Robert Flavell: Thank you for joining me today for this special patient-centered educational video from the Society of Nuclear Medicine and Molecular Imaging. My name is Robert Flavell. I'm an Assistant Professor and the Chief of Molecular Imaging and Therapeutics at the University of California in San Francisco. And today I'm going to present a lecture on prostate cancer, diagnosis, and treatment. And the focus of today's video is on PSMA PET imaging. This is a very exciting, new, and evolving area in our field. And I think this is a new method that is really helping prostate cancer patients worldwide.

In this session, we're going to cover the basics of the use of imaging and cancer and comparing structural versus functional imaging. We're going to talk about how PSMA PET is used in diagnosing prostate cancer, and then we're going to go over a case study of PSMA PET to show how it can help individual patients.

Imaging is used as part of all cancer care, but particularly so in prostate cancer, and within imaging, nuclear medicine is an integral part of modern patient care. In no area is it more important than prostate cancer, and importantly, imaging allows us to see inside the body detecting abnormalities, underlying symptoms, and diseases, and lets us monitor responses to new therapies for treating the cancer.

Imaging has been used for a long time in cancer, and in fact, since the 1920s, chest x-rays and x-ray based methods have been used for seeing inside the human body. And you can see here on the left side of the screen an example of a chest x-ray demonstrating lung masses in that patient with cancer. More recently, techniques such as CT computed tomography, and MRI or magnetic resonance imaging allows us to get even greater anatomical resolution. So you can see here on this CT scan in the patient's right lung, we can see a mass corresponding to something similar that you might've seen on that old 1920s chest x-ray.

But all of these methods that I just mentioned have some features in common, specifically that they see alterations in tissue structure. However, in some cases changes in metabolism or tissue function actually come before gross alterations in tissue structure, and therefore, functional imaging using methods such as PET, or positron emission tomography, could be more sensitive for detecting cancer and following response to treatment.

So here's a comparison of structural versus functional imaging. On the left side of that screen that chest x-ray I showed you, and on the right side of the screen, a PET scan showing functional imaging. You'll notice looking at this PET scan that a lot of the normal organs that we expect to see, like the heart, are missing. That's because the PET scan specifically works to tell us about the function of the normal tissues. And in this case, the expression of the PSMA antigen, which is specific for prostate cancer.

In prostate cancer, imaging is commonly used and probably the two most common modalities are CT scan of the chest, abdomen, and pelvis and magnetic resonance imaging or MRI, usually of the prostate gland itself. Functional imaging of course also plays an important role. And the real classic method for this is called a bone scan, which is used to look for sites of spread of prostate cancer to the skeleton. More recently, next-generation imaging, including positron emission tomography, or PET imaging with next-generation agents, such as F18-fluciclovine, which is also called Axumin®, or PSMA based agents also called prostate-specific membrane antigen. These agents have really increased the sensitivity for detecting sites of prostate cancer and are helping to change the face of modern prostate cancer care.

There's a wide variety of different next-generation PET imaging agents out there, and this is a nice slide from a recent review paper, just to kind of give you a sense of all the different things out there. This is really meant to be an educational video for patients, so I'm really going to focus on this one that you see over here on the left-hand side of the screen called PSMA or prostate-specific membrane antigen. So as I mentioned, PSMA is short for prostate-specific membrane antigen, and this is a test that's highly sensitive for detecting prostate cancer. This method is not yet approved by the FDA as of the time that we're recording this video. Hopefully within the next year or so, probably in 2021, we'll see the FDA approval of some of these agents, hopefully making them more widely available.

PSMA is a protein that's expressed on the surface of prostate cancer, which you can see here on the left side of the screen. And the reason why this method works well is that this protein is very specific to the prostate tissue, but has low expression on other backgrounds. So it lets us see very specific sites of prostate cancer recurrence. This test is mostly used in two settings. The first is in patients with a new diagnosis of high-risk prostate cancer, and the second setting is biochemical recurrence after definitive therapy. Biochemical recurrence is what happens to patients after they've had a definitive treatment like surgery or radiation, and then their PSA or prostate-specific antigen, not to be confused with PSMA when their PSA levels start to go up. That means that the cancer is probably back, but we don't yet know where the cancer is, so we don't yet know what the best treatment is. It is the job of the PSMA PET scan to detect these sites of disease recurrence.

Why is PSMA PET valuable when you compare it against other diagnostic methods? Well, the main reason is that it has increased sensitivity for detecting metastases or spread outside the prostate. If the cancer has spread outside the prostate into lymph nodes or bones or other tissues that has major implications for the treatment of prostate cancer and will change the treatments that a patient may undergo. And this PSMA PET can often detect lesions that are not seen using structural imaging like CT or MRI. It can help in planning treatment and particularly it can guide surgery or radiation to help target small metastatic deposits and hopefully slow the progression of the cancer.

PSMA PET is a safe technique, thousands of patients have been scanned worldwide, and it does involve the use of radiation, but the radiation dose is similar to that from other methods, for example, CT scan and bone scan. However, I wanted to again emphasize that this method is investigational and not yet widely available.

Let's take a look at what some of these normal images look like. So here's a typical picture that we look like when a patient gets a PET scan. And it doesn't look like a normal person, right? And that the reason is it's because only some of those tissues are lighting up. So what we see in the region of the head is a lot of lighting up of the lacrimal and salivary glands, the tissues that make saliva, and then there's really nothing much going on in the chest, very little normal uptake. And then in the abdomen, we see the liver, spleen, kidneys, bowel, and bladder, and that's all just normal, indicating the ways that this tracer is cleared through the body.

So let's take a look through what it looks like when patients do have spread outside the prostate. So the first image over here on the left, you can see that there are three additional spots over here in the region of the pelvis, these indicating the sites of metastatic deposits in the pelvis. Here's another patient, and now here, you can see sites of uptake in the region of the chest. So these are lesions in the bone and in the lymph nodes in the chest. Here's another patient who has multiple lymph nodes that have increased uptake, you can see here in the region of the pelvis and abdomen. And then finally here on the right side of the screen is an example of a patient who has diffuse spread to their bones, you can see throughout their skeleton, they have increased uptake of the tracer.

And this is an example of what we see when we see positive scans, meaning that we've isolated the sites of metastatic disease. And in some cases, finding these metastases might help the patient's physician choose a different treatment for the patient. Of course, it's good to think about these things in the abstract and look at the big picture, but let's talk about how this might affect an individual patient. I'm going to present here a case study. So Mr. A is an 80-year-old man with a history of prostate cancer. He had a prostatectomy way back in 2000 and underwent salvage radiation to the prostate bed in 2013. That means that the cancer was thought to be coming back in 2013, and they empirically did a broad field of radiation to the prostate bed, thinking that it came back there. He again had a rising PSA up to 1.4 in 2019. He underwent a PSMA PET scan.

Let's take a look at his PSMA scan results. Here's the picture. So what we can see is that there's an additional site of uptake in a lymph node here in the chest. You can see it's this bright spot here right in the middle of the scan. We look at this as well using these special high-resolution fusion images. In this case, the images are fused with an MRI and you can see that lets us more precisely localize the site of the metastatic deposit. So in this case, what it showed us was that this was a lymph node in the region of the chest called the mediastinum. Once this site was understood, the patient elected to undergo a highly targeted radiation to that lymph node. When that happened, the patient's PSA decreased afterward. So hopefully that indicates to you how this next generation scan can help change a patient's treatment for the better.

So there are many things we know about this scan, and there's still a lot of things that we don't know because this technique is still very new, as I mentioned, it's not yet approved by the FDA. We do know that PSMA PET is a highly sensitive technique for detecting prostate cancer. We also know that increasing the detection of small metastases can enable targeted therapies such as surgery or radiation, which were not possible before this method. However, what we don't yet know is do these new therapies targeted by this method extend the patient's lifespan when you consider it in the broad clinical picture of all the patients out there. And this is an area that's under investigation, and we probably still won't know this for several years to come.

This agent is being tested in many clinical trials, including at UCF or the University of California in San Francisco Medical Center, where I work. If you are interested in participating in a PSMA clinical trial, please don't hesitate to contact me. My information will be at the end of the presentation. I will be happy to connect you with someone near you who is conducting a study in this area. Here's my email. It's . So I'd like to thank you very much for your attention. I'd like to acknowledge the other people who work with me together on the prostate cancer diagnosis and treatment series as part of the Prostate Cancer Outreach Working Group. Thank you very much for your attention today.