A comprehensive assessment of 68Ga-PSMA-11 PET in biochemically recurrent prostate cancer: Results from a prospective multi-center study in 2005 patients.

We prospectively investigated the performance of the prostate-specific membrane antigen (PSMA) ligand 68Ga-PSMA-11 for detecting prostate adenocarcinoma in patients with elevated prostate-specific-antigen (PSA) after initial therapy. Methods: 68Ga-PSMA-11 hybrid positron emission tomography (PET) was performed in 2005 patients at the time of biochemical recurrent prostate cancer (BCR) following either radical prostatectomy (RP) (50.8 %), definitive radiation therapy (RT) (19.7 %), or RP with post-operative RT (PORT) (29.6 %). Presence of prostate cancer was assessed qualitatively (detection rate = positivity rate) and quantitatively on a per-patient and per-region basis creating a disease burden estimate from presence or absence of local (prostate/prostate bed), nodal (N1: pelvis) and distant metastatic (M1: distant soft tissue and bone) disease. The primary study endpoint was the positive predictive value (PPV) of 68Ga-PSMA-11 PET/CT confirmed by histopathology. Results: Following prostatectomy, the scan detection rate increased significantly with rising PSA levels (44.8 % at PSA < 0.25 to 96.2 % at PSA > 10 ng/mL; P < 0.001). The detection rate significantly increased with rising PSA levels in each individual region, overall disease burden, prior androgen deprivation, clinical T-stage, and Gleason grading from prostatectomy specimen (P < 0.001). Following RT, the detection rate for in-gland prostate recurrence was 64.0 % compared to 20.6 % prostate bed recurrences after RP and 13.3 % following PORT. PSMA-positive pelvic nodal disease was detected in 42.7 % following RP, in 40.8 % after PORT and 38.8 % after RT. In patients with histopathologic validation the PPV per-patient was 0.82 (146/179). The SUVmax of histologically proven true positive lesions was significantly higher than false positive lesions (median 11.0 (IQR 6.3 - 22.2) vs 5.1 (IQR 2.2 - 7.4) P < 0.001). Conclusion: We confirmed a high PPV of 68Ga-PSMA-11 PET in BCR and the PSA level as the main predictor of scan positivity.