Prostate cancer is the most common type of cancer among America’s veterans population. An estimated 500,000 veterans are living with a prostate cancer diagnosis today. So it makes sense that the Veterans Health Administration would make prostate cancer research a priority. One of the latest developments is a partnership with the Prostate Cancer Foundation. Among other things, it’s helped to fund research into precision oncology – treatments that are tailored to each patient’s specific physiology. Dr. Matt Rettig is the chief oncologist at the VA of Greater Los Angeles. He joined Federal Drive with Tom Temin to talk about some of the research questions VA’s trying to answer.
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Dr. Matt Rettig: Prostate cancer is the most commonly diagnosed major malignancy amongst veterans. In fact, it’s the most common major malignancy amongst males in the general US population, with somewhere around 200,000-250,000 new cases per year. Currently, there are approximately 500,000 veterans who are alive with a diagnosis of prostate cancer, and about 16,000 to 17,000 of them who have the most advanced stage of the disease, that is called metastatic prostate cancer, meaning it’s spread beyond the prostate to another organ. So it’s a big problem. It’s associated with a lot of complications, what we call morbidity, as well as unfortunately, mortality. And so it’s a high priority malignancy for the VA so that we can better understand it and better treat it for our veterans.
Jared Serbu: As far as we know nothing specific about the veterans population per se, other than it tends to be older. So it is the rate of prostate cancer in the veterans population general reflective of what you’d see in the same age groups in the general population?
Dr. Matt Rettig: It is similar, there are some important questions that need to be addressed. One is the role of Agent Orange. So Vietnam veterans who’ve had boots in the ground on in Vietnam War are considered to be exposed to Agent Orange, which is a service connected disease, prostate cancer associated with Agent Orange. In addition, the VA population is over represented by certain minorities, most notably African Americans as compared to the general population. And African Americans have a higher incidence of prostate cancer. And that’s true in the VA system, as well as a higher mortality rate in the general population. It’s not clear that there’s a major difference in mortality in the veteran population. One of the major factors that results in health disparity between African Americans and Caucasians is access to care. And that is a factor that is minimized within the VA system. And in fact, many treatments that are used for prostate cancer patients, especially advanced prostate cancer patients are more effective in African Americans than Caucasians.
Jared Serbu: Interesting. So you mentioned Agent Orange is one question, what are some of the other big research questions around prostate cancer that VA is working on specifically right now?
Dr. Matt Rettig: Yeah, so prostate cancer is a major area of focus of research. And when we think about research, we think of laboratory or bench research, and clinical research, and something in between, which is called translational research, which bridges the divide between the lab and the clinic. And all three of those types of research are ongoing at the VA. Some of the big questions that we need to answer is what is the role of certain environmental exposures? Agent Orange is a good example. In the biology, the aggressiveness of prostate cancer, does it result in a different version of prostate cancer that’s more aggressive, that has different genetic findings associated with it? And that’s an important question that’s ongoing, and then hopefully will be answered in the near future. Along those lines, we also want to know if patients who have Agent Orange is associated prostate cancer have a different response to therapy? also an important question that’s ongoing, and something that’s being addressed in a number of clinical trials, including some that I am conducting. Another big question is whether or not we can use the patient’s genetic background, the specifics of the patient’s tumor, the genetics that are unique to the patient’s tumor, in order to select the right treatment for the right patient. So historically, using drugs for cancers, including prostate cancer, has been kind of the throw the spaghetti at the wall approach where one size fits all And clearly, that’s not the ideal approach. We want drugs that are going to have a higher likelihood of working in an individual patient. And knowing the specifics of the patient’s tumor is really critical in order to make that happen. And we do that by performing genetic sequencing on the tumor, and are able to pair a specific genetic mutation with a specific therapy. That’s not done in all patients. That is the sequencing is done. But it’s not all patients that have a mutation that can be paired with a specific drug. But the number of genetic changes that can be paired with a specific drug is increasing. And hopefully, we have we’ll have a drug for it for every specific mutation in the relatively near future.
Jared Serbu: And that that whole concept you’re just talking about, I think, falls in the bucket of what’s sometimes called precision oncology, right? You mentioned genetic sequencing is a big part of that. But are there other factors that you look at to help tailor that treatment to a particular individual beyond the genetic sequencing?
Dr. Matt Rettig: Yeah, so that’s, that’s exactly right. So precision oncology is basically using patient specific features and characteristics that allow the selection of a specific therapy, a drug that is most likely to work. Now, the genetics is really the driver of precision oncology. But there are non-genetic, what we call biomarkers, factors, that can be used to select patients for therapy, including fairly straightforward clinical factors. So, for example, we know that African Americans respond to a specific type of vaccine much better than Caucasians. And the difference is quite striking. So just by having an African ancestry, one is more likely to respond to this particular treatment. So we use clinical factors that are also what’s called imaging biomarkers where we have state of the art PET scans that can tell us what the patient’s prostate cancer is like, does it express a specific protein that can be targeted for therapy, and those are coming online. The scans have been now FDA approved. And there’s therapies that are going to be imminently approved, based upon certain imaging biomarkers and imaging characteristics. So the list goes on and on. But genetics is the main driver, but other factors are used to select the right drug for the right patient.
Jared Serbu: And how mature is this whole concept of precision oncology in the prostate cancer space? Do we have any way to quantify how much more clinically effective it is than the throw the spaghetti against the wall approach that you mentioned?
Dr. Matt Rettig: Yeah, so it’s still in its relatively early days. So the technology to identify the genetic mutations is fairly mature. And the VA will do that on any patient with advanced cancer. In fact, not just prostate cancer, any cancer. The proportion of patients who have a mutation that would qualify them for a precision treatment varies from cancer to cancer. So about a third of all prostate cancer patients with advanced disease. The question is, really, can we get the sequencing done on a national level, so that there’s no veteran that’s left behind the VA is a huge integrated healthcare system. Of course, it’s the largest integrated health care system in the United States, there are over 150 different VA medical centers, and that doesn’t include all of the outpatient clinics. And as a consequence, there is variability in the knowledge base and the resources that an individual VA may have. So what we want to do as part of the precision oncology program is to provide care to veterans, irrespective of their geography, we have another number of programs that have been initiated to achieve that. So veteran doesn’t have to be at one of the main academic VA medical centers in order to achieve precision care. And so that’s a really important feature of of the precision oncology program in prostate cancer, so that we can democratize precision oncology amongst all of our veterans. This project of precision oncology in prostate cancer has been going on since 2018. It was a key strategic partnership that the VA has started between the VA and the Prostate Cancer Foundation, which is the largest philanthropic institution in the United States in the world, for that matter for prostate cancer research and the prostate cancer. foundation initially funded this with $50 million. So it’s an incredible gift that the VA has received. And the VA has now expanded on this so that the program can reach more and more veterans.
Jared Serbu: And I assume one of the functions of that partnership would be to help export any anything that you’ve learned in the VA setting to the broader health communities. That a fair assessment?
Dr. Matt Rettig: Yes, absolutely. So the VA hasn’t has incredible resources in terms of data mining, a huge population of veterans. And when we put databases together, we don’t want to keep it just for ourselves. We want to make it accessible to researchers in the academic community who might not be at a VA so that we can learn the most from the the data and the patients that we do have.
Jared Serbu: Last thing I wanted to get to before we run out of time here is a specific clinical trial that I know you designed and worked on, where I think you’re taking some of the drug therapies, or at least one drug therapy that’s common for prostate cancer and trying to see if it’s effective in COVID-19 patients. I’m gonna let you pronounce the drug for us, but tell us what what questions you’ve been trying to answer through that trial.
Dr. Matt Rettig: Yeah, so this was a study that we initiated last year, towards the height of COVID. Of course, we’re having a resurgence, at this time, at least in in many states. And we were looking for a novel way of treating COVID with an existing FDA approved drug, drug obviously wasn’t approved for COVID, but can be repurposed for the treatment of severe COVID. So we tested a prostate cancer drug that’s commonly used as a hormone therapy called Degarelix. And what it does is it temporarily suppresses male hormone levels. And the rationale for this testing this type of therapy amongst COVID patients was related to the mechanism, the manner in which the virus enters human cells, the target cells, for example, on the lining of the lungs. Well, there was a study published in March of last year, a landmark study, which demonstrated that the virus uses two key proteins on the surface of cells to gain entry, it’s like the the door that it needs to open in order to get into cells. And these two proteins, the names don’t matter, but one is called ACE2, and the other one’s called TMPRSS2, are well known if you’re in the field of prostate cancer, because we know that they’re tightly regulated by male hormones. So male hormones cause more of these proteins, this door that the virus uses to get into cells to be expressed or present on the surface of the cells that are targeted by COVID. So the idea is that if we can temporarily suppress male hormones, and we would lower the amount of these proteins, this doorway to entry of the virus into the into the target cell, and thereby effectively treat severe COVID. So we can conducted this study., and it turns out, we were able to do it very, very rapidly, because we were using the clinical trials infrastructure of the precision oncology program, which was already in place, but was kind of on semi hold during COVID. So the infrastructure was already there. The VA rapidly funded the study, the study was completed and of course we were waiting for the results. It was a double blind study. And as the lead investigator, I’m not allowed to know what the results are until they’re completed. So this is something that we’re waiting for. There has been a study that was conducted with a similar drug in Brazil, which was published, which showed very, very striking reduction in the duration of hospitalization, and importantly, mortality of hospitalized patients with COVID. That’s in Brazil, it’s a different population. They have different resources in that country as compared to the United States. But it was an interesting merging of prostate cancer and COVID-19 knowledge into a clinical trial.
Jared Serbu: That is super interesting. I’m just curious on one last thing, by reducing those number of doorways on a cell surface, is the thinking that you can reduce the spread of virus throughout the body or really primarily in critical tissues like lung tissue.
Dr. Matt Rettig: Yeah, it really depends on whether or not the receptors that these doorways are regulated by male hormones on all tissues. We do see that they are regulated by male hormones in the main site of infection, which is the lining of the lungs in the respiratory system, the nasal cavity, the oropharynx As well as other important structures such as the heart. Some of the organs, we don’t know the regulation of. So some of it’s a little bit unknown, but the main source of the virus entering cells is the lung, and we do know that the lung uses male hormones to induce the expression of these doorways, these proteins that the virus uses.
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