Histology and PSMA Expression on Immunohistochemistry in High-Risk Prostate Cancer Patients: Comparison with (68)Ga-PSMA PET/CT Features in Primary Staging

SIMPLE SUMMARY: The aim of this study was to correlate primary staging prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) parameters with either prostate final histopathology (pT) or PSMA-immunochemistry (IHC) features in a cohort of high-risk prostate cancer (PCa) patients. Our study demonstrated a correlation between higher SUVmax and IHC-PSMA expression. Moreover, we found correlations between higher total lesion PSMA (PSMA-TL) values and the risk of lymphovascular invasion (LVI), and between PSMA tumor volume (PSMA-TV) and the presence of a cribriform pattern. Our results, if validated by further studies, may help to better identify unfavorable features showed by PSMA-PET/CT in primary staging, thus improving patients’ management. ABSTRACT: PSMA-PET/CT is a suitable replacement for conventional imaging in the primary staging of PCa. The aim of this retrospective study was to assess the correlation between parameters discovered by PSMA PET/CT in primary staging and either prostate histopathology (pT) findings or PSMA-IHC expression in a cohort of biopsy-proven high-risk PCa candidates for surgery. Clinical information (age, iPSA-value, and grading group) and PSMA-PET/CT parameters (SUVmax, PSMA tumor volume [PSMA-TV], and total lesion [PSMA-TL]) were compared with pT (including histologic pattern, Gleason grade, and lymphovascular invasion [LVI]) and PSMA-IHC features, including visual quantification (VS) with a four-tiered score (0 = negative, 1+ = weak, 2+ = moderate, 3+ = strong), growth pattern (infiltrative vs expansive), and visual pattern (cytoplasmic vs membranous). In total, 44 patients were enrolled, with a median age of 67 (IQR 57-77); the median iPSA was 9.4 ng/dL (IQR 12.5-6.0). One patient (3%) was grading group (GG) 3, 27/44 (61%) were GG4, and 16/44 (36%) were GG5. PSMA-PET/CT detection rate for the presence of primary prostate cancer was 100%. Fused/poorly formed Gleason grade 4 features were predominant (22/44–50%); a cribriform pattern was present in 18/44 (41%) and acinar in 4/44 (9%). We found that lower PSMA-TVs were mostly related to acinar, while higher PSMA-TVs correlated with a higher probability to have a cribriform pattern (p-value 0.04). LVI was present in 21/44(48%) patients. We found that higher PSMA-TV and PSMA-TL are predictive of LVI p-value 0.002 and p-value 0.01, respectively. There was no correlation between PET-parameters and perineural invasion (PNI), probably because this was present in almost all the patients. Moreover, patients with high PSMA-TL values displayed the highest PSMA-IHC expression (VS3+) with a membranous pattern. In conclusion, PSMA-TV and PSMA-TL are predictors of a cribriform pattern and LVI. These conditions are mostly related to higher aggressiveness and worse outcomes.