Immunohistochemical Validation of PSMA Expression Measured by ⁶⁸Ga-PSMA PET/CT in Primary Prostate Cancer

Abstract

Ga-labeled prostate-specific membrane antigen (Ga-PSMA) PET/CT has a proven role in staging and restaging of prostate cancer (PCA). The aims of this study were to evaluate the association of intraprostatic Ga-PSMA PET/CT findings and PSMA expression in immunohistochemical staining and generate a cutoff value for differentiation between normal prostate (PN) and PCA. The data of 31 patients (mean age, 67.2 y) who underwent prostatectomy and preoperative PET were retrospectively analyzed. On PET, focally increased uptake in the prostate was suggestive of tumor. A region of interest was placed on the suggestive area to generate an SUV; a similar region of interest was placed on adjacent visually PN. Both PCA and PN were stained with monoclonal anti-PSMA antibody (clone 3E6, 1:100, M3620). All intraprostatic PCA lesions on PET could be confirmed histopathologically. In PN sections ( = 31), median staining intensity was mild, median percentage of stained cells was 20% ± 14.24%, and median immunoreactive score (IRS) was 1. In PCA sections ( = 31), median IRS was 3, median staining intensity was strong, and median percentage of stained cells was 80% ± 16.46%. The mean SUV (±SD) of PCA (14.06 ± 15.56) was significantly higher than that of PN (2.43 ± 0.63; < 0.001). Receiver-operating-characteristic curve analyses of the SUV of PCA, validated by immunohistochemical staining in 62 tissue samples, showed the best cutoff to be 3.15 (sensitivity, 97%; specificity, 90%; area under curve, 0.987). Applied to multifocal PCA, it resulted in sensitivity and specificity of 87% and 97% respectively. The mean SUV of PCA and PN for an IRS of less than 2 ( = 26; 2.52 ± 0.64) was significantly lower than the mean SUV for an IRS of 2 or more ( = 36; 12.38 ± 15.02; < 0.001). The mean SUV was significantly lower in PCA samples with fewer than 50% stained cells ( = 30; 2.81 ± 2.35) than in samples with 50% or more ( = 32; 13.34 ± 15.55; < 0.001). There was no correlation between the SUV of PCA and Gleason score ( = 0.54). This study showed that SUV on Ga-PSMA PET/CT correlates significantly with PSMA expression in primary PCA, enabling the detection of PCA with a high sensitivity and specificity.

68Ga‐PSMA‐11 PET‐CT study in prostate cancer patients with biochemical recurrence and non‐contributive 18F‐Choline PET‐CT: Impact on therapeutic decision‐making and biomarker changes

“…Gauthé et al with an average serum PSA level lower than ours (2.8 ng/mL vs 4.11 ng/mL) had only 76% PSMA PET detection rate, probably due to a low PSA level . Nevertheless, our detection rate has been altered in the high PSA values by one of our patients, who had a negative PSMA PET‐CT while his PSA was 7 ng/mL but it reported that about 8% of PCa do not overexpress PSMA …”

“…Treatment changes and post-treatment PSA impact based on 68Ga-PSMA PET-CT results. BARBAUD ET AL.| 459 rate has been altered in the high PSA values by one of our patients, who had a negative PSMA PET-CT while his PSA was 7 ng/mL but it reported that about 8% of PCa do not overexpress PSMA 15.…”

Use of gallium‐68 prostate‐specific membrane antigen positron‐emission tomography for detecting lymph node metastases in primary and recurrent prostate cancer and location of recurrence after radical prostatectomy: an overview of the current literature

“…This is confirmed by the high efficacy of salvage radiotherapy (SRT) to the prostatic fossa in patients with a negative 68 Ga-PSMA PET result [36]. Failure to detect local recurrence is probably attributable to the inability to distinguish tumour activity from intense activity in the nearby bladder owing to urinary radiotracer excretion and to the fact that less aggressive PCa more often returns locally and less aggressive disease expresses less PSMA [46][47][48][49].…”

“…Most studies report a perpatient specificity of 90% or higher [10,11,13,[15][16][17]19]. This high specificity is a result of the high expression of PSMA in PCa and lymph node metastases, resulting in a high tumour to background ratio [46][47][48][49].…”

Detection Rate and Localization of Prostate Cancer Recurrence Using 68Ga-PSMA-11 PET/MRI in Patients with Low PSA Values ≤ 0.5 ng/mL

“…In analogy to our previous publication, only lesions highly suspected of being recurrence were considered positive: focal 68 Ga-PSMA-11 uptake in the soft tissue of the prostate bed, lymph nodes with an SUV max of at least 3 or pathologically increased size ($5 mm for perirectal nodes, $8 mm for iliac/retroperitoneal nodes, and $1 cm for inguinal nodes), focal bone uptake with correlating bone marrow replacement, or focal uptake with a correlating soft-tissue lesion (8). Most published series suggested an SUV max of 2-3 as an appropriate cutoff, especially for lymph nodes (10,11). To minimize false-positive interpretation of slightly PSMA-positive findings, a cutoff of 3 was selected.…”