Dr. Ashwani Rajput and Dr. Mark Markowski, the Director of Genitourinary Oncology for the Johns Hopkins Kimmel Cancer Center in the National Capital Region, discuss the benefits of a multidisciplinary approach to prostate cancer and the treatment of genitourinary cancers in men. Hello, my name is Dr Ahani Raj, but I'm the director of the Johns Hopkins Tim Cancer Center in the Greater Washington DC area. Thank you for listening to my podcast about all the great things happening at the Kimmel Cancer Center in and around Washington DC. 2023 represents the 50th anniversary of the cancer center at Johns Hopkins. You can learn more about the amazing breakthroughs that we've been a part of in advancing cancer care at Hopkins cancer dot org. You can also subscribe to our podcast wherever you're listening from today. We're gonna talk to Doctor Mark Makowski. Doctor Markowski is an associate professor of oncology in the Johns Hopkins University School of Medicine and he sees patients at both S Memorial Hospital in Washington DC and at the Johns Hopkins Hospital in Baltimore. He now also serves as the Director of GU Oncology in the DC region. Welcome, Doctor Murkowski. Thank you for having me. I'm looking forward to our conversation today. Super well, first of all, tell us what is GU oncology that encompasses a number of different cancers. I generally think of it as anything touching urine involves us. So kidney cancer bladder cancer, prostate cancer are the three biggest cancers that we treat. But we also see cancers of the testes as well. So those would be the big four as I would describe them for the cancers that we treat under a gu umbrella. And is there any specific cancer of the ones that you've described that you treat? I primarily treat patients with prostate cancer. And I also see patients with kidney cancer as well. Well, let's talk a little bit about prostate cancers. It's one of the most common cancers in men who's at most risk, prostate cancer is the most common cancer in men outside of some superficial skin cancers. I think in terms of who's at risk, I'm gonna start being a little bit more general here and just say, look, prostate cancer is a disease of the aging. So we think about men who are getting older and we focus primarily in men in their fifties and sixties. And that's kind of our sweet spot when we're thinking about prostate cancer screening and talking about prostate cancer. So I think as a starting point, I will just say those at risk are those men who are getting older. So basically, that's everyone. Right. All right. Well, you know, as we talk about some of our screening policies, we can dig down a little bit in the specifics. Ok. Well, let's talk a little bit about that. So how do you determine who needs to be screened for prostate cancer. If it's a disease of aging and every man is at risk, it's something to is looked at for decades. The question really is who needs to be screened for prostate cancer? Meaning whose life will be threatened if they were to develop a clinically significant prostate cancer versus somebody who may have a very low grade prostate cancer who's in their eighties and will go on to live a full healthy life without ever needing to know they have prostate cancer. And that's been an ongoing focus of research. I will say, you know, as we think about who to screen, we think about risk factors for prostate cancer development. Some of those risk factors are modifiable and some are not. We already talked about it. Everybody's getting older, right? So we know that getting older puts you at risk of having prostate cancer. But I can't change that. There's also genetics, like in all cancers, there are certain genes that we've identified that if they are mutated within a family, put you at higher risk of getting prostate cancer. So for those who need to be screened, somebody with a family history of prostate cancer, especially if dad had prostate cancer, then we tend to screen those offspring, those sons of that patient. But also cancer in general, we know prostate cancer runs in cancer families. If grandma had breast cancer and mom had breast cancer, that would certainly raise some suspicions for that patient to go ahead and get screened for prostate cancer. So genetics, although not modifiable would be something that we would look at family history and then there's some modifiable risk factors that may play into prostate cancer development such as diet exposures. And that also relates to geographic area. And then we can work our way into race and ethnicity. I mean, we know that Asian men on the whole have a lower risk of prostate cancer than Caucasian men and African American men. And we know that Asian men who live in Asia have a lower risk of prostate cancer than those same Asian men who then moved to the United States. Their risk of prostate cancer starts to approach more of Caucasian men in the United States, right? So there is some exposure slash dietary history that may play into the need to screen somebody for prostate cancer and that is modifiable and that's what most patients want to talk about, ways that they can modify their prostate cancer risk, which we could talk about in a minute. And then there's also race and ethnicity. So we know African American men have a higher rate of prostate cancer than Caucasian and Asian men. If you have, have an African American heritage and are an older male, like those are patients we want to screen. And so I guess that's kind of a poor man's overview of certain risk factors for prostate cancer. And that plays into who we need to screen when you look at screening guidelines. And there is a number of screening guidelines out there that I encourage your audience to look at. And most of the guidelines will revolve around age because that's a big factor. Normally we would recommend at least a discussion on screening for men age 55 to 69. Those are the men that we think if we can intervene upon early with an early diagnosis of prostate cancer, that we are gonna save lives. Moving forward as we get older into our seventies, those recommendations for screening go down because we think that if you get prostate cancer in your seventies, eighties and even nineties, that screening is not gonna allow you to live longer if you were to develop more advanced prostate cancers with all our breakthroughs and the you're more likely to die with prostate cancer than from it. So when we think about who needs to be screened, we're thinking about men in the age group of 55 to 69 and then we play in some of those risk factors that we talked about. So African American men in that age group, you certainly want to screen them in that age group. But maybe even earlier, if you have a family history of cancer, family history or prostate cancer, we certainly want to screen you in that window. Those would be the big ones here. It would be the genetics. So family history or you are known to have a certain inheritable genetic mutation like a BRC, A one or BRC A two mutation. We want to screen you. If you're an African American man, we want to screen you. And if you're in the age group of 55 to 69 we wanna screen you what is involved in screening for prostate cancer. The two most common ways we screen for prostate cancer and this is typically done with our primary care doctors would be to check a PS A level, a prostate specific antigen level, that's a protein that gets excreted by the prostate into the blood and can be readily measured. And now some level of PS A in the blood is normal somewhat arbitrarily. But we've defined a abnormal level of PS A of 4.0 as we're thinking about the numbers 4.0 is that cut off that we start to think about looking for prostate cancer. So there's a PS A check that happens and there's also an examination, your doctor and your urologist can examine your prostate direct. There's something called a rectal exam where the doctor can feel the prostate through the rectum and they're looking at size. So how big is your prostate and the texture of the prostate? Is it lumpy bumpy? Are there nodules there that would maybe indicate prostate cancer or is it smooth and a normal consistency? And it's just a normal benign part of aging that your prostate cancer is a little enlarged. And so we kind of use both together to help our decision tree about pursuing biopsy and further work up in terms of how do we do the screening? It's gonna be a PS A check with an examination and we'll go from there. So the PS A check you mentioned is a blood test, right? So a blood test and the digital rectal exam during that physical And does that digital rectal exam then start at age 55 as well? Or do you recommend that that happen earlier? If you look at the guidelines, 55 is the typical age group that we would start with. However, for those patients experiencing changes in their urination pattern, maybe you're getting up more frequently a night to go or maybe you go a lot throughout the day. Maybe it's hard for you to stop going or start going or your stream is weaker. Any changes that happen along the way I think is gonna change how we investigate because it's not only prostate cancer that we're looking for, we're looking for benign enlargement of the prostate that with certain medicines, we can shrink the size of the prostate or open it up so that the urine flows a little bit more freely and it relieves those symptoms. So I would say 55 if we're thinking about a generic age cut-off for people to get screened. But if you're having symptoms, then I would suggest that you get examined earlier. For sure. Let's say if a gentleman comes in and gets screened and does have an abnormal finding on the physical exam and potentially an increase to PS A on the blood test. What are the next steps most commonly? You're going to be referred to a urologist. So, a urologist is a surgeon who specializes in the same region that I specialize in kidneys, bladder prostate and those doctors are gonna be enlisted. And I suspect that person will undergo a biopsy where a needle is placed into the prostate gland and they sample different areas of the gland looking for cancer. Is that an outpatient procedure or do you have to come into the hospital for that? No, it's absolutely an outpatient procedure and the technology on that is getting better and better any time we put needles into patients, we worry about infection and bleeding and those kind of things with better technology, better imaging, we can identify certain lesions in the prostate that we may want to hone in on before we even do the biopsy. So it is an outpatient procedure. You show up to the office, you get your procedure done, you get to go home and then hopefully in about a week, we get those results and we can start moving forward. So let's talk a little bit about that. And earlier in our conversation, you alluded to something called a clinically significant prostate cancer. What does that mean comes in, he gets his biopsy and you know, your world kind of stops when you hear the words, you have prostate cancer. So then what? That's a great question. Going back decades, we ascribe a certain scoring system to prostate cancer. You don't get a, just a generic, you have prostate cancer and it's a one size fits all approach. We characterize the prostate cancer and how it looks like under the microscope. And there's something called the Gleason score that's been developed many, many decades ago. We still use it today where it gives us an understanding of how that cancer is, one of how it looks like. But also it allows us to predict how it would behave moving forward. So right now, we score patients with a Gleason score of 6 to 10. But Gleason six prostate cancer is the wimpiest prostate cancer that we come across. And many times those patients with Gleason six can be safely observed. We put them on something called active surveillance where they're followed with PS A. They occasionally get a repeat biopsy and we make sure that Gleason six prostate cancer is there and the prostate is not getting outside the prostate and it saves our patients from surgery and radiation and treatments they may need because they're gonna outlive that prostate cancer. And then as we get to Gleeson 789 and 10 being the most aggressive. That's when we start to think about treating that prostate cancer because we think if we treat it earlier rather than later, we're gonna save lives doing that. So, some of the options that you've just talked about was depending on the grade of the cancer that our pathology colleagues tell us would make some determination of either just observation and watching versus the treatment. If it's a higher grade. Can you talk a little bit about the treatment? And what is the multidisciplinary approach at Johns Hopkins local prostate cancer? What do I mean by that? So, prostate cancer that is confined to the prostate gland and that's gonna be most of the patients that we see. So if you get screened, your PS A is elevated, you get a biopsy, you have Gleason eight prostate cancer. Sometimes patients will undergo a cat scan or a bone scan to see if the cancer has spread to different organs if it has not. And again, as we're screening patients, we're getting better at screening more patients are presenting with earlier prostate cancer that we talk about treating them with a curative intent. We want to get rid of this prostate cancer for this patient. And there's really two ways that we go about doing it. One of which is surgery, something called a prostatectomy where the prostate is removed and that's done by our urology colleagues. So the same doctor that performed the biopsy would typically do the prostate surgery. Patients can elect for surgery, the other option leaving the prostate in place. These patients don't undergo surgery, they undergo what's called radiation therapy. They would see a doctor called their radiation oncologist. And those doctors specialize in using radiation, conventional radiation proton therapy photon therapy. What they're doing is they're shooting at that prostate cancer in place and they're killing it. They're using radiation therapy to get rid of that prostate cancer and leave that glands in place. In many cases, patients can choose either they may choose based on side effects or personal preference. Maybe they're not a good surgical candidate because they have high blood pressure or have heart attack and we don't want them to undergo anesthesia and surgery. We would maybe push them to radiation. There's a number of different factors that would push us one way or the other. And I think you alluded to this. That's why I think the multidisciplinary approach is so important. If you're a patient who comes to us at s hospital with a new diagnosis of prostate cancer, many times, we're gonna see that patient in what we call the multidisciplinary clinic. What happens is that that patient will come for the day, hopefully with their family and we're gonna have our pathology. Your group, look at their biopsy specimens and give them another Gleason score and have another look at that prostate cancer itself. We're gonna have our radiology team come and look at any MRI that was done or cat scan or bone scan that was done to make sure that that cancer is appropriately staged. You're gonna see our urologist, our radiation oncologist and even somebody like myself, a medical oncologist, all of whom specialize in prostate cancer. This is a very focused group of individuals who have and expertise in prostate cancer. So, the urologist does prostate surgery. The radiation oncologist is just radiating prostates and I'm seeing mostly prostate cancer. We can give you a very prostate cancer centric approach to your prostate cancer. Maybe you walk into that meeting, thinking that you wanted surgery and maybe you walk out with a radiation plan or vice versa. So we try to customize that plan to the patient based on what they want and what we think their best outcome will be super. So that multidisciplinary team then really has a lot of communication and really caters to that patient's disease so that the outcome is the best, as you said, but is there a difference in outcomes between surgery and radiation? So in general, no, there's been some studies to look at this patients with prostate cancer do well, regardless of which pathway they choose? Ok, that's kind of a more general approach. What I encourage patients to do if the outcome is gonna be the same, whether you choose radiation or surgery to some degree, it's on us to explain the risks and benefits of both. And then it's up to the patient to decide kind of what's best for them as well. Some patients don't want to undergo surgery, they're uncomfortable with that process. But then maybe radiation is the best approach. There's other patients that just want that cancer out. They just say look, get anatomy and I want to do surgery. They may choose based on that. They may choose upon side effects toxicity. Whereas the risk of surgery are somewhat upfront. You have anesthesia, bleeding risk, infection and you can have complications coming out of surgery, er, child dysfunction or urinary incontinence and that's been upfront risk. Whereas the risks of radiation may be more delayed, you may get some irritation in the bladder or irritation in the rectum that may affect your bowel movements or how your urine looks in the years to come. So there's different ways that patients may choose how they want to move forward. So it's a preference on how they feel, but also about the side effect profile as well. Primarily. And most importantly, of course, as you alluded to, you're talking about curing the patient of their prostate cancer. But the side effects, uh, that you alluded to that are functional, whether it's urinary incontinence or erectile dysfunction. How do you manage those many times they're managed with medicines, particularly erectile dysfunction. That's a big issue for our men and a concern for their men. So there are pill medicines that work like Cialis and Viagra and those are good enough and sometimes they need more therapy. Sometimes there's injections that may be needed to help or other assist devices to help them achieve and maintain an erection that may become an issue for them. For the urinary incontinence, we typically encourage what we call pelvic physical therapy. And we have dedicated physical therapists that helps strengthen the pelvic muscle there to make sure that your body is strong enough to hold that urine. So there is no leakage. If there is some leakage that is bothersome, there are devices that can be put in an artificial sphincter that serves as the sphincter of the bladder that a patient may have put in place that is generally very comfortable that allows them to urinate relatively normally. So there are ways to manage those side effects in the long term. So if they do not affect your quality of life, you had mentioned to us that uh once the man is diagnosed, you'll often review imaging to make sure that the prostate cancer is what you called organ confined. If a man comes to you and the prostate cancer is not just confined to the prostate, where can it go? And then at that point, what are options for treatment? So like all cancers, prostate cancer, if not caught early, can spread to other areas of the body. And in that case, we consider it to be a metastatic or stage for prostate cancer. Generally, prostate cancer likes to go to the lymph nodes. Those are typically the pelvic lymph nodes and some of the lymph nodes that go up into the back area just because they are adjacent to the prostate gland. So, lymph nodes are a big area. Bones is another common area for prostate cancer that it likes to go lymph node and bones would be the two most common areas. It can go to the liver, it can go to the lungs, but those are less common particularly in a new diagnosed patient. So I would say lymph node and bones would be the most common place. And then what are options for treatment for a patient with stage four cancer, the backbone of therapy for a patient with metastatic prostate cancer would be something we call hormone therapy or androgen deprivation therapy. So we know that testosterone. So, testosterone is the predominant male hormone that drives the growth and spread of prostate cancer. And we've found over the last 80 years that if we can block the effect of testosterone or lower the testosterone in the body that will significantly reduce the ability of the cancer to grow. And essentially what happens is that the cancer will start to die off. The PS A numbers will go down, tumors will shrink down. Now, I will say in general, we do not cure patients with metastatic prostate cancer, but the survival of those patients with the right therapy, particularly hormone based therapies is in the range of 7 to 15 years. Some patients live even longer than that. So, if you have a patient who has metastatic prostate cancer, you know, in their seventies and eighties, our strategy is gonna be to manage it like a long term medical problem. And we're gonna use our hormone therapies or if there's chemotherapy that are needed, we're gonna use all the tools available to hopefully ensure that that patient goes on to die of something else and not their prostate cancer. Wonderful. So really, no matter what stage of disease a man may present with prostate cancer, there are a lot of options that can be very successful in managing it. That's uh really encouraging. Mark. Are you involved with any clinical trials or are there clinical trials available for patients with prostate cancer? At S there are a number of clinical trials available for patients with particularly advanced prostate cancer or metastatic prostate cancer. Those trials are constantly evolving and they're changing. So what we have today in six months may be different and 12 months may be different and I'm sure this is true across the board for cancers, but especially in prostate cancer, if you look at the treatment options now available for patients in 2023 versus 20 years ago or 10 years ago or five years ago, we keep building and building and building more and more treatments into the treatment regimen and that's because of clinical trials. I would say we're part of the research process here at SBLI and Johns Hopkins in general, we're trying to push the cutting edge here of technologies and different treatments for patients with prostate cancer. There's a real benefit to patients who go on our trials. And I think this is important to get out there that a lot of patients when we talk about clinical trials, they're worried that they're gonna get the placebo, that they're not gonna get a real treatment that they're just gonna be a guinea pig. What's good about the trials in the oncology world? Is that the quote unquote worst case scenario is that you get the standard of care. So when we talk about control arms or placebo arms or trials in oncology, you're gonna get what we consider to be the best standard of care. So if that's chemotherapy drug X, then that's what you're gonna get at bare minimum. But you also have a chance of getting a newer technology, a, a new drug that's not yet FDA approved or available and see if it works for you. Sure, there's a possibility of having a side effect from the treatment, but it allows you to get access to maybe a technology that works for you before anybody else can before it gets FDA approved in a number of years from now. So there's a lot of benefits there. We're certainly involved and we have a number of different technologies for patients. Mark you alluded to, um being on the cutting edge, having access to these uh novel therapies. Is there anything particular that you're excited about? That's on the horizon in the world of prostate cancer treatment? Absolutely. One of those treatments that we always talk about being on the horizon is actually here and that's something called radio liga therapy. And patients may know it as Luisi or Luti ps ma or Pluto. What happens is that the patients get a medicine through the IV part of that medicine seeks out and binds the prostate cancer. Almost all prostate cancers make something called PS ma prostate specific membrane anti a protein that sits on the top of prostate cancers. And about 80 to 90% of prostate cancers make it in abundance. So there's a lot of it and part of the medicine will bind to that PSMM, this is a pretty prostate specific targeted agent binds to prostate cancer and the other part of the molecule has some radioactivity attached to it. So when it binds to that prostate cancer, that radioactivity can then kill the prostate cancer where it lives, it is able to bind to low levels or small amounts of cancer in the body, also large amounts of cancer in the body. And it's been a very effective treatment tool for patients with metastatic prostate cancer. So we always talk about that being on the horizon, but it's been FDA approved about a year ago and it's going into patient. And so to build on that, we have the 2nd and 3rd generation of these compounds that are starting to be brought into the clinic into clinical trials. So how can we make that Luit ps ma better, more effective, safer for patients with better outcomes? That's one of the areas that as a field we're very excited about. We're also using high doses of testosterone, something called bipolar androgen therapy. And this is something that we developed here at Hopkins and at SBLI, whereas these patients have been on hormone suppressing medicines for a number of years. Well, we found that giving them back high levels of testosterone and different formulations can be an effective form of prostate cancer treatment. And we're also working on different immunotherapies way to make your immune system fight off prostate cancer. And that's been a real challenge in prostate cancer. But we're developing newer technologies and models to kind of use the immune system to go after prostate cancer. And I think those are some big buckets that we're looking at the radio ligands, testosterone therapies, immunotherapies. And that's in combination with our standard hormones and chemotherapies and targeted agents that we already use in prostate cancer. So I think we're making great progress. Well, truly, it is an exciting time in oncology with all these advances and therapeutic options. Is there a specific area of interest that you have in the research arena? So I've been very focused on trying to develop treatments for prostate cancer outside of the standard hormone based therapies, right? So when you go on a hormone suppressing medicine or testosterone suppressing medicine, that certainly can have quality of life effects, hot flashes, fatigue, decreased libido, bone weakness, and those things over the long term that can really affect the quality of life. And so what we're trying to do is I identify are there targeted agents that we can use outside of hormone therapy that are effective against prostate cancer but may not come with those quality of life issues. We already have some today with medicines called Park inhibitors where if you have the right mutational profile in your cancer, you can take a targeted pill medicine that doesn't target the hormone access, that targets that mutation directly and still lead to good outcomes. So I think in more general terms, we're looking at what we call non castrating thera these as an effective way to treat prostate cancer and preserve those quality of life issues for patients. Wonderful. Well, thank you for joining us today, Dr Markowski. It's been really informative and really appreciate all of the work you're doing in uh men's health. Thank you to all our listeners also for joining us today. And again, you can subscribe to all of our podcasts by searching for the Johns Hopkins Kimmel Cancer Center wherever you are listening or visiting Hopkins cancer dot org forward slash podcasts. Thank you.