An Australian experience using Tc-PSMA SPECT/CT in the primary diagnosis of prostate cancer and for staging at biochemical recurrence after local therapy

Background: Technetium 99 prostate-specific membrane antigen (Tc-PSMA) single-photon emission computed tomography/computed tomography (SPECT/CT) has the potential to provide greater accessibility globally than gallium 68 (Ga)-PSMA positron emission tomography (PET)/CT but has not been studied as extensively in primary diagnosis, staging, or relapse of prostate cancer (PC). We instituted a novel SPECT/CT reconstruction algorithm using Tc-PSMA and established a database to prospectively accumulate data on all patients referred with PC. This study extracts data on all patients referred over a 3.5-year period with the primary aim of comparing the diagnostic accuracy of Tc-PSMA and multiparametric magnetic resonance imaging (mpMRI) in the primary diagnosis of PC. The secondary aim was to assess the sensitivity of Tc-PSMA in detecting disease with relapse after either radical prostatectomy or primary radiotherapy. Methods: A total of 425 men referred for primary staging (PS) of PC and 172 men referred with biochemical relapse (BCR) were evaluated. We evaluated diagnostic accuracy and correlations between Tc-PSMA SPECT/CT, magnetic resonance imaging (MRI), prostate biopsy, prostate-specific antigen (PSA), and age in the PS group and positivity rates at different PSA levels in the BCR group. Results: Taking the biopsy's grade according to the International Society of Urological Pathology protocol as a reference, the sensitivity (true positive rate), specificity (true negative rate), accuracy (positive and negative predictive value), and precision (positive predictive value) for Tc-PSMA in the PS group were 99.7%, 83.3%, 99.4%, and 99.7%, respectively. Comparison rates for MRI in this group were 96.4%, 71.4%, 95.7%, and 99.1%. We found moderate correlations between Tc-PSMA uptake in the prostate and biopsy grade, the presence of metastases, and PSA. In BCR, the Tc-PSMA positive rates were 38.9%, 53.2%, 62.5%, and 84.6% at PSA levels of <0.2, 0.2 to <0.5, 0.5 to <1.0, and > 1.0 ng/mL respectively. Conclusions: We have shown that Tc-PSMA SPECT/CT using an enhanced reconstruction algorithm has a diagnostic performance similar to Ga-PSMA PET/CT and mpMRI in an everyday clinical setting. It may have some advantages in cost, sensitivity for primary lesion detection, and the ability for intraoperative localization of lymph nodes.