Potentials of 68Ga-prostate specific membrane antigen PET/CT for primary diagnosis of prostate cancer

INTRODUCTION AND OBJECTIVES: The current study is designed to test the hypothesis that prostate biopsy using 68Ga-PSMA PET/Trans Rectal Ultrasound (TRUS) fusion images may have a clinical impact in the subset of patients with a high suspicion of prostate cancer (PCa), a previously negative biopsy and contraindications to or negative multiparametric MRI (mpMRI). METHODS: This prospective study was performed at a tertiary high volume Hospital in order to use 68Ga-PSMA PET/CT in a selected subgroup of patients for diagnosis of primary PCa: men with persistently elevated PSA and/or PHI (prostate health index) suspicious for PCa, negative digital rectal examination, and at least one negative biopsy (Protocol ICH: MpMRI new-1_2018_emended). The cohort comprised patients with either an equivocal mpMRI (PIRADS v2. 2) or an absolute or relative contraindication to mpMRI. All patients underwent whole body 68Ga-PSMA PET/CT 60 minutes after radiopharmaceutical injection (185-250MBq). Focal PSMA uptake superior to background activity was considered for the analysis and outlined for target biopsy. Semi-quantitative measures for all lesions comprised SUVmax and SUVratio-to-background. Sensitivities, specificities, and accuracy were calculated compared to histopathology results. RESULTS: Overall, 88 cases were referred to 68Ga-PSMA PET/CT: 66 patients (75%) had already performed mpMRI with either a negative result for PCa (n[28) or positive mpMRI but negative biopsy. In this subset of patients, 54 cases (61%) were addressed to 68GaPSMA PET/TRUS fusion biopsy that demonstrated the presence of 33 malignant lesions: 14 cases with GS 6 (3þ3), 19 cases with GS 7 (15 cases GS 3þ4; 4 cases GS 4þ3), and 2 cases GS 10 (5þ5). Mean SUVmax and SUVratio-to-background for PCa lesions resulted statistically significantly higher than in benign lesions (P < 0,001). ROC analysis performed for optimal cut-off points demonstrated that a SUVmax >5.4 and a SUVratio >2.2 could identify clinically significant PCa (GS 7) with an accuracy of 85.9% and 91.5%, respectively. In the subset of patients who had already performed mpMRI, we found instead no correlation between PIRADS and lesions GS, SUVmax or SUVratio-to-background. CONCLUSIONS: Our study confirms and expands previous preliminary findings. In patients with a high suspicion of cancer, despite previously negative biopsy and/or mpMRI, 68Ga-PSMA PET/CT is capable to detect malignant lesions and identify with a high sensitivity clinically relevant PCa.