(UroToday.com) The second session of the Advanced Prostate Cancer Consensus Conference 2021 which was hosted virtually in the context of the COVID-19 pandemic focused on the role of prostate specific membrane antigen (PSMA) imaging in prostate cancer diagnostics and therapy. Following a background presentation from Dr. Derya Tilki, Dr. Stefano Fanti discussed potential pitfalls of different PSMA-based radiotracers.
He began by emphasizing that there are technical issues, general PSMA pitfalls, specific PSMA limitations, and the effects of interpretation that affect the clinical utility of PSMA-imaging.
Dr. Fanti emphasized that there are new technical procedural guidelines regarding PSMA imaging that are due to be published next year. However, already there is evidence that PSMA is relatively widely available worldwide with evidence that the imaging is reproducible with consistent results worldwide.
However, he emphasized that no imaging approach will have 100% sensitivity. Based on evidence from systematic reviews and meta-analysis, even in best indication for PSMA imaging among patients with biochemical recurrence following local therapy and among patients with high PSA values, the sensitivity of PSMA is unlikely to exceed 95%. Further, despite the name, PSMA is not prostate cancer specific. As a result, there may be “false positive oncologic results” as a result of lung cancer, colon cancer, and lymphoma. Further, a number of non-malignant conditions may also cause PSMA false positives. These include Crohn’s disease and COVID-19.
While the concept of “PSMA-based imaging” is a basket concept, Dr. Fanti highlighted that there are specific differences between tracers, of which there are many.
Dr. Fanti first highlighted an anecdotal comparison of C-11 choline PET/CT and 68Ga-PSMA-11 PET/CT to emphasize the much higher sensitivity of the PSMA-based imaging approach. Assessing a similar question more systematically, he presented data from Dr. Calais from a prospective, single-center, comparison of 18F-fluciclovine PET/CT and 68-Ga-PSMA-11 PET/CT among patients with early biochemical recurrence following prostatectomy. In this analysis, 68-Ga-PSMA-11 had significantly higher detection rates.
In contrast to these comparisons of PSMA-based imaging and other PET modalities, less is known about the comparison between PSMA based tracers. Dr. Fanti emphasized that all approaches have essentially same image quality. In a comparison between 18F-DCFPyL and 68-Ga-PSMA, results were essentially comparable across a number of studies. However, a comparison of 68-Ga-PSMA-11 and 18F-PSMA-1007 demonstrated a much higher rate of PSMA-avid lesions on 18F-PSMA-1007 which could be attributed to benign findings. Thus, the specificity and positive predictive value of this approach may be lower.
Dr. Fanti further suggested that 68Ga-PSMA-11 and DCFPyL may be preferable to 18F-PSMA-1007 with respect to characterization of bony findings. In contrast, 18F-PSMA-1007 may be preferable in the detection of small loco-regional recurrences. Integrating this data, he suggested that there are no robust data to guide choice of agent and thus, it depends on local experience and opinion though, in his group, they favour 68Ga-PSMA-11.
Moving beyond technical aspects of imaging, interpretation and reporting are critical. Dr. Fanti emphasized the importance of specialization and training for nuclear medicine physicians interpreting these studies. This is particularly important in understanding and interpreting equivocal findings. For example, he highlighted those solitary faint findings in rib are often non-malignant; however, not all rib findings are non-pathologic and an understanding of both imaging considerations and clinical context can help adjudicate these.
Further, Dr. Fanti emphasized that both patient and referring clinician expectations regarding clinically actionable results from PSMA testing are high as PSMA is quite widely seen as the “best” imaging modality for prostate cancer available and it is widely recommended for evaluation of patients with recurrent disease and increasingly utilized in upfront staging. While he described PSMA-based imaging as a “game changer”, he cautioned that “with great power comes great responsibility”. To this end, he emphasized the importance for nuclear medicine physicians to obtain the appropriate expertise to interpret these studies. However, he cautioned treating and referring clinicians that we must obtain and act on the results of novel imaging techniques appropriately.
Presented by: Stefano Fanti, MD, Professor, Department of Experimental, Diagnostic and Specialty Medicine - DIMES, Director of Nuclear Medicine Division of the PET Unit, Director of Speciality School of Nuclear Medicine, University of Bologna, Bologna, Italy.Written by: Christopher J.D. Wallis, University of Toronto, Twitter: @WallisCJD during the 2021 Advanced Prostate Cancer Consensus Conference, Saturday, October 9, 2021.