Professor, Nuclear Radiologist & Researcher at the Winship Cancer Institute of Emory University, David M. Schuster, MD talks about a new way to detect prostate cancer in patients.
Interview conducted by Ivanhoe Broadcast News in 2023.
We’re talking about prostate cancer. Some say if a man lives long enough, they will get it. Why is this so prominent? Talk to me about that.
Schuster: I believe 80 percent of 80-year-olds have prostate cancer of some form. The big question is, which are the types that can be ignored, and which are the types that need action? What we do in our field is try to determine which types need action and to help guide the action by finding the areas of cancer. This happens because of evolution. As we get older, cancer rates increase throughout the body and that’s just nature right now.
Once you get it, is re-occurrence common?
Schuster: Yes, it is. Depending on how one is treated. Assuming one must be treated and there are guidelines, but assuming one is treated, the recurrence rate is approximately 40 to 50 percent depending on the type of treatment. This is a major problem and one of the reasons why it’s a major problem is when it first recurs, the disease is often confined and can be retreated more easily. If the disease is allowed to progress, it can progress to a very lethal form called metastatic castrate-resistant prostate cancer. That is what we want to prevent or at least delay.
How is it currently detected?
Schuster: Traditionally, we use what we would call conventional or anatomic imaging, so CAT scan and bone scan were the traditional ways of looking at it. But as we developed greater tools, we found that a lot of diseases were being missed. MR or Magnetic Resonance Imaging is a great tool that is more appropriate for discovering prostate cancer initially and also for looking at the local extent if there is a recurrence. But MR is not always available, and it can also be somewhat nonspecific. In other words, a lymph node can look suspicious on MR, but it might not have cancer in it, and vice versa. A node may be very tiny, and it can have cancer in it, but it does not meet the criteria, so better tools are needed. We have a tool called positron emission tomography, where a small amount of a radiotracer is injected into the body and it goes to specific areas, in this case, cancer. We can look at where it goes using very powerful tools called PET scans. We have different radiotracers available. Early on there was a radiotracer called, carbon 11 choline, which was FDA-approved in the US. Also, fluorine 18 flucyclevine or agumin, was developed at Emory. These were tools that advanced our ability to see prostate cancer. Now we have a tool called prostate-specific membrane antigen, PET. PSMA, or prostate-specific membrane antigen, exists throughout the body, but more of it occurs in prostate cancer. We can use a radio tracer directed against this PSMA existing on the cell to find the prostate cancer.
How does a newly approved FDA fit into diagnosis and treatment?
Schuster: As physicians, it’s great to have as many tools as possible. You may say having more arrows in our quiver will help us defeat the enemy of cancer. So POSLUMA is one of the latest arrows and there are other PSMA radiotracers. There are three that are FDA-approved. This would be the fourth, but this is a unique type.
What is it and how does it work?
Schuster: POSLUMA is a radiotracer, also called RHPSMA 7.3. It was invented at the Technical University of Munich by a radio chemist there, Hans Jurgen Wester. We are now studying it in the United States, so this led to the FDA approval. This is a unique molecule. First, it is directed against the PSMA that exists in prostate cancer cells. It is a radio hybrid, meaning that you could swap in different kinds of radioactive atoms depending on what effect you want to get. The one that has been FDA approved initially has what we call foreign-18. It’s a positron emitter, and that’s what we’ll use for PET scanning. This allows us to find the tumor, but you could also swap in a different type of radioactive substance that gives off killing radiation like lutetium-177, which gives off beta emissions, which are electrons, which can kill cancer. That is still under study. That’s not FDA-approved yet, but the idea is that you just be able to swap in what you need for the job at hand. In other words, this is something called the theragnostic, where we use the same radio tracer backbone to find the disease. Then we use the same radio tracer backbone, but a different kind of radioactive substance, and more appropriately, it would be called a radiopharmaceutical to then deliver the killing blow. You may say this is like a missile directed against PSMA, but then you could swap in the payload depending on what you need to have done.
Can you talk about the Phase Three spotlight study?
Schuster: Spotlight, there were two registry trials, lighthouse, and spotlight. Lighthouse was for patients with higher-risk primary prostate cancer who are going to have surgery including prostatectomy and pelvic lymph node dissection. Spotlight you may say the sister trial which examined patients who had biochemical recurrent disease. There are different definitions of what we consider biochemical recurrent. It’s based on PSA levels, and prostate-specific antigen, and not to get into too much detail, but it depends on how one is treated initially. There are different criteria. However, all these patients had biochemically recurrent disease. Somewhere we know that because the PSA levels, which are a very powerful tool in the blood, were elevated. Now it just becomes a matter of where is the disease. This study enlisted over 350 patients. This was a multi-center multinational effort. We looked at these patients getting the Posluma scan at the time was RHPSMA 7.3 before FDA approval. Then this was compared to the best comprehensive reference standard, something called the composite reference standard. Ideally, you’d like to have a biopsy, but you can’t biopsy everything in the body that’s abnormal. Not only that, but it may not be appropriate to biopsy in certain areas. We used other imaging standards where you could say, we’re convinced that is cancer by the preponderance of the evidence. We found very good results, that the detection rate was very high across PSA levels and as with any imaging with prostate cancer. The lower the PSA, the lower the detection rate. But even at the lowest PSAs of less than 0.5, the detection rate was in the 60 percent and that’s very good for PSA that low. Then as the PSA got more elevated, the detection rates went into the nine ’90s.
What would the results be? Is this a game-changer in this field?
Schuster: In general, I think that each advance we do has the potential to be a game changer. PSMA imaging is also a game changer. However, I would say it’s a step advance from what we had before in terms of pet scanning. But it’s an even greater game changer compared to conventional imaging. Now as far as this molecule, it could be a game changer because it has very high affinity. I just want to stress that no head-to-head comparisons have been done with the other PSMA radiotracers. But there’s also the potential for lower urinary activity. This is important because when we have a very high activity of the radiotracer in the urine, the body has to get rid of it. Then it can obscure cancer recurrence in places where it recurs the most, such as the prostate bed. The prostate bed is right next to the bladder. It’s like trying to find a pin light next to a very bright light bulb. If you turn down that light bulb, you’ll be able to see that pin light better. More research needs to be done with that, but that could potentially help us as well. There are advantages to most prostate cancer express PSMA, that’s one advantage. About five to 10 percent don’t and this is where the other radiotracers might come in handy, that were developed before, such as flacclavine or agumin pet. Again, it’s yet another arrow in the quiver to overuse the metaphor.
When would you use this and when would you not?
Schuster: I would use it when potentially have actionable findings. For example, let’s say a patient has very low-risk prostate cancer and per the National Comprehensive Cancer Network guidelines, this is something that you would just do surveillance with and has a very low chance of having metastatic disease. You wouldn’t want to use it for that. Or let’s say a patient has a lot of other illnesses. You may say that patients are not necessarily appropriate for us to find the disease and do something about it. You want a case such as the FDA label primary prostate cancer, where there is a suspicion of metastatic disease. Those are generally the higher risk levels. Also, biochemical recurrence, where you’re going to get some actionable finding that you feel that you can do something about in that particular patient, in the individual patient. That’s what’s very important. That decision must be made between the doctor and the patient and personalize the use of the study. You just don’t want to throw it blindly at just any situation.
Anything that we might have missed that you want to add?
Schuster: I think that I was the coordinating investigator for Spotlight, and we are very proud that Emory was at the center of this investigation. Other studies continue with this radiotracer as well as the radio hybrid variance. We are excited to be part of those studies in the future as well.
END OF INTERVIEW
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