki (rho 0.411, p = 0.0030). SDI had the best correlation with Ki (rho -0.440, p = 0.0014) and the second best correlation with SUVmax (rho -0.516, p = 0.0001) and SUVmean (rho -0.490, p = 0.0003). A moderate interreader agreement was observed for H-score (ICC 0.663, 95% CI 0.495-0.797) and SDI (ICC 0.546, 95% CI 0.354-0.725). Conclusion H-score had the best correlation with PSMA PET quantification and an acceptable interreader agreement. Therefore, we deem H-score the most optimal PSMA IHC scoring system.