Cancer ABCs From Surviving To Thriving - How to Thrive with Cancer

Learning About Oligometastatic and Metastatic Prostate Cancer and How Cancer Metastasizes

May 23, 2019 Dr. Ken Pienta (The Johns Hopkins Hospital) and Joel T. Nowak (Cancer ABCs)
Cancer ABCs From Surviving To Thriving - How to Thrive with Cancer
Learning About Oligometastatic and Metastatic Prostate Cancer and How Cancer Metastasizes
Show Notes Transcript

Dr. Ken Pienta from The Johns Hopkins Hospital explains all about metastatic prostate Written Transcript at: and how it spreads or metastasizes.  

He Includes in his discussion how prostate cancer is staged, how cancer migrates from the prostate gland to distant sites that can then develop into tumors.  In this discussion He clarifies the  difference between local invasion and metastatic disease.  

He also talks about the current reality of our scanning technology, including the  new Axumin and PSMA scans and how large, or how many cells, need to be present in a tumor in order for it to be visualized.  

Dr. Pienta describes the current treatment issues surrounding oligometastatic prostate cancer (just a few tumors in the pelvic area) as well as the role of the tumor micro-environment in supporting the metastatic process.  

He also shared two clinical trials, the TED1 and the TED2 Trials (Total Obliteration Disease Trials) which he is conducting for newly diagnosed men with five or less metastatic lesions.     

Support the show

Dr. Kenneth Pienta: Once a man has metastatic disease, we currently cannot offer to treat that patient for cure. In fact, it's true for all cancers from all organs.


Joel Nowak: Today, we are lucky to be joined by Dr. Kenneth Pienta. Dr. Pienta is a professor of Medical Oncology. He is the Donald S. Coffey professor of Urology, and also a professor of pharmacology and molecular Sciences at the Johns Hopkins Hospital in Baltimore, Maryland. Dr. Pienta is an expert on prostate cancer tumor development, as well as in the tumor micro-environment and how it inter-acts with the development of metastatic or advanced prostate cancer, which is the type of cancer that actually kills men. 

First, will you please explain what is metastatic prostate cancer?


Kenneth: Metastatic prostate cancer and metastatic cancer of any kind is when the cancer cells have left the primary site where they first were formed. So, in the prostate cancer that’s the prostate. You have metastatic disease if those cancer cells are found in lymph nodes or in bone or in any other place in the body that is not of direct spreading outside of the prostate. 

For example, if a cancer cell walks out of the prostate itself and moves up into the seminal vesicle, which is right next to the prostate, that's not considered metastatic disease. That's considered local invasion. But if that prostate cancer cell moves farther away to somewhere that is not directly touching the prostate, that's considered metastatic disease.


Joel: I see and actually, that's an interesting comment. I know that for a lot of people that's actually confusing. Why if it's left the prostate gland, even though we'd say it would be in the seminal vesicles, why is it not considered a metastatic spread? 


Kenneth: When we talk about cancer spreading, we consider that it's spreading in one of two ways. It can spread locally, which means it's literally growing out of the prostate and the next thing it touches like the seminal vesicle or it could go to the fat around the prostate. That's what we call locally invasive. 

And when we're staging cancer, we talk about the TNM system or tumor node metastasis system, when a cancer is growing bigger and bigger, we refer to that as part of the T or tumor, meaning what size did it get to what did it locally invade. If it moves through the lymphatics up into a node, then we call it nodal disease. If it's nearby the prostate and if it goes farther, then we use the M stage or meta static terminology. 

Technically once a cell gets past a,  contiguous structure, a structure that's touching the prostate itself. So even those nearby lymph nodes, that is now we're calling it metastatic. We break that down and cancer between nodes and distant metastasis, like to bone simply to help us with the prognosis and staging. Once you've moved past the area where you're actually touching the primary organ, it's considered metastasis. 


Joel: That's really interesting and I thank you for explaining that. Because I know for a lot of men, it's confusing and it's actually become more confusing with the new drug Erleada, which is designed to treat men with M0 disease. If you looked at the clinical trials, and I'm sure you're aware of this, though they classify it as M0, meaning no metastatic disease, if I understand it correctly, they allow it in the clinical trial for a number of smaller lymph nodes in the pelvis area, and they still defined it as M0. That adds to the confusion. I'm wondering if you have any thoughts on that? 


Kenneth: I do have thoughts about that. I think the confusion around M0 is because M0 is a term that refers to somebody who we know has cancer generally in the biochemical recurrence space, so you've had your primary therapy with surgery or radiation and now you have a PSA going up. That's called a biochemical recurrence. Well, if we do a bone scan or a CT scan at that time and see a spot, we think there's cancer there, you're labeled as M1, meaning you’re metastatic, but if we use a scan and don't see any cancer, you're labeled M0, but we know the cancer's there it's just too small to see. 

One of the places where this has become very interesting is with the advent of more sensitive imaging like the Axumin scan or the PSMA scans, more and more patients who were M0 by conventional imaging, bone scan or CT scan or MRI are now becoming M1 or metastatic because we can see it by PSMA scan or Axumin scan, which will pick up say, a three millimeter lymph node, which a CT scan can’t. The confusion for patients is when you say M0, they have no metastases they have that's not true. They have no detectable metastases by current imaging, but we know it's there somewhere.


Joel: Why do we label it that way? Labels should, in this case or construct should clarify, and it doesn't seem to do that. 


Kenneth: I think in medicine is always evolving, but we've had bone scans and CT scans of the abdomen and pelvis and chest for over 20 years. We've used these tests as the standards of care for patients with cancer for the last 20 years. 

We needed to label people somehow, because these were the tests and they were stable across time was easy to say, “Oh you have metastatic disease we can see. And we call that M1.” or “You have Metastatic disease, we can't see and we call that M0.” 

For the medical profession, it was a very standard way to refer to these, that state of not being able to see anything on these very stable scans across time, we could have said metastatic unknown like MU instead of M0, we're using a number of classification. It just fell into practice to use M0 and only recently now with the better imaging modalities, are we running into this issue that M0 is actually a moving target or M1 is a moving target based on the types of scans that you have.


Joel: It's interesting and confusing, and I appreciate the clarification. So, what do we actually know about how and why cancer in this case prostate cancer becomes metastatic?


Kenneth: I wish I knew. 


Joel: [laughs]


Kenneth: We know that prostate cancer becomes metastatic because number one, prostate cancer cells leave the prostate and they can do that basically through three avenues. 

One avenue is that as the cancer is growing inside the prostate, it hits a blood vessel and the prostate cancer cell can basically fall into or walk into the blood vessel and be transported out of the prostate to a distant sight. 

The second way a prostate cancer cell can leave is actually through the lymphatics. The lymphatics are a system of highways throughout your body that parallel your blood supply in your nerves that allow your immune cells like your T cells and your macrophages to help fight infection and clear extra fluid. The lymphatic system is one of the most understudied systems in the body. But it is well known that cancer cells walk up the lymphatic system or get drained by the lymphatics and sit in lymph nodes which are sort of wait stations for usually for your immune system to help fight infection. When a lymph node gets in large it's because you're fighting an infection or your head cancer cells grow there. All your lymph nodes and lymphatics actually drain up into a major lymphatic vessels called the thoracic ducked up in your chest and that dumps into the vena cava and then goes through the heart into the blood supply. 

The third way out, we now know that prostate cancer cells can travel up nerves. Once they're out that way they get either into lymphatic or the blood ultimately to test the size to bone, which is what prostate likes to do. You have to end up in the blood at some point. 


Joel: That's really scary hearing the whole picture. I'm going to come back to that a little bit later, but if a man is told, based on scans that they have developed metastatic disease, what is the actual significance of that for a man for his prognosis?


Kenneth: I think that what we know, unfortunately, is that once a man has metastatic disease, we currently cannot offer to treat that patient for cure. We do not have a curative therapy for metastatic prostate cancer. In fact, it's true for all cancers from all the organs and whether it be colon or liver or lung or bladder or ovary or breast. 

Once a person has metastatic cancer, we can't cure them with any known medicines, except in some rare cases with immunotherapy, which we can get back to, but unfortunately what it means for a man with prostate cancer is that we are moving from a curative paradigm where they may only have cancer in their prostate and we're going to treat that, to a we're going to manage your disease paradigm. We're going to keep this cancer in check with multiple different modalities until we can't anymore. 


Joel: I know that you treat many patients in clinic, are patients who are metastatic, do you assume automatically that the cancer is going to kill them?


Kenneth: I tell my guys that if they have metastatic cancer, more likely than not, this cancer will kill them at some point.


Joel: What do you mean by at some point? You have patients who had a long survival despite being metastatic, or is it something that, as some doctors say you should “get your affairs in order?”


Kenneth: Well, I think we all have patients who do well and we all have patients who do average and we all have patients who do poorly. Every cancer, including prostate cancer has a average survival time. 

Like if you're diagnosed with metastatic disease, you have, on average, if you take 100 guys, where are 50 of them still alive, that's called the median survival and that's what you see most often quoted. In fact, in every clinical trial, where they're trying to help guys live longer, you're trying to beat a median survival time where half the guys have any treatment have lived longer than the other guys in the other arm. 

We all know for prostate cancer, what the median survival is, if you are diagnosed with metastatic disease. Guys can do better than that or worse than that but there's an average or median. 

The other thing that's interesting now, though, that we know from recent studies that have looked at, guys with lesser tumor burden like that M0 population with Erleada, or if you look at the studies like LATITUDE or CHARRTED, survival at diagnosis and treatment depends a lot on how many distant sites you have of cancer, how many metastatic sites you have. 

If you are diagnosed with less than three, for example, spots on bone scan, your median survival is very different than if you're diagnosed with six. Now what we're learning and we didn't know how to do this even two years ago, we can talk about survival for guys based on how much disease they have at the diagnosis of metastasis. 


Joel: Does this specific the site that the metastasis has developed, does that have any significance for survival?


Kenneth: Yes, anybody who develops metastases in what we call a visceral organ like the lung or the liver do more poorly. We also know you do more poorly if you develop metastasis in the bone, if it's outside the vertebral column or the pelvis. Guys who develop like a rib metastasis, in general do poor than a guy who say, has a metastasis to their L-spine.


Joel: There's another term that gets thrown around periodically. That's Oligometastatic prostate cancer. What is that?


Kenneth: Oligometastatic disease is really defining what we call low volume prostate cancer. It is a man who's diagnosed with generally depending on who's defining it less than four or less than five metastatic lesions when we image them. A guy with three spots on their bone scan is considered to be Oligometastatic. A guy with six spots is considered metastatic. It's really a numbers game. 

Now what's really interesting about the whole concept of Oligometastases, and what is still very controversial.  Oligometastases were first described about 30 years ago by Hellman and Westelbalm, they postulated that someone with cancer could have a lesion developed, that's metastatic that escaped the primary tumor at a very early time and it wasn't quite as malignant as one that might escape later and so that tumor itself that metastases might be what we would call an evolutionary dead end. That by treating that with that metastatic spot, you could actually potentially cure a patient with metastatic disease. 

What we've learned and what most people have moved away from that concept, but there are multiple trials going on right now as well as multiple folks are treating Oligometastatic prostate cancer to at least intervene in the disease process. Maybe not cure somebody, but certainly by basically playing whack a mole is to buy again more time to manage the disease to knock out fishing kill billions of cancer cells with by spot radiating that can only help the patient and so the whole treatment of Oligometastatic disease was revolutionized within the last three years because of those concepts, but also because of the ability to use the cyberknife or other radiation equipment to safely deliver radiation very carefully with little toxicity to these small spots of cancer. 

A lot of work remains to be done but the whole concept of treating Oligometastatic disease is now a very common one in prostate cancer. 


Joel: I think that terminology that's often used for that would be debulking. Is that correct? Or debulking the tumor?


Kenneth: That’s one way to put it, yeah.


Joel: It actually adds some confusion because oftentimes men who are diagnosed with prostate cancer and they go in and say, to have surgery, and we hear about the doctor opening them up and closing them and not removing the prostate gland because they see that the cancer has spread outside of the gland, but based on what you're saying about the concept of debulking, shouldn't that gland still be removed? 


Kenneth: The concept of removing the primary in patients who have Oligometastatic or metastatic disease is a very, very controversial one. I personally have a trial, a clinical trial in this space, where if I have a gentleman who's newly diagnosed with 

Oligometastatic disease, and we define that as five metastases or fewer on conventional imaging, what we do for those gentlemen is give them chemotherapy and hormone therapy for three months. We then remove their prostate to debulk the primary tumors, and then we actually do radiation to those individual metastases as a way to try and cure these guys who are considered incurable. 


There are multiple trials like that ongoing right now, there was a recent trial that was reported out of England where patients with a metastatic disease did have their primary tumor irradiated, not taken out but radiated, which showed a potential survival benefit but the numbers were small. But I can tell you there are multiple clinical trials going on right now to try to answer this question of whether debulking makes sense. 

I can tell you, 10 years ago, nobody thought it made sense. Now the field is much more split about whether it would make sense or not and that's why we're trying to do these kinds of studies. And in the meantime, with every patient who presents with Oligometastatic or metastatic disease, we have a discussion with them about whether they want to treat their primary tumor or not.


Joel: Specific to the trial that you just mentioned, are you still in the process of recruiting men for it? 


Kenneth: Yes, we are recruiting still men for that trial. 


Joel: I'm going to suggest if you could just briefly describe what the criteria would be for somebody, and then if someone might be interested in following up with your office, they can always send me an email and I will make sure that the information is forwarded over to you if that would be okay.


Kenneth: Sure. We have two trials ongoing right now and they’re on We call them the TED-1 and TED-2 trials. So, Ted stands for total eradication of disease. 

If a gentleman is diagnosed with oligometastatic prostate cancer meaning less than, again five metastases on bone scan or CT scan, we enroll them give them three months of chemotherapy with Docetaxel plus Lupron plus as a LHRH agonist plus Abiraterone as a super hormonal agent to maximally shrink their disease. We then have them go to the operating room and have their prostate and lymph nodes removed, and then we radiate those distant sights of disease with thought radiation with a cyberknife type of radiation. 

If a patient also has surgery and positive lymph nodes, or a positive margin, we actually give them salvage radiation like you typically would in that setting. And so that's the TED-1 trial, the TED-2 trial is actually for patients who have gone to surgery and unexpectedly are now found to have nodal disease or positive lymph nodes finding out at the time of surgery that they actually had metastatic disease. And in that setting, we give the chemo hormonal therapy between surgery and radiation.


Joel: If anyone is interested in following up on this, you can go to or if you send me an email, I will make sure you get the information. 


Dr. Pienta, one of the things that would be helpful because sometimes people don't understand it and I hear about this again and again, that men who do receive primary treatments and they're told that "they've been cured." A statement I think never should be made, but often it is per term such as "We've got it all." Yet we know that at least 30% if not more of these quote "cured men" end up having a re-occurrence where they find out that the cancer actually has spread to other parts of their body and has developed into some sort of metastatic disease. So if the glands been removed, and if they've been cured, how can this possibly happen?


Kenneth: Well, that happened because the prostate cancer cells escaped the prostate through one of those avenues that we talked about earlier before the surgery ever happened. They were either lying dormant somewhere or they were growing so slowly that again, we couldn't find them by conventional imaging. 


What's really scary is to see cancer in the lymph node that has to be that lymph node on the CT scan has to be about a centimeter in size, which is about the size of your index finger nail that is a billion cancer cells, a billion. So you can have literally 100 million cancer cells or 10 million cancer cells, sitting somewhere like in a lymph node. We'll never know, we'll never see them. So if you had a prostate cancer cell that escaped several years before and is sitting there growing somewhere else, unless you have a billion of them, we can't see them. It's a very scary and sobering thought.


Joel: It certainly is. You touch briefly earlier on about the newer scans; the PSMA and the Axumin scans. We know that these scans are more sensitive, and I assume that that means that they will pick up a metastasis that are smaller or have less than a billion cells, or are we talking about a billion cells with these particular scans.


Kenneth: So, a PSMA scan has the sensitivity to pick up anywhere between a two millimeter to three-millimeter bit of cancer, which is you know is about a quarter of an inch. It's a big improvement over conventional imaging because of the imaging tells you it's prostate cancer sitting there. The reality though, is that that's still anywhere between 10 and 25 million cancer cells, even with the best imaging. 


Joel: Is there any way to know how long a cancer cell has been outside of a man's prostate gland? 


Kenneth: No, unfortunately, there is not. 


Joel: So, from the time a cell is released till the time it's large enough to be scanned, is there any assumption as to how long that process takes? 


Kenneth: Say that to me again?


Joel: So, from the time that a cancer cell escapes the gland, until the time it finds a place to live and takes up housekeeping so to speak, and grows to be large enough to be seen on a scan. What's the timing on that? 


Kenneth: Yeah, unfortunately, we don't know. This is something I've spent my entire life trying to study because we don't know if a cancer cell gets to a distant spot and lays dormant or hibernates there for years before it wakes up and starts to divide and proliferate, or if it gets to a distant spot and simply starts to divide two cells to four cells to eight cells, but very slowly. 


We can't tell the difference when we see a spot for the first time. We don't know if somebody's cancer cells been sitting there and all of a sudden is growing rapidly or was growing slowly across the entire time. The field of cancer research is very split about that and how it happens. 


Joel: Does PSA doubling time have anything to do with being able to judge how quickly the tumor itself is growing. 


Kenneth: PSA doubling time in general, very broadly, does have some sense of how fast the cancer is growing. Cancer growing is always a balance of cancer cells proliferating and dividing, as well as cancer cells dying. So the PSA doubling time gives you a sense of how fast that balance is occurring and clearly if you see a PSA that's doubling less than every six months, that tends to be a more aggressive cancer. 


A lot of doubling times are greater than a year and that would suggest the slow doubling time, but we don't know what happens in that range where the PSA is still undetectable. We don't know what was happening below that threshold. And again generally, we've always used the idea that PSA of four, and this is only in the broadest terms, is equal to about a centimeter tumor, which is about a billion cancer cells. If you say PSA of .4 is 10% of that, it's 10 million cancer cells, or 100 million cancer cells, .04 is 1 million. We lose the numbers there. We can't do it like that. Wish we could. So we don't know what's happening in those areas where there's just less cancer cells than we can measure the PSA, and once we start to measure the PSA it's not direct comparison. So we have to be very careful about any kind of conclusions we draw in that space. 


Joel: You mentioned dormancy. Is that something that all cancer as it spreads will do? What makes a cancer cell dormant and what wakes it up? Do we have any idea? 


Kenneth: I wish we did. We don't know what causes a cancer cell to lay dormant or hibernate, or wake it up. We have some recent clues. When we really use the word dormant, what we mean is that it's not dividing. 


Almost every cell in your body by that definition is dormant. A liver cell isn't dividing normally. You're at homeostasis. Your kidney cells aren't dividing. Your nerve cells aren't dividing. Your colon cells are. The lining of your gut is but the majority of your cells in your body are not dividing. They're "dormant." But that doesn't mean they're not functioning going about their activities of daily living. 


We think that a cancer cell to metastasize or spread has to be dormant, it can't be actively dividing. It can't be using its energy to divide. It has to be using its energy to move and get enough nutrients to survive. So, we think a cell that's spreading is actually already dormant. And then when it gets to say the bone and going to set up shop there, at some point, it will decide that it has enough food and oxygen where it's not stressed by its environment and actually can start to divide and proliferate at that point and come out of dormancy. We think it's related to how stressed the cancer cell is, as far as when it turns on and off.


Joel: Is there a way we can control the stress that a cancer cell may undergo?


Kenneth: In the lab in a mouse, but we haven't figured out how to do that in people.


Joel: A lot of people believe in things like changing the acidity of the body. 


Kenneth: Right.


Joel: I'm not convinced that you can actually do that. But, assuming you can put stress on tumor cell, is there any validity to anything like that? 


Kenneth: Well, we just don't know. I think that when folks talk about acidity, they talk about glucose, they talk about pH, they talk about other nutrients, they talk about vitamins, we don't know anything really definitively about those different things. But what we do know for example, is that inflammation associated with for example, obesity helps tumors grow and I think there's a lot of work on going about if you can take a guy who is, for example, extremely overweight and help them bring their weight under control that may help them live longer and help their cancer not grow as fast. 


There's a lot of data around anti inflammatories, suggesting that again, if you can cut down bad body inflammation, you might be able to change the trajectory of cancer growing. 


I don't think, well, there are some people that believe it, but most people would say that might help. It's not going to cure somebody with metastatic disease, but you can potentially modulate how fast the cancer is growing. 


I can tell you that everyone that we treat, especially with hormonal therapy, we actually now prospectively put them on pretty rigorous diet and exercise plans, specifically to help them not gain weight as a side effect of the LHRH drug, the Lupron which slows metabolism down, but also to try and cut down inflammation. 


Joel: Over the last 10 years, we've heard a lot about the significance of the underlying genetics of cancer; how important knowing your genetics and the genetics are in the cancer as it develops. There must be other issues or factors that contribute to the aggressiveness of cancer and its ability to metastasize. Is that the case and what would these factors be?


Kenneth: Well, unfortunately, Joel, we don't know what those factors might be. We know that some genes predispose or changes in genes predispose folks to cancer and prostate cancer. We're developing some therapies around knowing what those defects are, or those mutations are. We currently don't know of any gene for example, that-- 


[inaudible] [background music plays]


Kenneth: -help you develop cancer; we know what genes can, for example, be targeted by a drug. But we don't know specifically what genes make your cancer worse or better. 


Joel: I know you've done a lot of work in the tumor micro-environment. Could you tell us what that is and how the tumor micro-environment interrelates with the cancer? 


Kenneth: Yeah, the old way of thinking of cancer was that it was just a bunch of cancer cells growing that attracted new blood supply and grew even bigger. We now know that cancer cells live and grow inside an ecosystem. They're interacting with other host cells, those cells of the patient; blood vessel cells, T cells, macrophages, fibroblasts, all the cells that are part of the normal body. They're all interacting together and that interplay, the ecosystem they create, is called the tumor micro-environment. 


We call it the micro-environment because simply it's small, it's inside a organ or it's in best visualized, often under a microscope. The best way to think about it is that cancer is not interacting alone with itself. It's interacting with the body all the time. 


We actually use the ecology and ecologic principles to describe that and understand that; how a cancer cell is interacting with the body to unfortunately, keep growing and dividing and eventually spreading. 


Joel: I see. Just as we're getting near the end, I was just curious as to what you see for the future of prostate cancer treatment. 


Kenneth: It's an unbelievably exciting time for all of us in the treatment community as more and more therapies come online to help guys with metastatic cancer live longer. 


I think the big disappointment over the last few years has been the fact that immunotherapy is the checkpoint inhibitors that work so well in other diseases like melanoma and kidney cancer and now even bladder cancer, don't work in prostate cancer. 


And the real question is why? Why do these therapies that works so well in melanoma, for example, don't work in prostate cancer? There are several theories about that, including the micro-environment of a prostate tumor is very different than the micro-environment of say a kidney cancer or melanoma, and where the T cells which are the cells that are the hunter killers that come in and wipe out cancer cells when immunotherapy works, are being actively kept out of the prostate cancer. 


That's this whole concept in science called an immune desert. In other words, when the pathologists look under the microscope, they can't find the T cells in the prostate cancer like they can and other cancers. 


Another idea is that the T cells that do get in are held in check by different molecules than the checkpoint inhibitors that are approved. We may need different checkpoint inhibitor drugs in prostate cancer. So, a lot of work is being done to try and figure out why immune therapy does not work in prostate cancer. 


I think we're going to crack that nut to some degree over the next few years, leading to new therapies in the immune space. 


I also think, quite frankly, the United States now is going to catch up to the rest of the world in using PSMA guided radioligand therapy. As you know, in Germany and Australia and several other countries, we can use PSMA attached to a radioactive bomb like Lutetium 177 or Actinium, to deliver radiation dose right to the prostate cancer no matter where it's sitting in the body. 


So that therapies have been developed for many years overseas and now we're starting to see multiple clinical trials being utilized in the US to learn how to use those therapies best and in what combination. As a single agent, I don't think they're curing very many people, but they certainly do help people live longer. 

So, I think in the near term, you're going to see a lot more PSMA radioligand directed therapy coming to the fore. 


Joel: Only about 80% of men with prostate cancer actually generate PSMA. So that kind of still leaves that other 20% hanging but I think you're right, these things are exciting. 


I know a lot of our therapies that we have now are really hormonally-based. All of them for the most part other than the radiation-based ones. Are there any other things that you are kind of aware of that may become important for prostate cancer, because there seems to be a desert other than radiation and hormonally-based treatments. 


Kenneth: So, I agree with that. The other place that we're seeing a lot of activity is around those genetic mutations like BRACA to, to try and understand where the PARP inhibitors are going to work and what combination they're going to work in. There is some evidence for example, that a PARP inhibitor sequence with a checkpoint inhibitor may be better. 


So, there are a lot of clinical trials ongoing right now and we still don't understand what are the newer generation anti-androgen's going to do. There is a dearth, we had a lot of exciting agents come around with the super castration agents; Abiraterone, Erleada, Enzalutamide, but there's nothing that I would expect over the next year or two that's going to be approved and new.


Joel: What about Darolutamide?


Kenneth: Yeah. In the same class and we'll see.


Joel: Yeah, okay. I think that's going to be in the same class as Erleada in the M0 world. 


Kenneth: Yeah, yeah and Enzalutamide, yeah. 


Joel: Okay, so actually, we're getting ready to close. And before we do, I'm just wondering if you have any additional words or things or thoughts you'd like to share with our audience. 


Kenneth: I think that when I started in this field 30 years ago, the average life expectancy for a guy with castrate resistant prostate cancer was six months. I got into this field because that was really an unacceptable number. 


We now know that the diagnosis of castrate resistance is not an immediate death sentence, so many of those men live more than five years. As we learn how to use these agents in the M0 and low-volume M1 state, we're actually delaying the time to castrate resistance dramatically. 


Men are living much, much longer than they used to and we are now learning how to again, manage their disease in a more chronic state to help guys have good quality of life. I think that it's a time of great hope. I think guys need to know that. 


Diagnosed with metastatic cancer, it means your life has changed and your life is different. But it doesn't mean that this cancer has to take over your life and end it quickly. 


Joel: I really appreciate that positive message. I think it's absolutely true. There are many men who live quite substantially beyond that five years.


Kenneth: Very much so.


Joel: Again, I want to thank you very much for giving us your time and sharing your experience. 


This has been Joel T. Nowak with Dr. Kenneth Pienta, talking about prostate cancer and the development of metastatic disease. Have a healthy and happy day.


[background music plays]