A Comprehensive Assessment of <sup>68</sup>Ga-PSMA-11 PET in Biochemically Recurrent Prostate Cancer: Results from a Prospective Multicenter Study on 2,005 Patients
Monica Abghari-Gerst, Wesley R. Armstrong, Kathleen Nguyen, Jérémie Calais, Johannes Czernin, David W. Lin, Namasvi Jariwala, Melissa E. Rodnick, Thomas A. Hope, Jason W.D. Hearn, Jeffrey S. Montgomery, Ajjai Alva, Zachery R. Reichert, Daniel E. Spratt, Timothy D. Johnson, Peter J. H. Scott, Morand Piert
Abstract
We prospectively investigated the performance of the prostate-specific membrane antigen (PSMA) ligand <sup>68</sup>Ga-PSMA-11 for detecting prostate adenocarcinoma in patients with elevated prostate-specific-antigen (PSA) after initial therapy. <b>Methods:</b><sup>68</sup>Ga-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 <sup>68</sup>Ga-PSMA-11 PET/CT confirmed by histopathology. <b>Results:</b> 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; <i>P</i> < 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 (<i>P</i> < 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 SUV<sub>max</sub> 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) <i>P</i> < 0.001). <b>Conclusion:</b> We confirmed a high PPV of <sup>68</sup>Ga-PSMA-11 PET in BCR and the PSA level as the main predictor of scan positivity.