Proposed Criteria Positions PSMA PET for the Future

Prostate cancer is an oncologic disease that has been deprived of the benefits of molecular imaging in this era of oncologic 18FFDG PET/CT compared with other tumor types due to its inherent biologic predilection for fatty acid rather than glucose metabolism. Because of this unmet clinical need, there has been an increased interest and development of emerging non–18F-FDG PET radiotracers for prostate cancer including choline (11C-choline, 18F-fluorocholine, 18F-fluoromethylcholine), acetate (11C-acetate, 18F-fluoroacetate), and amino acid–based (18F-fluciclovine) agents. Some of these radiotracers have successfully received U.S. Food and Drug Administration New Drug Application approval for clinical use (11C-choline, 18F-fluciclovine), which has been well received. However, recent developments and promising initial clinical studies with novel 18Fand 68Ga-labeled low-molecularweight prostate-specific membrane antigen (PSMA) PET radiotracers have generated increased excitement because of their very promising early results for improved detection and staging of prostate cancer beyond conventional imaging modalities and even other non-18F-FDG PET radiotracers (2,3). However, these new PSMA PET radiotracers will need to deliver on this initial promise in the next phase of their development for it to become a valuable tool for patient management and drug development for prostate cancer in forthcoming systematic multicenter clinical trials. The authors of 2 new proposed PSMA PET criteria to facilitate prostate cancer reporting and classification make important and needed first steps in the next phase of development of this class of molecular imaging agents for prostate cancer, also applicable to other non-PSMA PET agents (4,5). PSMA is a viable target for prostate cancer imaging because of its high expression on most prostate cancer cells and association with more aggressive prostate cancer biology (3). The clinical relevance of PSMA PET for prostate cancer imaging includes a high signal-to-background signal for improved tumor detection, especially but not limited to, localization of the sites of biochemical recurrence compared with conventional imaging and even to choline PET at low serum prostate-specific antigen levels (6,7). Despite this high performance, false-positive lesions have been reported and these pitfalls, including PSMA PET uptake in normal physiologic distribution (e.g., ureter, sympathetic chain ganglion), inflammatory processes (e.g., sarcoidosis), benign osseous processes (e.g., Paget’s disease), and tumor neovasculature of nonprostate malignancies (e.g., renal cell carcinoma), need to be taken into consideration in future criteria (8). A standardized reporting system for incorporation of PSMA PET imaging to meet upcoming clinical diagnostic and clinical research needs requires an efficient but accurate method to meet the needs for the imager, referring treating clinicians, and multicenter clinical trials. These clinical and research needs, while overlapping, have unique requirements. Clinical diagnostic reporting tools need to be simple, efficient, and clinical action–directed, while adaptable to unique clinical situations. Incorporation of PSMA PET findings into current anatomic imaging–based diagnosis staging criteria is also needed to efficiently communicate these findings to support clinician therapeutic management decisions. Research reporting tools need to be reproducible and accurately allow for stratification of patient cohorts as well as provide the structure for pooling of patient data for multicenter trials. Both reporting tools need to be adaptable to allow for incorporation of updates and changes as we learn more about PSMA PET imaging with new research findings and clinical experience. The Reporting and Data System (RADS) is a quality assurance tool applied to pretherapy initial diagnosis of primary prostate cancer. The tumor, node, and metastasis (TNM) classification of malignant tumors is a notation system that describes the stage and anatomic extent of a solid tumor. Both PSMA-RADS and PROMISE classifications propose incorporation of PSMA PET into existing systems of tumor diagnosis and staging classifications, albeit with complementary proposals based on the RADS and TNM classification, respectively. PSMA-RADS version 1.0 proposes a standardized method to “allow for an accurate and efficient means of relaying findings to referring providers” and “facilitate the collection of data for large prospective trials” (4). It proposes reporting an imager’s level of certainty regarding PSMA PET findings using a 5-point scale (ranging from PSMA-RADS-1, benign; PSMA-RADS-2, likely benign; PSMA-RADS-3, equivocal; PSMA-RADS-4, prostate cancer highly likely; PSMA-RADS-5, prostate cancer almost certainly present), with additional sublevels for each category. PSMA-RADS is proposed for categorization of findings outside the prostate in pelvic or distant metastatic disease and does not address primary prostate cancer. An individual lesionand patient-based PSMA-RADS report is also proposed, an important perspective requiring simplification of complex imaging findings in patients with widespread metastatic disease. A strength of this proposed method is the incorporation of clearly defined levels of confidence in imaging Received Nov. 23, 2017; revision accepted Dec. 14, 2017. For correspondence or reprints contact: Steve Y. Cho, University of Wisconsin School of Medicine and Public Health, WIMR1, Rm. 7139, 1111 Highland Ave., Madison, WI 53705. E-mail: scho@uwhealth.org Published online Jan. 4, 2018. COPYRIGHT© 2018 by the Society of Nuclear Medicine and Molecular Imaging. DOI: 10.2967/jnumed.117. 204057