Prostate cancer is the most common cancer in men in the United States.1 While the overall prognosis of men diagnosed with prostate cancer is excellent, prostate cancer is also the second leading cause of cancer-related mortality in men in the United States, as a large subset of patients will have progressive disease to which they will ultimately succumb.1 There is a wide range of treatment options for prostate cancer, ranging from watchful waiting to systemic chemotherapy and accurate evaluation of the extent of disease by imaging is essential for prognostication and guiding treatment decisions. Traditionally, prostate cancer imaging has relied on bone scans and whole body CTs to assess for distant disease; however, this strategy has been hampered by the relatively low sensitivity of these studies.

Recently, the introduction of multiple prostate-specific membrane antigen (PSMA)-targeted PET agents has revolutionized prostate cancer imaging. These agents bind to PSMA, a transmembrane protein that is highly expressed in prostate cancer and has been linked with folate metabolism. PSMA PET agents have demonstrated superior sensitivity and specificity relative to other prostate imaging modalities in several landmark clinical trials. Accordingly, updated prostate cancer guidelines now recommend PSMA PET/CT as the front-line imaging modality for initial staging of unfavorable intermediate, high, or high-risk prostate cancer, the evaluation of biochemically recurrent disease, to evaluate progressive disease and eligibility for PSMA radioligand therapy.2,3 This has led to a rapid increase in the number of PSMA studies performed and the number of physicians called on to interpret these studies.

Despite the name, PSMA is not exclusive to prostate cancer, but instead, is expressed in a range of different structures and lesions, both physiologic and pathologic.4,5 This and other factors can lead to findings on PSMA PET studies that can mislead the new interpreter. We hope this manuscript will serve to introduce the reader to the pitfalls commonly encountered in PSMA PET interpretation.