GU Oncology Now recently spoke with Amar U. Kishan, MD, Associate Professor, Chief of Genitourinary Oncology Service, Vice Chair of Clinical and Translational Research, Department of Radiation Oncology, University of California, Los Angeles.
Dr. Kishan spoke to us about the profound impact precision medicine has on the treatment of advanced prostate cancer, the use of phenotypic biomarkers in prostate cancer, and the game-changer that is PSMA-directed imaging. See what Dr. Kishan had to say.

GU Oncology Now: Can you provide us with some background on yourself and your specialty?

Amar U. Kishan, MD: Sure. So I’m an Associate Professor of Radiation Oncology at the University of California, Los Angeles where I serve as the Vice Chair of Clinical and Translational Research. I treat GU cancers, so mainly cancers of the prostate and bladder.

GU Oncology Now: How big an impact has precision medicine had on prostate cancer?

Amar U. Kishan, MD: I think it’s had a huge impact, but it has much more promise to do great things in the future. And so I think we can draw an analogy to something like breast cancer, which is a highly common cancer as well, but I think precision medicine is a little bit ahead of us there. So for example, there are biomarkers for the guidance of therapies that have been introduced for far longer in the breast cancer world than in the prostate cancer world. But I would add that there’s different types of precision. So there’s kind of like physical precision when it comes to precise radiation, that’s more related to my field, imaging precision, and then there’s kind of what we usually think about. Let me say of medicine is molecular precision or genomic precision.

GU Oncology Now: What are some advantages (and challenges) of using phenotypic biomarkers in advanced prostate cancer?

Amar U. Kishan, MD: So, coming from the context of a radiation oncologist, so our involvement in advanced prostate cancer kind of like metastatic prostate cancer is often in the realm of what we call Oligometastatic disease. Essentially, if a patient has a recurrence of their prostate cancer and it appears that it’s actually metastasized, but only to a few locations, there’s an emerging role for what we call metastasis directive therapy, where we treat these metastatic sites with ablative doses of radiation. So that’s kind of one major indication. And the other is in someone that has metastatic disease, but it appears to be what we would call low volume, or also maybe parallel to this Oligometastatic definition. It’s only spent a few spaces, there’s a role to treat the prostate itself with radiation. The challenge is there can be different things that lead to someone having what we call Oligometastatic disease or low volume disease.

It might be that we are catching things early and we are only seeing a few spots, but there’s actually more things brewing. And in which case it’s kind of a false suppression of limited disease, or, it could be that’s actually, it, this is actually the extent of the disease. And I think where phenotypic and predictive prismatic biomarkers would be helpful is allowing us to distinguish those two possibilities. So for instance, if I have a patient that has five lesions on their scan and we’re considering treating those lesions, it would be very important to me and to the patient to know, is this a high likelihood of being all that is that we need to treat and potentially offering this person like a long interval of being free from other therapies, or do they have a very biologically or genetically aggressive cancer? And really what we’re seeing is the tip of the iceberg. I think that would be very important for us to know. Right now we don’t have actionable markers that gives us those answers.

GU Oncology Now: What are the main advantages of using PSMA-directed modalities in prostate cancer?

Amar U. Kishan, MD: So PSMA has been a game changer in many ways. It has a incredibly high sensitivity compared to conventional imaging, meaning it’s able to pick up disease for instance, outside the prostate and someone that’s newly diagnosed with prostate cancer in a fair number of cases and in some, and as a recurrence of prostate cancer, after for example, surgery may be able to help us define, for example, our treatment fields. This has been revolutionary in the sense that it allows us to in the postoperative setting where it’s been studied the most better tailor our treatments. For example, if someone is showing up and they have a rising PSA after radical prostatectomy, and we’re thinking about treating their prostate bed, but we get a PSMA scan and it shows there’s a node that’s positive, that’s very important to know because we might not have included that area on our treatment field.

We exactly the patient to treatment that missed the area that we know that they have cancer in. You know, it could be true that the PSMA scan, isn’t telling the whole story in that example of a patient that has a node lighting up on PSMA, that doesn’t mean there’s no disease elsewhere. That doesn’t mean there’s nothing microscopic in the prostate bed, but because false positives with PSMA are relatively low, it means there is definitely something in that lymph node. And so if to us, that’s an unprecedented ability to change our radiation fields. In the setting of someone with intact prostate cancer, for example, someone that has aggressive prostate cancer, there’s overall about a 24% chance that we might see something outside of prostate on a PSMA scan.

And that too would be important for us to take into account in the same analogous example, if a lymph node was positive, we would want to account for that in our treatment plan. Where the danger might come in as if we deprive a patient of what would otherwise have been a standard therapy, just because we see something on a PSMA scan, for example, the patient that had otherwise highly curable disease, we get a scan and maybe there’s one spot in a bone nearby.

Do we want to totally change our plan just because of one spot in the bone with this new imaging test, probably not; that might not be appropriate, but at the same time, we do want to take into account that we saw something in the bone that we think is real when we’re formulating a treatment plan for this patient.

GU Oncology Now: What are some innovations that could potentially shape the future of prostate cancer care?

Amar U. Kishan, MD: So I think developing prognostic and predictive biomarkers will be transformative in the localized prostate cancer space. So for example, when we’re treating patients with prostate cancer with radiation, we often times add a hormone therapy to the mix to improve the effectiveness of our treatment, but our definitions of what’s an aggressive prostate cancer, and what’s a non-aggressive prostate cancer are based off of studies done in the 1990s. And so having a new tool to be able to tell us, well, this pace max has a biological aggressive cancer, we need to add hormone therapy for a long period of time in order to include their outcomes will be very helpful.

Conversely, if someone has what we thought was aggressive disease, but we’re able to biologically, so it’s not aggressive and we can swerve in or eliminate the hormone therapy that would have a lot of quality of life impacts for that particular patient. Another thing that I think will be transformative is maybe a combination of some of these new PSMA based radionuclide therapies like the Lutetium 177 PSMA therapy, perhaps in combination with targeted radiation, for the example of a patient that has a couple of spots of disease on a PSMA pack. Perhaps we can treat those isolated spots with high dose radiation therapy, but also add something like Lutetium 177 in case there’s any microscopic disease that we couldn’t target with our radiation.

GU Oncology Now: Any closing thoughts?

Amar U. Kishan, MD: I think these new imaging tools are highly useful for prostate cancer and are really going to change the way that we approach treatment and allow us to personalize things in a way that we haven’t been able to do before.