Transcription:
The Basics of Prostate Cancer Treatment

Introduction: Here Weill Cornell medicines physicians and healthcare providers, check out the entire podcast library at weillcornell.org/podcasts.

Dr. John Leonard: Welcome to Weill Cornell Medicine, Cancer Cast, conversations about new developments in medicine, cancer care, and research. I'm your host, Dr. John Leonard. And today we will be talking about prostate cancer. Our guest today is Dr. Scott Tagawa. Dr. Tagawa is a Medical Oncologist and serves as the Director of the Genital Urinary or GU Oncology program at Weill Cornell Medicine and New York Presbyterian Hospital. And he's also the Medical Director of the Meyer Cancer Center Clinical Trials Office. Dr. Tagawa specializes in caring for patients with prostate bladder, kidney, and testicular cancers. He leads clinical trials in these areas and has particular expertise in the development of new drugs and ways to identify, target, and treat cancer cells. So Dr. Tagawa, Scott, it's great to have you here today. Thanks for joining us.

Dr. Tagawa: Thank you very much for the invitation.

Host: So tell us a little bit about kind of the basics of prostate cancer. How common is it? What are some of the risk factors? And I'll mention to the audience that several months ago, we had your colleague, Dr. Jim Who speak to us about prostate cancer screening, which is a huge and complicated area. So we're not going to spend as much time on that today, but for those of you who are interested in that area in the audience, you may want to look through our archive of podcasts, but just give us kind of the basics of prostate cancer from those sorts of parameters.

Dr. Tagawa: So clearly the major risk factor is male gender, prostate cancer is the most common cancer in men, excluding some of the skin cancers that happen with long-term exposure to sun. The numbers will go up and down and, you know, Jim Who was is the expert, when it comes to many things, including screening, so that the number of new diagnoses per year has gone up and down based upon how often the PSA blood test has been done in this country, but runs around 200,000 men per year are diagnosed in this country alone. And it runs about one in nine men in their lifetime will be diagnosed with prostate cancer. So it's the most common cancer. It varies in terms of the number of deaths per year. So the majority of men that are diagnosed actually will not die of prostate cancer, but mostly because it is so common, it generally is the second most common cause of death from cancer in men, following lung cancer.

So sometimes prostate and colon will by for number, number two or number three, but in the 2020 statistics prostate cancer is the second most common cause of death due to cancer in American men. And following male gender really it's age is the major risk factor, so much so that some would state that if a man lives long enough, and we look for it, it's going to be a hundred percent. I don't know if that's entirely true, but when someone dies at an older age of whatever, and we go looking at the prostate in autopsy theories, it's quite high percentage. But that also besides how common that is particularly with age, it also tells us that some of the cancers act in a fairly benign manner. I mean, they just sit there, don't really grow and don't necessarily bother the man. So that is one of the dilemmas of, as it comes to screening. But as you mentioned before, we'll leave that for the audience to go back and listen to that.

Besides age and gender, there are other risk factors. So certain socioeconomic risk factors exist in particularly African Americans have a higher risk, number one of being diagnosed with prostate cancer, and unfortunately also have a higher risk disease, meaning a more aggressive disease at diagnosis based on the numbers. And then one of the things that we're learning more and more about in prostate cancer, as well as a number of other cancers, is inherited genetic risk factors. So if you would have asked me 10 years ago, how many patients walk in the door with an inherited gene that puts them at increased risk? I'd say it's very small. Now, depending on a number of different factors, including how advanced their cancer is, meaning just in the prostate or spread as well as family history. It's anywhere from one in 20 to four in 20, would have an inherited cancer gene that would include prostate cancer as a risk factor.

Host: So it sounds like a big percentage of people, the scenario of diagnosis is screening tests, whether it's digital, rectal exam, PSA, some combination of that leading to biopsies, is that the majority of people? Is it subset of people, and kind of how common are the other scenarios, perhaps metastatic disease or some other symptoms or findings?

Dr. Tagawa: So it's still in this country, the most common way, someone who presents to me with prostate cancer would be what we'd call clinical localized [inaudible08:08] The most commonly, it's PSA being done. It is abnormal and I'd caution people there's no true normal level of PSA, depends a lot on the individual. And then they end up getting a biopsy. So that remains the most common. Although unfortunately, as PSA testing went down over the last five or more years, we do see a larger number of men walking in the door with cancer that has spread most commonly to lymph nodes and bone. So we do see both of those scenarios for the average man. It's exactly, as you said, there's a PSA. And the level of that does tell us something about risk in terms of how aggressive that will act. The prostate exam itself remains a part of screening because sometimes we will feel something as abnormal.

The most common location of cancer in the prostate happens to be where the prostate approaches the rectum. So we can feel it with the finger, that used to be the only way we could kind of get a sense of how big or how invasive that tumor is. But now we have additional imaging, most commonly with various forms of MRI, which is done to get the, you know, in today's world, one of the most detailed views of the prostate, but what remains out of the, between the PSA and the prostate exam and scan itself, the biopsy remains the most important. Number one, is there any detectable cancer on that sampling or not, but then once a diagnosis is made, how aggressive does it look? We look at something that's called the grade, has a man's name attached to it. Gleason score, basically, as we look under the microscope to tell how much unlike normal prostate does it look like? So the more unlike the normal gland it looks like the more aggressive, the higher, the number they get, the more aggressive it tends to act within patients. And then likely we've gone beyond just the finger, the MRI, we've gone a little bit beyond the Gleason score, and there's now a number of different genomic tests that will also help us give prognosis and help us with treatment decisions.

Host: So the typical scenario is you describe patients going to get a biopsy, they'll get an MRI, they'll get an exam before that obviously typically that biopsy and these other factors will lead to a risk assessment. And then it seems like in prostate cancer, like with many cancers, a multidisciplinary team is part of it, or at least consideration of multiple modalities. So maybe you can describe for us. I mean, clearly patients in some cases are going to have surgery. They may have radiation, they may also have medical management of one form or another. So can you describe a little bit about how that typically works, especially at our center where I know that's a big part of our care and then optimizing care for patients with prostate cancer, how does that work?

Dr. Tagawa: So globally, I would say that for most of our solid tumors, which are the most common cancers that are out there, you know, the typical treatment doctors are oncologists like myself and we more or less specialize in medical treatment or medicines. Surgeons, which in this case are urologists, so they specialize in surgery or different forms of treatment to the prostate. And radiation oncologists who either put in or shoot in radiation. So those are the typical main three modalities. I would say that for a newly diagnosed patient, the other two modalities, which are quite important are the pathologists. So number one, making the diagnosis, but as we just discussed, really it's important to have a subspecialized pathologist to really look at the biopsy and give that detail information about prognosis, that really guides our treatment recommendations. 

And then a radiologist. Sometimes the MRIs can be a little bit difficult to read. So someone that is sub-specialized within radiology that has really looked at a lot of different prostate images can be quite helpful. And in today's era, we have a approved and available as well as emerging different types of, we call it molecular imaging or PET scans that are coming into the pool. So those are the main kind of five different specialties that we would say go into a multidisciplinary team. As important are the patient's primary care physicians and or other sub-specialists. Because as I talked to individual patients, there's really three things that really drive their treatment recommendations decision. One is the prostate cancer, how worrisome or not worrisome is that, their overall health, and optimizing their overall care. Because as we mentioned before, prostate cancer sometimes sits there for a long period of time.

So it's important to know how long we expect that patient to live otherwise. And then choices is the third, so the patient and his family and support group is quite important. And then there's a number of different ancillary services. I don't mean that they're not important, but those, depending on the [inaudible 13:31], sometimes those are dietitians, sometimes they are acupuncturists, sometimes they're physical therapists. Sometimes as we deal with either problems because of the tumor or complications from therapy, we deal with sexual dysfunction and we have specialists for that as well as urinary issues. And those can go on and on, but I do think it's important to have all of those different specialties at ones disposal.

Host: So the two main modalities, it seems to me that most patients with localized disease will be choosing between relate to surgery and radiation, is that a fair assessment? And maybe you can just give us a quick summary of kind of the pros and cons of who might choose one versus another of those. And what other factors figure into that.

Dr. Tagawa: We generally lump the prognosis of an individual prostate tumor into three groups. Sometimes it's four, but the very low risk are those that we think are not going to grow for 50, a hundred years. And generally the patients don't have that much to live. So we generally advise active surveillance for them. So it's watching very closely, but actively to make sure they're not one of those rare cases that actually grows despite us really predicting that nothing's going to happen. So though all of us might be involved, but none of us is really doing so much in terms of treatment, when we get into the intermediate high risk, that is where it's more and more common to have two or three different types of treatments at the same time. So you're right, that generally the main modality of treatment for someone with intermediate or high risk prostate cancers, either surgery or radiation. Generally speaking for an average person or for a group of men, there's no difference in terms of long-term curate with either type of therapy.

However, there are individual patient or tumor characteristics sometimes will push us one way or the other, but generally speaking, it's one or the other. And then sometimes, either one is combined with the other in either order. So some men will start off with surgery and have radiation, some will start off radiation and have surgery or some other therapy to the radiated prostate. Generally speaking that second treatment is there, if there is residual cancer following the first one or recurrence of the cancer following the first one, and we can talk about that later as this cancer does have a pretty sensitive blood test in PSA. And then in addition to either one of those two is systemic therapy or medical therapy. Generally speaking, that comes in the form of hormonal therapy, which is probably more accurately termed anti-hormone therapy. So generally a therapy that's aimed against the male hormone testosterone. So drugs that will either decrease the level of testosterone in a man's blood or block testosterone that is there. And that is sometimes combined with one of the other therapies, especially with radiation.

Host: So a patient who's choosing amongst those modalities. I mean, what are the sorts of things that figure into that? If they need an intervention, as you see a patient, is it solely around the age and the risk of the disease? Are there other factors that figure into that, is it the side effect profile, what informs those sorts of decisions?

Dr. Tagawa: So for many men, it comes to them and their family. And a lot of times it's based on whatever their own kind of historical biases are thinking about different things. But a lot of times it does come down to side effects and what is more tolerable to them because, there are many more men that are diagnosed than actually ever die of disease. And that's in part because we cure most men or at least we treat the cancer for long enough that they end up dying of whatever they're going to die of, if they were never diagnosed with prostate cancer. So the side effect profile is quite important in terms of treatment choices. That being said, it's not that it's a hundred percent to the patient to have to decide, or the family has to decide because there are some things that guide us. 

So the size of the prostate, the location of tumor the presence or absence of urinary symptoms coming into the diagnosis will help guide us either towards or away from radiation. For instance, so we can guide some patients in that way. And then also, you know, what has happened in the past in terms of their pelvis or their urinary system, have they had some other diagnosis that involves surgery or some other diagnosis that involved radiation in the area. So those are rare cases but certainly will be influential if they have happened before.

Host: So how are patients typically followed when they've had their quote unquote primary therapy and are in remission, whether it's observation, whether it's surgery, whether it's radiation, kind of what's the usual course recognizing that I, as you stated, I presume most patients are not likely to have a recurrence, but some might. And so they need to continue to be followed, correct?

Dr. Tagawa: That's correct. So those that have either choose to have, have treatment even with very low risk disease, or we encourage to have treatment because of intermediate or higher risk disease, like other treatments, we follow them for two reasons. One is to see if their cancer has recurred. And secondly, to make sure that any side effects they have ongoing either get better or don't happen late. So we're looking for the, both of those, but in terms of the cancer itself, this is a cancer that does have a very sensitive blood test in PSA. So, Oh, but the vast majority of prostate cancers are driven by the [inaudible] pathway, which is a fancy term for hormones. And when that is there either cancer or residual prostate tissue, that's not cancer makes PSA. So following treatment, it should be lower than it was at the beginning.

And if everything was gone, meaning both the prostate cancer, as well as the normal prostate is gone, it should be basically zero. So we call that undetectable. And if the prostate just been radiated, there's some normal tissue left, it should be some low number and we follow them, you know, at the beginning more closely, and then less with time. And overall, when we look at worldwide numbers, the US system might be a little bit better, but it's somewhere between one in four, to one in three, we'll have what we call by a couple core recurrence, which means that they get treated. We think it's gone, but at some point, the PSA rises that is more or less a reset where there's some patients that will have very low risk recurrence, some will almost higher risk recurrence, but it's also reset in terms of looking at things. So we will think about scanning them to see if we can find anything. The vast majority of cases we cannot, even when the PSA goes up fairly substantially, at least in terms of how the doctors and the patients think about it.

Luckily what's maybe we can do one of these in another year, as I expect to have what is considered actually standard of care in other countries, but what is not available in the United States, I expect to have a couple of very sensitive types of PET imaging, something we call PSMA PET imaging, which can tick up locations of tumors. So the most common question that I will get is where is my PSA coming from in that situation? And generally speaking, we'll say probably where the prostate was, or it was treated, because that's the best educated guess, but now we have these more sensitive imaging modalities to be able to pick up where is it coming from. To reset things, you know, we assess the risk based largely upon how fast is PSA rising and what is the absolute level. We may get an image to see if we can see it, but really the thought process is, is there something left where the prostate used to be or was treated or is it somewhere else?

And the main reason for that is because we can cure men if the recurrence is what we call local. So where the prostate used to be in the case of surgery or with the prostate there just some residual cells that are in the radiated prostate, or the ablated prostate, if they had something else. Kind of the simple way of thinking about we do the opposite for what was done at the beginning. So if they had surgery with radiation, if they had radiation, we look at surgery. The term salvage therapies some people don't like that word, but in this case, I think it was a positive if the first treatment did not cure them, we're looking to salvage the cure. So the intent of whatever we're going to do in that situation is looking to cure them.

Host: So in a scenario where the recurrence is not local, whether it's biochemical or whether it's detectable, biochemical only, or detectable in one or many sites, what is the typical approach for these patients? And I know a lot of your focus is on new drugs and new approaches for this group of patients, how are they typically managed both with standard therapies and some of the things on the horizon?

Dr. Tagawa: So the most standard therapy is what I mentioned before. It's hormonal therapy. It's usually termed something we call ADT, which stands for androgen deprivation therapy. Which, it's most commonly injections, which shut down the man's production of testosterone. Testosterone is generally seen as the food for cancer, at least prostate cancer. And when we take away the food, most of the cancer either dies or goes asleep. So that's been the traditional therapy. What's nice about that therapy, should there be a recurrence of prostate cancer, is that it works virtually all the time, working, meaning killing some of the cells and putting the rest of the sleep and PSA going down. So that's, what's nice about that. What's not nice about that is there are some side effects and at least the traditional form of therapy we know is not curative. So there's a couple of directions where we're going.

One is, as I mentioned before, more sensitive imaging modalities where we can find where the PSA is coming from, rather than just blindly taking care of where the prostate used to be. And we see an extra spot or two, we might be able to surgically remove that or radiate those spots. And maybe those men who weren't going to be cured by just treating the prostate area would be cured. And simultaneously we're looking at new drugs, most commonly in this situation, we're taking drugs that we know already work. So, men with at least as of right now, incurable disease, so cancer all over their body. And we give these powerful medicines that can't get rid of billions of cells, but if there's hundreds or thousands with just PSA, we might be able to bring those into the situation and cure men. Or if not cure the men that at least give them a lot longer before something happens like the PSA going back up or the needing a new line of therapy like chemotherapy. So those are happening more or less simultaneously.

Host: So what are some of the new drugs that you think people who are dealing with prostate cancer audit either know about, or keep an eye on as they think about the future of this therapy or what may be needed in the course of a patient's dealing with prostate cancer?

Dr. Tagawa: So, as I mentioned, the backbone of our therapy is hormonal and much of what we've had until very recently have been add-ons or kind of typical what we call cytotoxic chemotherapy, which is poisons that luckily poison the cancer much more than the patient. Although we figured out actually at this institution, how those work actually against the hormonal pathway in prostate cancer. Two drugs were approved, they fall into the class of what we call PARP inhibitors. And as a kind of the generic that I mentioned to a patient is we give these drugs to a random person with prostate cancer, highly unlikely to work.

However if we give these drugs to someone with certain genes, either inherited or in the tumor, then there's a high chance of working. So the bottom line is if we never test the no patient is really going to be eligible for this it's to test. And that can be done either with a biopsy or a blood test, the other set of drugs that we don't know this yet, there was another type of a drug that came out that is kind of related to a pathway that was discovered by our Kempson director. So I'm not going to get into great details, but when tumors develop resistance to the typical hormone pathways, they're different pathways. One of them is called PF3 kinase, ones called AKT, but they're kind of ways that tumors learn how to become smarter and get around this. And what we learned from a press release is that there's a drug when we add it to hormonal therapy, it works better than just that hormone therapy alone.

However, again, only in tumors that have a specific genomic alterations, it goes back to us importantly, getting a sample of that man's tumor and testing it before we embark on a therapeutic pathway. One of the other ones, which is in the realm of targeted therapy that I mentioned briefly before, at least in terms of the target is called PSMA. So all men that have been afflicted with prostate cancer know what that is. We just stick in the word M for membranes, the PSA is made inside cells and goes in the blood PSMA membrane. It's stuck to the cell. So it doesn't go into the blood. So it's attached there in terms of the target. I think of that as a lock that's on those specific cells, we can engineer keys and attach things to those keys. So we inject something into the blood it'll circulate until it finds those very specific locks that for the most part are only on the prostate cancer cells. And then we can treat those cells.

And one of the nice things about this target therapy is rather than it being there only depending on what target, you're looking at, one in five or something like that, this is more like in nine and 10. And we can also evaluate this in a noninvasive way with the scan that I mentioned, the PSMA scan. So we don't yet have an approved therapy against this target, but we have had a randomized trial that was positive. And there's another randomized trial that we expect to have results on in the next couple of months. So I think that's yet another target that is ripe to lead to improvements in outcomes for patients, meaning delay in time for cancer growth delay in time to death, and hopefully making patients feel better.

Host: So it sounds like there's a lot new happening in prostate cancer. What message would you have for our audience? If one is a patient either diagnosed initially with prostate cancer or having a relapse, what are the one or two things that people should be sure to keep in mind as they try to sort through their situation?

Dr. Tagawa: I think anytime there's a diagnosis of a individual or his family or support system, you know, it can be quite tragic and anxiety provoking. So what I've mentioned, even if someone walked in the door with cancer that has spread to literally a hundred places in his body, there are very good treatments. So this is one of the cancers that we can relatively easily turn into a chronic disease. But in fact, most men, luckily are in a more curative situation when they walk in the door. To obtain the best results my suggestion is to seek out opinions. So that could be multiple opinions at one place. So kind of one stop shopping. If someone is in an institution that has a good multidisciplinary team, which can include the five different specialists I mentioned, plus primary care, cardiology, etcetera, under one roof. I think that makes things easier on the patient any way to seek out opinions from all the different subspecialties in order to get the most accurate diagnosis and prognosis that comes out of it. And those two together lead to I think, the best treatment recommendations.

Host: So before we wrap up, I just want to ask you briefly about clinical trials, your role here at Weill Cornell and New York Presbyterian is focused in part on organizing and supporting our clinical trials activities. Some of the things you talked about as far as new advances are either available through or were developed through clinical trials and of what's the message for patients as far as learning about and participating in clinical trials, whether they're dealing with prostate cancer or some other sort of serious illness or cancer diagnosis?

Dr. Tagawa: One thing that we really make almost all of our medical events is through research. And a lot of that, or most of that is it's with humans and patients is through clinical trials. The other, that clinical trials are not necessarily last resort. So it is true that I will see some patients that will come to me, they've had all the therapies that their doctor has, can think of and they come to me and they enroll in the clinical trial, which hopefully will help them as well as other people in the future. But it's not only in that situation. So we have another place that has clinical trials for virtually every single situation. So someone walks in the door with the most typical situation, such as a PSA that led to a biopsy that says, okay, there's this intermediate risk prostate cancer. There are a number of different clinical trials for that situation as well.

That might be helpful either diagnostically giving additional information, how to have a guide treatment and, or investigating new treatments to make treatment better for the individual men. And hopefully for that man in the future, as we're talking about prostate cancer, but generally speaking for other cancers as well. So my suggestion is someone with cancer that's newly diagnosed or has had cancer for a while that has grown recently, talk to your doctor. And if it's not brought up, say what about a clinical trial? You know, I think a good doctor will either have clinical trial available and or know how to refer for them, and may not be right for every single individual every single time, but I'm not bringing that up will shut the door to that opportunity.

Host: Well, thanks very much, Dr. Tagawa. This has been a great discussion and a lot of good insights for our audience around not only prostate cancer, but clinical trials in cancer in general. So thank you. I want to invite our audience to download, subscribe, rate, and review Cancer Cast on Apple Podcasts, Google Play Music or online at weillcornell.org. We also encourage you to write to us at cancercastatmeddotcornell.edu, with questions, comments, and topics. You'd like to see us cover more in depth in the future. That's it for Cancer Cast, conversations about new developments in medicine, cancer care, and research. I'm Dr. John Leonard, thanks for tuning in.