Background: Standard imaging in early stage PC has focused on detecting metastases (mets) within the abdomen and pelvis. The incidence of IT mets (lung, mediastinal, or supraclavicular) mets is unknown, but presumed to be negligible. Whole body ⁶⁸Ga-PSMA PET has greater sensitivity compared to conventional imaging, affording the opportunity to estimate the incidence of IT mets. Methods: Newly diagnosed or biochemically recurrent (BCR) PC patients (pts) with apparent localized disease on standard imaging were enrolled on a prospective study of ⁶⁸Ga-PSMA PET imaging between June 2015 and January 2017 and were analyzed for incidence of IT mets. Positive lesions were defined as uptake higher than blood pool. When appropriate, patients underwent confirmatory biopsy of the PSMA-avid IT lesions. Results: 364 pts underwent ⁶⁸Ga-PSMA PET imaging, including 121 (33%) pts with newly diagnosed PC and 243 (67%) pts with BCR. 145 pts (40%) had at least 1 PSMA-avid metastasis. PSMA-avid IT mets were detected in 20 pts (5.5% of overall cohort; 13.8% of those with ≥ 1 PET-positive mets), including 3 newly diagnosed (2.5%) pts and 17 (7.0%) pts with BCR. 9 of 20 pts (45%) had IT mets as the only detectable site of metastasis on PET. Biopsy of the PSMA-avid IT lesion was found to harbor PC in 5/5 patients (100%). Sites of detection included: supraclavicular node, n = 9 (2.5%); mediastinal node(s), n = 10 (3.6%), and visceral lung, n = 4 (1.0%). In the entire study cohort of 364 pts, 43% of pts had a Gleason Score ≥ 8 at diagnosis, median PSA was 4.87 ng/mL (range: 0.04 – 83.7), and the median PSA doubling time was 6.2 months (range: 0.4 – 78.3) in patients with BCR. There were no significant differences in PSA, PSA doubling time, Gleason grade, or stage between patients harboring IT metastases vs. those who did not. Conclusions: IT mets are detected by ⁶⁸Ga-PSMA PET imaging at an appreciable frequency in early stage PC with apparent localized disease by conventional imaging, which may significantly impact management in these cases. Further studies are warranted to validate these findings and determine the optimal strategy for the detection and treatment of supradiaphragmatic metastases in newly diagnosed and biochemically recurrent PC. Clinical trial information: NCT02918357