Targeting PSMA in Advanced Prostate Cancer - Episode 5

What is a Phenotypic Biomarker?

April 13, 2021
Ulka Vaishampayan, MD

,
Oliver Sartor, MD

Oliver Sartor, MD, discusses the use of phenotypic biomarkers such as prostate-specific membrane antigen (PSMA), and how these biomarkers can be utilized for prediction of prognosis as well as responsiveness to therapy.

Oliver Sartor, MD: We need to move on to talk about some phenotypic markers as opposed to genetic markers. This is a bit of a new concept, but biomarkers really help us understand a couple of things. Biomarkers can be prognostic or they can be predictive. When they’re predictive, they’re used in terms of selecting therapies and have a differential effect.

We have phenotypic biomarkers, particularly image-based biomarkers, that help us choose therapies and hopefully be able to find patients who will respond. I’ll give an obvious and old example of this: a bone scan. A bone scan is actually a phenotypic marker. If you have a bone scan that is positive, you may have a patient who would be a candidate for radium because you have a bone-targeted therapy. 

Now we have new and interesting things like PSMA [prostate-specific membrane antigen]. Now that we are developing PSMA-targeted therapies, it makes a lot of sense to think about PSMA image in terms of selecting those patients. If they don’t have PSMA positivity, you probably want to treat with a PSMA-targeted molecule, so this is going to reverberate not only through the radiopharmaceuticals but also in potentially some of the newer BiTE [bispecific T-cell engager] molecules, the immunotherapy, instead of targeting PSMA.

The idea of a phenotypic biomarker is something you’re going to hear much more about in the coming months and years. It’s pretty simple. It just means what you detect on the cell, nongenomic, will help us predict either prognosis or the responsiveness to therapy. We’re going to have a whole bunch more other than PSMA. We’re going to have a whole series of image-based biomarkers that are novel, based on the entire remarkable nuclear medicine conferences that are ongoing where all these new data and biomarkers are being presented. It’s quite interesting.

Ulka N. Vaishampayan, MD: Why do you think PSMA is such a useful phenotypic marker?

Oliver Sartor, MD: There are a couple of reasons why. No. 1 is that it’s highly overexpressed in aggressive cancer, probably even more upregulated in the context of cancers that have been hormonally treated. Maybe even enzalutamide will cause a little more upregulation. It’s present in the majority of patients, so it’s not like a rare patient. You can actually visualize the PSMA with the PET [positron emission tomography] imaging, either with PSMA-11 gallium-68 or maybe the DCFPyL with a F-18 [fluoroethyltyrsine] marker. We have the ability to image with it. We can treat with it. That image-treated approach is called a theranostic approach, which is going to be very valuable. 

PSMA, because it’s been linked to the imaging as well as the treatment, has an inherent advantage because we can immediately translate what we see into what we treat. A couple of advantages to PSMA: the natural overexpression in aggressive disease, so the majority of patients expressing it, and the targetability of this particular protein on the cell surface.

Ulka N. Vaishampayan, MD: I agree. The 80% of our patients with prostate cancer expressed are likely to have PSMA expression. You can benefit much more compared with genomic biomarkers, where you are selecting 5% to 20% of the patients, depending on which genomic marker you use. It makes the treatment widely applicable.

This transcript was edited for clarity.