68Ga-PSMA11 PET/CT localizes recurrent prostate cancer with high accuracy: preliminary results from a phase 2/3 prospective trial

456 Objectives: 68Ga-PSMA11 PET/CT provides improved localization of biochemically recurrent prostate cancer. For approval and reimbursement, accuracy needs to be established in a prospective study employing independent lesion validation. Methods: In this phase 2/3 prospective trial (NCT02940262), patients with biochemically recurrent prostate cancer after primary prostatectomy (n=205) or radiation therapy (n=45) underwent 68Ga-PSMA11 PET/CT. Presence of prostate cancer was recorded on a patient and region base. Regions were prostate bed, pelvis, extra-pelvic, and bone. Lesions were validated in 51% of PET/CT-positive patients by histopathology (n=33), imaging (n=62) and/or PSA after targeted radiation therapy (n=9 patients). PSA response after 68Ga-PSMA11 PET/CT guided focal salvage therapy (surgery/radiotherapy) was recorded in 23 of 25 patients (8% drop out). Endpoints were positive predictive value (PPV), detection rate and outcome. Results: PPV validated by histopathology was 85% on a patient base (primary endpoint). PPV as determined by any type of validation was 89% on a patient and 91% on a region base. 68Ga-PSMA11 PET/CT localized recurrent prostate cancer in 197 of 250 (79%) patients; stratified by PSA: 41% for <0.5 ng/ml (n=54), 66% for 0.5 to <1.0 ng/ml (n=38), 86% for 1.0 to <2.0 ng/ml (n=36), 96% for 2.0 to <5.0 ng/ml (n=55), and 99% for ≥5.0 ng/ml (n=67). Lesion location was in 35% prostate bed, 61% pelvis, 35% extra-pelvic, and 31% bone. Following focal salvage therapy alone, 18 (78%) patients had a PSA drop of 50% or more, 7 (30%) patients had biochemical complete response (PSA undetectable). Conclusions: Using an independent reference standard, we establish high 68Ga-PSMA11 PET/CT PPV for localization of recurrent prostate cancer. PET/CT guided salvage therapy resulted in high biochemical response rates. Pooled multicenter findings will be submitted for a New Drug Application.