Why targeting PSMA is a game changer in the management of prostate cancer - a Urologist's point of view.

Prostate-specific membrane antigen (PSMA), is a transmembrane glycoprotein that is highly expressed on prostate adenocarcinomas, exhibits only limited expression in benign and extra-prostatic tissues, and thus represents an ideal target for the diagnosis and management of prostate cancer. Since its discovery over 30 years ago, significant effort has been made to develop clinical technology targeting PSMA. The last 5 years have seen an explosion of development of new agents targeting PSMA for diagnostic and therapeutic use. Imaging agents targeting PSMA have been developed for single photon emission computed tomography (SPECT) and positron emission tomography (PET) imaging platforms. PSMA PET imaging appears to outperform traditional imaging in the high risk localized disease state, in patients with biochemical recurrence following treatment, and in advanced disease. To date, the majority of reported clinical studies of therapeutic agents utilize PSMA-targeted radiometals to deliver beta radiation to metastatic disease sites, with Lutetium-177 being the most widely-investigated therapeutic radio-isotope. Studies of both antibodies and small molecule agents have been published and have demonstrated encouraging results. Safety appears generally limited to mild transient bone-marrow toxicity and xerostomia owing to uptake of the small molecule agents in the salivary glands. Radiologic responses can be dramatic and decreases in pain have been observed. The effect on overall survival, however, has yet to be demonstrated.

Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 2017 Oct 06 [Epub ahead of print]

Nicholas M Donin, Robert Reiter

David Geffen School of Medicine at UCLA, United States.