PSMA-Targeted Radioligand Therapies in Advanced Prostate Cancer - Episode 1

PSMA as a Biomarker in Advanced Prostate Cancer

Dr Scott T. Tagawa describes what prostate-specific membrane antigen (PSMA) is and explains its evolving role as a diagnostic, prognostic and therapeutic target in patients with advanced prostate cancer.

Scott T. Tagawa, MD, MS, FACP: Hi. My name is Scott Tagawa. I am a medical oncologist at Weill Cornell Medicine, NewYork-Presbyterian–Weill Cornell Medical Center, in New York City.

Prostate-specific membrane antigen (PSMA) is a cell-surface protein that is widely expressed on most prostate cancer cells. It is indirectly related to the androgen receptor (AR). Generally speaking, when a tumor has the AR, PSMA is usually there. Not in 100% [of cases], but in the vast majority of prostate cancer cells—whether they are in the prostate [or] in metastases and whether they are non-castrate, castration-sensitive, or castration-resistant. There is a general relationship between advanced grade, stage, and castration resistance—that is, having more PSMA present.

PSMA can be measured via liquid biopsy, specifically for tumor cells, as well as imaging. One important factor in terms of imaging is volume. An individual tumor might have a lot of cells with a lot of PSMA expression that may be missed on imaging if it is very small.

PSMA is a useful target both diagnostically and therapeutically, because it is usually very highly expressed. It is there approximately 90% of the time. Diagnostically, it is a very useful agent because of its prevalence and high level of expression. As a cell-surface target, it lends itself to imaging modalities. [We can now use] various PSMA PET [positron emission tomography] tracers, [which] are much more sensitive and specific than we have had with any imaging modality in the past, including cross-sectional imaging with CT [computed tomography], MRI [magnetic resonance imaging], bone scintigraphy, and even PET tracers (eg, choline C 11 or fluciclovine F 18). PSMA is also a good therapeutic target, because it is almost always there. Because most of our therapies target the AR pathway, most subsequent tumors (ie, AR-resistant tumors) generally have a higher level of PSMA expression. That lends itself to targeting, as we have different types of vehicles—small molecules, minibodies, and full-length antibodies—that can target PSMA. We have 3 categories of therapeutics that are in the clinic now, and some are poised, hopefully, for approval [by the US Food and Drug Administration] relatively soon. Those include oximes (or drugs), immunotherapy agents (eg, CAR [chimeric antigen receptor] T cells or biospecifics), and targeted radionuclides.

There is 1 little difference between PSA [prostate-specific antigen] and PSMA, and that is the membrane. As I tell patients, PSA is made inside cells, is secreted into the blood, and is a useful circulating biomarker. PSMA is stuck to the cell surface. It does not leave the cell and does not circulate unless that entire cell is circulating (eg, as with a circulating tumor cell). Therefore, it is a useful cell surface target, both diagnostically as well as therapeutically, because it is not floating around free in the blood. It is stuck to a cell and can be used for imaging as well as treatment.