13. Shattering the myth forcing your oncologist to treat you with a dead-end protocol

[00:00:00.250] - Dr. Lemanne

Supraphysiologic huge doses of testosterone actually will treat prostate cancer that is resistant, that has become, that has developed resistance to the androgen deprivation therapy. You have found your way to the Lemanne Gordon podcast, where docs talk shop. Happy eavesdropping. I'm Dr. Dawn Lemanne. I treat cancer patients.

[00:00:32.880] - Dr. Gordon

I'm Dr. Deborah Gordon. I work with aging patients.

[00:00:36.670] - Dr. Lemanne

We've been in practice a long time.

[00:00:39.130] - Dr. Gordon

A very long time.

[00:00:40.730] - Dr. Lemanne

We learn so much talking to each other.

[00:00:42.960] - Dr. Gordon

We do. What if we let people listen? In this episode, Dr. Lemannet and I discuss emerging new ideas in prostate cancer treatment that are about to shift the way oncologists and patients approach not only prostate cancer specifically, but all cancers. The cancer science's primitive is not well known. For example, the definition of cancer. The question what exactly is cancer? Is actually still being debated, and some of the conditions we call cancer may not be at all dangerous. We then dive into one type of cancer, advanced metastatic prostate cancer, which current medical paradigm considers treatable but not curable. The current paradigm of prostate cancer treatment, lowering the testosterone level, was developed back in the early 1940s, and this is still the paradigm in use today, and it has never cured a patient with advanced metastatic prostate cancer. We start by discussing how recent studies show that skillfully administering less prostate cancer treatment can improve not only a man's quality of life, but his length of survival. We go over a study at a major cancer institute that found that patients survived longer when their testosterone lowering treatments were stopped periodically. Using timeframes based on mathematical modeling of each patient's particular psa dynamics, we touch upon the current treatment of advanced metastatic prostate cancer, which involves purposefully but only intermittently, lowering the testosterone level, and how work at Johns Hopkins paradoxically shows that extremely high doses of testosterone can also be used to treat prostate cancer.

[00:02:37.880] - Dr. Gordon

Let's listen. What I brought up to you was a conundrum I'd been discussing with my daughter, who's a registered nurse in a hospital, about the duration of antibiotic treatment. And she was asking me, is it really hard and fast rules that people need to take seven days or ten days or 14 days? And we had a long discussion about it. But where it came down to is, for me, is that we need some research, perhaps. But it would be great to have a little bit of flexibility, according to the patient and their response to treatment, because if you overdo antibiotics, that can be hazardous, too. And if you just keep taking antibiotics because your sore throat now has given you a terrible pain in your right lower quadrant, and a droop. On half your body. Maybe it's just not more antibiotics you need. Maybe it's attention to what's going on. And that is a whole topic in and of itself, which we can talk about sometime, because I know you and I are both really interested in the microbiome, another whole relationship to antibiotics. But what it brought up from your response, which I was so glad because I always want to hear more about, this, is your adaptive and evolutionary principles applied to cancer.

[00:04:08.590] - Dr. Lemanne

You know, Deborah, that makes me think. Your antibiotic example makes me think about evolution. Because of course, one of the problems with overtreatment with the antibiotics is the development of treatment resistance. In other words, the organism that you're targeting with your antibiotic can, over time, if exposed, continuously develop resistance to the treatment. So that the antibiotics, that particular antibiotic doesn't work anymore. And of course, that's a worldwide problem in hospitals. So that's a really important question. And I think that's worthy of a whole discussion and a lot of research. And yes, there's a similar principle in oncology that I really hope people start to think about, especially patients. Doctors are starting to think about this. It's becoming a thing. There's now a cancer evolution working group in the very prestigious American association of Cancer Research, which is one of the largest and best research organizations for cancer in the world. And there are some studies going on in large cancer centers looking at how evolution within a patient. Okay, we're not talking about evolution throughout the various geologic time spans or anything like that. We're talking about how tissues evolve within a single person or patient.

[00:05:39.630] - Dr. Gordon

How my tendon tissue, how my lung tissue might evolve.

[00:05:45.990] - Dr. Lemanne

Yes. So evolution occurs from conception on. And in fact, I think between conception and birth, I think the number is a quarter. I'd have to look this up, but I think we, between conception and birth, accumulate 25%, or a quarter of all the mutations that we're going to accumulate in our entire lifespan between conception and birth. And that's because between conception and birth, what happens. A lot of cell division. Cell division is a very delicate process. And mistakes happen at a stochastic or statistical level. So there are always a certain amount of mistakes in the replication of dna that's involved in the replication and growth of cells and tissues. So there's a certain amount of background damage that just occurs just from that normal process of becoming a fertilized zygote to a baby in the delivery room.

[00:06:49.000] - Dr. Gordon

A full fledged human being. And that does sort of like. There's a side argument about well, wait, if you have a mutation, isn't that the cause of cancer? We talked about a little bit when we interviewed Sam apple, but she said.

[00:07:10.870] - Dr. Lemanne

We think, and this could change, but we think that certain mutations usually are required for progression of cancer. But recent research shows that if you look at skin, for example, okay, there are huge patches of our skin that are completely mutated in the direction of skin cancer. And yet most of us don't develop fatal skin cancers as we age, we may develop small tags that the dermatologist doesn't like and will freeze off, but most of us don't die of skin cancer. But if you look at the skin of someone who's been in the sun in a normal way, who's 25 or 30, there are huge swaths of that skin that look like, that have all the mutations of cancer, including what are called driver mutations, meaning the ones we think drive the growth of cancer. So something is holding those tumorish mutations in check. We don't understand how that works completely, but certainly that's been an area of active investigation.

[00:08:22.610] - Dr. Gordon

And you're talking literally cancer looking like cancer under a microscope, or is there a distinction?

[00:08:29.630] - Dr. Lemanne

I'm talking cancer expression. The genes are damaged in the same way that we find damage in the cancer, in actual cancers.

[00:08:39.770] - Dr. Gordon

And if by, so say, somebody was doing a biopsy and they got some extended area, and the part they were biopsying actually was sort of benign, but they found. Would they actually find something in the other tissue? Is it visible and diagnosable, all these skin cancer mutations?

[00:08:59.930] - Dr. Lemanne

No. So the skin is functioning fairly normally. It's protecting the body. It's not allowing germs and toxins in. It's doing what it should do. So you certainly wouldn't remove it, saying, oh, this is a tumor tissue, and let's just get rid of it because it's mutated. In fact, for most of us, you'd have to remove most of our skin, especially at my age. That's another thing that I really think we doctors don't appreciate enough, and certainly patients don't in most cases. And that's that the definition of cancer is not agreed upon. What is cancer now? It's kind of like pornography in a sense. I know it when I see it. But in terms of everybody agreeing exactly what should be called cancer and what shouldn't be called cancer, that's still being worked on.

[00:09:53.620] - Dr. Gordon

Well, what are parts of that definition? Because I think most of us think we know what it is, but nonverbally.

[00:10:00.690] - Dr. Lemanne

Yeah. So people have made lists of things like the hallmarks of cancer. And those are not just the definition or description of cancer, but the molecular and interactive and physical properties that cancer has. For instance, the ability to metastasize. I think that's what I would call the most important hallmark of cancer, the ability to metastasize and to invade neighboring tissues. So metastasis is the ability to enter the bloodstream that cancer cells have, and to travel to distant parts of the body, away from the area in which they arose, and to set up housekeeping in a new part of the body. So if you have, for instance, a breast cancer, it can invade the bloodstream, can crawl into blood vessels, literally, these cells, they crawl into the blood vessels or the lymphatic vessels, or both, and they take a ride. And when they find a tissue that they like in breast cancer cells, they love bone and liver, right?

[00:11:02.290] - Dr. Gordon

Don't they like liver also?

[00:11:03.670] - Dr. Lemanne

Bone is number one for the most common type of breast cancer, estrogen receptor positive. Breast cancer loves to live in bone because it has a nice environment, it has calcium and certain types of nutrients and things, certain types of signaling that breast cancer cells really like. So bone is a commonplace for breast cancer cells to metastasize to. Interestingly, just a little aside, is that if you've had a broken bone and you get breast cancer, you're liable to get a metastasis in the area of healing of the broken bone, just because there may be some perturbations of the vasculature there, such that cells get more easily stuck in the healed tissue rather than just flowing straight through those kinds of things. We don't know for sure.

[00:11:49.680] - Dr. Gordon

Not just because you're actively rebuilding bone, because, of course, I think I'm trying to get all my older patients to actively rebuild bone. It's not that it could be an.

[00:11:58.330] - Dr. Lemanne

Old fracture decades previously. So, no, it's not necessarily something recent.

[00:12:04.470] - Dr. Gordon

And it has more to do with the architecture of the fracture rather than the process of repairing the fracture.

[00:12:10.820] - Dr. Lemanne

I don't know. I mean, that's a really great question. Certainly wounding causing, especially chronic inflammation that can come with a wound or an area of inflammation that doesn't heal, those do set things up for a cancer in those areas. It's a really interesting field. What is cancer? And the hallmarks of cancer are somewhat helpful, but not the be all and end all. And so what cancer actually is in all cases is not clear. Now, some cases are very, very clear. So an advanced metastatic cancer, say, involving the prostate gland that's spread to the lymph nodes and the bones and maybe the liver and lungs in the end stages, those kinds of things. Sure, that's easy to say. That's a cancer, but early prostate cancer, that's not so clear. And in fact, there's a move to change the name of some of these early precancerous conditions to remove the word cancer from the name. So, for instance, breast cancer, ductal carcinoma inside you. Carcinoma, of course, being the greek word for, or maybe latin, I can't remember. I think it's greek for cancer. Ductal carcinoma inside you. Sounds like cancer. It does. But Dr. Laura Esserman, who's a brilliant surgeon at the University of California, San Francisco breast surgeon, possibly the best one in the world, in my opinion, says that we shouldn't be calling that cancer.

[00:13:44.620] - Dr. Lemanne

And I can't remember the name that she's proposing it be changed to, but it doesn't involve the word cancer. That would be a relief to, I think, a lot of women who have that diagnosis to not call it cancer. But can it progress to cancer? Yes, it certainly can. One of the things that we're trying to figure out is who might that be in whom this condition, which we call ductal carcinoma, incite you, progresses. Those are some things that we're trying to figure out, who will not have it progress. And same situation with. There's a similar situation with prostate cancer. Early prostate cancer is typically described as having a gleason score of six or less. And Gleason scores are scores given to prostate tissue that's been removed on biopsy to describe the number and extent of changes that look like they're moving into the cancer direction. So Gleason seven and higher typically treated as cancer at this point, gleason six and below, not at this point, and usually not treated. And this is just in general. This is not in every single case. But most patients with Gleason six. Prostate cancer are put on what's called active surveillance, used to be called watch and wait, but patients just really didn't like watching and waiting.

[00:15:20.700] - Dr. Lemanne

So now we just changed the term to call it active surveillance. And that's a little more of a happy term for most people. So that's what it's called. But a lot of those patients will not progress. There is some evidence from the work of doctors like Dean Ornish that certain types of dietary interventions may actually decrease the psa, which is the prostate specific antigen, a blood test that measures how much prostate tissue, malignant or benign, that you have in your body. Dr. Ornish's work has found that the PSA can go down in these men with gleason six prostate cancer, or possibly pre prostate cancer. So that's a really interesting finding as well, and goes against this being a true cancer.

[00:16:14.070] - Dr. Gordon

Let's step back a little bit. So my understanding about prostate cancer is that really, if a man lives long enough, does he have 100% chance of getting prostate cancer, or is it, I mean, with a random survey of old men autopsies, what do they find?

[00:16:33.200] - Dr. Lemanne

So I'd have to look up the current state of that investigation. What have recent autopsy studies shown? What are they showing about age and prostate cancer in men? But the last time I looked, I think I would be pretty happy coming away able to say that it looks like most men will eventually have some abnormalities in their prostate with age. That could be called prostate cancer again, depending on the definition. And they may never have had any illness from having these changes in their prostate. And up until the point of death, of course, they. They didn't develop any illness. They died of something else.

[00:17:18.380] - Dr. Gordon

And there. And there's some dynamic relationship between the person and their diet or their immune system or whatever.

[00:17:27.650] - Dr. Lemanne

Oh, absolutely.

[00:17:28.510] - Dr. Gordon

And what would be seen in their blood or prostate. And I'm getting the inference from what you're saying. I'm inferring that it can go either way, that you can have a little bit of pre cancer that can become eventually serious if you live long enough, or you could have a little bit of pre cancer that kind of starts behaving better.

[00:17:49.430] - Dr. Lemanne

Well, certainly Dr. Ornish's work shows that lifestyle matters. He did some interesting work that showed that not only did the PSA stabilize or even go down, depending on how strictly the subjects in his trials attended to the dietary, exercise, stress reduction, et cetera recommendations, but gene expression profiles changed for the better. In other words, their cancers started behaving less. Cancer, like molecularly, lifestyle matters, is it capable of reversing a higher gleason score? Prostate cancer? It doesn't look like it.

[00:18:42.950] - Dr. Gordon

Borderline. So there are some men for whom the prostate cancer gets pretty severe and advanced and life threatening?

[00:18:52.710] - Dr. Lemanne

Yes. And part of that is genetic susceptibility. You may be born with. That's your weak link. Maybe you're not destined to get heart disease. You've got great arteries, not going to get Alzheimer's, got a great brain. But maybe the prostate is a weak link. Genetically, those patients, if they develop prostate cancer, may not be able to do as much with lifestyle as someone who has been dealt a better hand. But still, it doesn't mean that those things are useless. They still have a place and should be maximally utilized, in my opinion, to help whatever other treatments you're doing work better.

[00:19:34.260] - Dr. Gordon

And I know Dean Ornish's protocol. I think it's pretty similar. Whether he's treating prostate cancer or breast cancer or Alzheimer's disease or stress, he has a protocol that is always a, I believe, vegetarian, complex carb diet routine.

[00:19:56.410] - Dr. Lemanne

It's a low fat diet. I don't remember if fish is allowed. I think fish oil pills are. I don't recall the plus or minus with the fish part of things, but it's basically mostly plant based low fat. And there are some other things involved, including certain types of yoga, meditation. Social interaction is a big one with him. If you talk to him, he will tell you that that's a major part of the healing process, in his opinion. So he puts his patients in groups.

[00:20:28.580] - Dr. Gordon

Where they can support each other for whatever condition.

[00:20:32.580] - Dr. Lemanne

For whatever condition. And you're correct. I think he uses pretty similar approaches for heart disease, prostate cancer, and now he's working on dementia.

[00:20:41.350] - Dr. Gordon

Yeah. So share with us, because we've talked about a little bit before, some of the tweaks you make that are more individualized than perhaps standardized when you're dealing with prostate cancer.

[00:20:57.500] - Dr. Lemanne

Are you asking about lifestyle?

[00:20:59.180] - Dr. Gordon

Well, no, not necessarily, because I know that what you've delved into recently really has to do more with the comprehensive treatment and really the chemotherapy of some of the variations in chemotherapy you can apply to some of your advanced patients.

[00:21:19.390] - Dr. Lemanne

Yeah, you're talking, I think, about adaptive therapy, because, you know, I've gotten interested in that recently. Yes, I think it's a really exciting new paradigm for treatment of patients with advanced prostate cancer. Now this is not about patients with new diagnosis of prostate cancer that hasn't spread, is not involving anything but the prostate. That's not what we're talking about here. We're talking about prostate cancer that has metastasized, spread through the bloodstream, the lymphatic vessels, et cetera, to distant parts of the body. And prostate cancer, interestingly, like hormone receptor positive, breast cancer loves to spread first to the bones when it metastasizes.

[00:22:05.730] - Dr. Gordon

Painful, isn't it?

[00:22:06.860] - Dr. Lemanne

It can be very painful and it can be catastrophic. So I had a patient, I think I've told you about this patient, and he gave me permission to talk about his case when he was alive. And his widow has given me permission since to talk about his case. But she brought him into my clinic for a long time now, many years ago now, and kind of dragged him into my clinic and said, do something. He wants to be in hospice. And he was in a wheelchair at that point, and he had prostate cancer that had spread to his spine, and he'd had to have surgery and a rod and things like that. And he had some radiation which temporarily took care of that particular area, and that was expected to heal up somewhat. But prostate cancer that has metastasized is considered incurable. And he didn't want any further treatment, and that was why he had asked to be in hospice. So I talked to him about this, and he said, well, the treatment, which is what's called androgen deprivation therapy, or lowering the testosterone, which is an androgen hormone, a male hormone lowering the testosterone level to starve the prostate cancer cells of their favorite food, creates so many side effects that he just didn't want to do it.

[00:23:30.120] - Dr. Lemanne

So what kind of side effects was he objecting to? So it causes a loss of muscle mass that worsens your ability to get around.

[00:23:42.550] - Dr. Gordon

This is more than somebody walking around who you eyeball and say, I bet they have sarcopenia. This is a kind of muscle mass loss that really weakens the muscles you're talking about.

[00:23:51.400] - Dr. Lemanne

Yeah. It's not too dramatic. There's a really great comparison, a natural comparison, and that's that women have lower muscle mass than men because they don't have testosterone. Now, you can give a person who's phenotypically female testosterone and they will grow huge, big muscles just like people who are phenotypically male, but you have to give that to them exogenously. In the same way, if you remove testosterone from a phenotypically male person, the muscles will shrink somewhat, the strength will go down. I think that's a good way to explain it. Does that make sense?

[00:24:41.920] - Dr. Gordon

Yeah. And so he is somebody who in his life was used to having a certain muscle mass and ability that came with it.

[00:24:48.840] - Dr. Lemanne

He was a competitive athlete. Oh, he was a competitive athlete. He liked to do trail runs and all sorts of things. And he wasn't an elite athlete, but this was important to him. I had belonged to a local gym at that time, and I would always see him there. He was always there and hours a day. And that was a big deal to him. And he would be in these events and compete and get medals and that kind of thing. He would travel a little bit to go to these competitions, sort of like you used to put on competitions. He would go and he enjoyed it. It was a big part of his life.

[00:25:29.860] - Dr. Gordon

Right. Part of his identity, part of his nature, part of, and if he didn't.

[00:25:33.220] - Dr. Lemanne

Couldn'T do that, he didn't really care that much about living. And these drugs cause sexual dysfunction and they cause a change in personality. There's less agency and aggressiveness in a good way. That's a difference for these gentlemen. So he was not happy about this. And at that time, I was just starting to read in the medical literature about some new ways of approaching prostate cancer coming out of the school of evolution. And there was some work at Moffatt Cancer center, which is a large cancer center in Florida, giving mathematically defined dosing intervals of androgen deprivation therapy. In other words, they would give it for a while, get the disease under a certain amount of control using measurements of the PSA, and then they would withdraw the treatment and allow the testosterone level to come up again. And what they were seeing in their pilot trials was compared to historical controls. The patients on that type of a program. Let me put this into context. So we've already talked about the fact that this is always fatal.

[00:26:53.330] - Dr. Gordon

All right, advanced prostate, prostate, not prostate.

[00:26:56.460] - Dr. Lemanne

Cancer itself, but advanced, advanced prostate cancer is always fatal. The treatment, which is castration, basically, and I'll talk a little bit more about that, but nowadays we do what's called medical or chemical castration. We give pills to turn off testosterone production, causes the side effects we've just talked about. But it also pretty immediately causes a dramatic regression of the prostate cancer. Even if it's metastatic, all the lesions in the bones go away, the scans get better, the psa goes down. So in spite the side effects, these patients look better. The problem is, if you give these drugs constantly, after one to two years, every single patient has disease that becomes resistant to these drugs and the disease comes back worse than ever, grows fast, and the patient dies.

[00:27:47.440] - Dr. Gordon

So they are without their testosterone for a couple of years, feeling gradually weaker and weaker, probably, or not accommodating, and then the cancer comes back with a vengeance because it works its way around the strategy.

[00:28:01.830] - Dr. Lemanne

Perfect. I love that description. Yes, works its way around. So if we are able to pulse the treatment, it turns out that the pilot studies at Moffatt cancer center showed that these gentlemen did much better. The historical controls all progressed after about a year, I think it was 13 months, every single one. And most of the patients in the experimental group did not progress. And I think one did. I want to say there were twelve or 15 in this small pilot. And out of that number, one did progress, but the others did not over a year. And what was really interesting was that these patients overall got about 40% the amount of treatment that the historical controls. Well.

[00:29:02.900] - Dr. Gordon

So out of a year, they might have just been on their treatment, their testosterone suppression, for less than half the year.

[00:29:10.720] - Dr. Lemanne

Yes, exactly. So they had fewer side effects. They did have some, of course, when they were on it, but they had fewer side effects and the treatment worked better. And what was really interesting is that each patient needed a different schedule. And the schedule was calculated based on the speed of the rise and fall of the prostate cancer growth, which was estimated by the speed of the rise and fall of the psa, which is a simple blood test. Prostate cancer is an easy disease to use this method on because it has such a great, easy to obtain marker, a blood test that tells you whether the tumor is getting worse or better at that particular moment. So this was a perfect tumor to start these kinds of trials in.

[00:29:58.180] - Dr. Gordon

And from the doctor's point of view, yes, that's great. But from the patient's point of view, I think there's a couple of interesting things here. I would imagine that ovaries give up the ghost at some point. They do that in menopause. And even when you hammer away at the testicles with androgen deprivation therapy for a long time, the testicles come back and start making more testosterone again.

[00:30:25.800] - Dr. Lemanne

They do. Now, it's not perfect, and it can take a long time. It takes several months sometimes for men to get back to their pretreatment blood testosterone level. But yes, having some treatment is reversible. Is reversible to a certain extent, and.

[00:30:46.430] - Dr. Gordon

Probably having some is better than none. I mean, there's plenty of men walking around with pretty low testosterones who kind of have to be really show them the blood work and say, no, you're at the bottom end of a big curve. So a little bit is probably better than none.

[00:31:02.950] - Dr. Lemanne

You want to know something really wild? Yeah, a little bit is better than none, but keeps the prostate cancer cells growing. A lot of testosterone, supra physiologic testosterone. This is really fascinating, supraphysiologic. Huge doses of testosterone actually will treat prostate, prostate cancer that is resistant, that has become, that has developed resistance to the androgen deprivation therapy.

[00:31:35.220] - Dr. Gordon

Oh, my goodness. So Arnold Schwarzenegger is not going to get prostate cancer.

[00:31:40.070] - Dr. Lemanne

No, actually, the kinds of anabolic steroids that bodybuilders use are not built for this. So they're a little bit different. So, no, that won't work. Okay. All right. Testosterone, I think it's cypionate, which is an injection you give 400 milligrams once a month. That spikes the testosterone to several thousand, where the normal is up to 800 or 1100 or so in young men and about three or 400 in older men. But it spikes the testosterone up in every man who gets this injection for a few days, and it kills off the prostate cancer cells that have become resistant to low testosterone treatment. So I'm not going to go into all of the biology of this, but this is something that my patients have been looking into and that a couple of them have been trying, and I think it's really exciting. This is work that's being research work that's, this is out of research work that has been done at Johns Hopkins. So it's not a fly by night or particularly alternative or anything like that, but it certainly is a different paradigm and a different way of thinking about prostate cancer.

[00:32:55.770] - Dr. Gordon

Absolutely. And how do the men experience that? Supra physiological dose.

[00:33:00.930] - Dr. Lemanne

They like it so they are able to put back on muscle, they have sexual functioning return and their lipids normalize because of the metabolic problems that you see with androgen deprivation therapy. Those can be serious. Most men with prostate cancer actually die of heart disease, or a large proportion of them. So things get better during the moment that they are on high doses of testosterone. We then withdraw that. And what's interesting is they're still using the androgen deprivation therapy, so we don't let them make their own testosterone via their testes.

[00:33:37.630] - Dr. Gordon

At this point, you select the form of testosterone they're going to have.

[00:33:42.020] - Dr. Lemanne

Yes. So I think this is a really exciting new way of approaching cancer. We can apply this. I've tried this with patients who have other diseases like breast cancer. As long as there's a blood borne marker that we can measure, we can estimate the disease burden easily with. We can do this with any cancer. We can try pulsing the treatment using mathematical modeling. One of the things that, and again, I've tried that with a couple of other patients, including a breast cancer patient. But one of the things that patients have to understand is that we're not trying to cure their cancer with this. And when we withdraw the treatment, the cancer blood marker is going to go up. That is spooky for most patients.

[00:34:33.920] - Dr. Gordon

Oh, just bear with it.

[00:34:35.670] - Dr. Lemanne

Just bear with the cancer. Grow back. But we found that if you maximally suppress, for instance, in prostate cancer, the PSA, try to drive it down as low as you can, you make the situation worse. You really want to maintain some level of disease, usually about 25% of 25% to 50% of the starting PSA level. You want to maintain that. You don't want to press the PSA down below that if you can, because you want to maintain a population of treatment sensitive cells. If you wipe them all out, what are you left with? You're left with the cells that are completely resistant.

[00:35:14.570] - Dr. Gordon

Oh, and then they become the dominant population.

[00:35:19.910] - Dr. Lemanne

And you know what's really interesting is if you have a population of tumor cells and some are sensitive and some are resistant and you're not treating them, the resistant cells will always be in the minority, because in the absence of treatment, the sensitive cells are much stronger. So they get the resources first, they're more aggressive, they get first pass at waste removal, oxygen levels, blood flow, all of that. And why is that? It's because if you have decided that you're going to be a treatment resistant cancer cell, you have to build and maintain a treatment resistance apparatus. And these are literally things, okay? These are enzymes and pathways within the cancer cell that have to be maintained that will do things like detoxify a chemotherapy or antiaging.

[00:36:16.480] - Dr. Gordon

Disable it?

[00:36:17.420] - Dr. Lemanne

Yes, or will pump it out of the cell. You have to have some kind of pump. Those take energy, atp, that's atp, or the energy coin of the realm in biology that you can't use to grow and divide and make progeny. So if there is no treatment around, the treatment resistance apparatus is a burden. So those, it's a lot of work that maintain it, are always at a disadvantage when in a population mixed in with a population of treatment sensitive cells that haven't bothered to prepare for the future. And one of my colleagues, Robert Gatenby, who's just a phenomenal thinker in this realm and researcher, describes it as being carrying around an umbrella when it's not raining and then trying to run a race with, know, with a whole bunch of umbrellas. Of course the guys without umbrellas are going to beat you if there's no rain. Once the rain comes, the chemotherapy or the androgen deprivation therapy, boy, the ones with the umbrellas are going to be.

[00:37:23.570] - Dr. Gordon

Doing well, but you don't want to eradicate the other ones who would otherwise crowd out the umbrella carrier.

[00:37:31.510] - Dr. Lemanne

Exactly. That's a great way of describing it.

[00:37:35.010] - Dr. Gordon

I think the temptation when you hear the word mathematical modeling is to imagine that it mathematically models that for prostate cancer, you do it every 17 and a half weeks, something like that. But it's really mathematical modeling based on careful following of that individual's values.

[00:37:56.450] - Dr. Lemanne

That's correct. So yes, one man might need a treatment pulse every 17 and a half weeks. And another one needs one every two and a half weeks. In the pilot trial, it did look like that there was one patient who had to have a pulse of treatment about once a month, and there was, I think, one that needed only one or two a year.

[00:38:20.530] - Dr. Gordon

Wow.

[00:38:21.340] - Dr. Lemanne

And everybody else was kind of in between that. So, yes, there's a large range, and it's very individual, and it can change. So tumors have their seasons, they have dormant seasons, which we don't understand completely. So that can change within a patient. So it's important to keep measuring and modeling and adjusting the treatment intervals based on the results of those models produce.

[00:38:49.330] - Dr. Gordon

Two questions swimming around in my head. One of them is the relationship between prostate cancer and estrogen, because I imagine that it's high testosterone in the setting of high estrogen, that is more problematic for the prostate. Is that a misapprehension?

[00:39:08.130] - Dr. Lemanne

So that's a really good question. So I have a couple of patients who are actually using estrogen as treatment for their prostate cancer with good effect. And the dose is estradiol, eight milligrams a day.

[00:39:21.730] - Dr. Gordon

That's a lot.

[00:39:22.740] - Dr. Lemanne

It is, but I think it shuts down the pituitary production of all hormones. You're turning off lh, fsH, and all of that. So the testes are shut down. So that may be at least part of the mechanism. We don't understand that completely as well, but that is something that we see. I want to just let people know that even something as common as prostate cancer, for which we have a lot of treatments, remain mostly a mystery to us. There was a doctor named Charles Huggins, and I think he got the Nobel Prize. He wrote a paper in 1941 about surgical removal of the testicles as treatment for advanced metastatic prostate cancer, which is.

[00:40:13.080] - Dr. Gordon

Kind of what they're doing temporarily with the blockade.

[00:40:15.640] - Dr. Lemanne

Yeah, so. Exactly. So that's castration. Technical term for that operation is orchiectomy. But men who underwent that operation got better for a while. Their bone pain went away. They got up and out of their wheelchairs and walked around again, and it was pretty spectacular. But they always relapsed. In other words, the disease always came back.

[00:40:43.150] - Dr. Gordon

The patients died, always came back.

[00:40:44.980] - Dr. Lemanne

Always. Oh, always. This is not a curable situation. But this was 1941. Dr. Huggins did incredible work. He got the Nobel Prize, I believe, to look that up, but I think he did. And the thing is, this is, what, 1920, or this is 2024, almost 100 years later. This is still our treatment for prostate cancer, right?

[00:41:08.790] - Dr. Gordon

We do it a little, and it.

[00:41:10.010] - Dr. Lemanne

Still doesn't cure anyone.

[00:41:11.130] - Dr. Gordon

Still doesn't cure chemical castration or medical castration.

[00:41:15.590] - Dr. Lemanne

We give pills, injections, things like that, to turn off the testicles or block the uptake or use of testosterone by cells individually. But this is the treatment. Yes.

[00:41:29.180] - Dr. Gordon

Wow. My other question was your gentleman patient, the athletic hyper performer in the wheelchair?

[00:41:37.030] - Dr. Lemanne

He got out of his wheelchair, he started running races again.

[00:41:40.450] - Dr. Gordon

Running races?

[00:41:41.510] - Dr. Lemanne

Yes. He showed me his little medal. He ran in some trail run. Yeah, it was not little. I think it was like 20 miles or something.

[00:41:54.220] - Dr. Gordon

Definitely not little.

[00:41:55.580] - Dr. Lemanne

It wasn't just the Halloween children's costume run or something. This is like a real race. And yes, he was happy. So that was a good icon. He eventually did die of prostate cancer. We have not perfected at that point at least. We weren't very good at this particular approach. But he got a couple of good years out of his years wheelchair and doing. He traveled, he ran in his races. He was at the gym all day, I can attest to that. And he was doing what he wanted to do. He had a good couple of years and he was not in hospice.

[00:42:39.890] - Dr. Gordon

Well, I bet he was glad he got wheeled into your office.

[00:42:43.520] - Dr. Lemanne

But this approach has progressed since then. We know more now. That was about seven years ago, I think. Add it up. But yes, we're learning more and we're better at it. It still needs some work, but I think it's superior to, or probably going to be proved superior to the current level of treatment, which is just not very good.

[00:43:04.490] - Dr. Gordon

And how pervasive is this awareness of a possibility of pulsing the treatment depending on the patient's response?

[00:43:12.180] - Dr. Lemanne

Well, you know, this is something that patients are more aware of, I think, than many doctors, including oncologists, because patients now are forming patient advocacy groups and patient research groups. So the bipolar androgen therapy, I think, was promoted by a patient, I think, somewhere in Ohio, who worked to get hopkins and other places to actually start these trials and look into this kind of approach.

[00:43:48.090] - Dr. Gordon

You just said bipolar androgen therapy. Sorry.

[00:43:50.810] - Dr. Lemanne

Yes. So bipolar androgen therapy is the high dose testosterone therapy used after development of resistance to androgen deprivation therapy, injections of.

[00:44:06.610] - Dr. Gordon

High doses of testosterone cyprianate.

[00:44:08.740] - Dr. Lemanne

Yes.

[00:44:11.330] - Dr. Gordon

So the initial protocol where the treatment is pulsed, that's something you think that more patients are aware of, but it's gaining some acceptance among.

[00:44:21.790] - Dr. Lemanne

Yes, I think patients are aware of and are driving oncologists to become aware of these new approaches because the old approaches just aren't satisfactory.

[00:44:33.010] - Dr. Gordon

It reminds me of something you said some time ago, because you and I are both rather meat eating people and keto more than high carb. And there is a celebration of the keto diet for cancer treatment in social media in general. And you said cancer is smarter than know that you have to vary the diet. And sometimes it might be even vegan, and sometimes it might be keto.

[00:45:03.990] - Dr. Lemanne

So it appears that it depends on the stage of the prostate cancer. So Dr. Gatenby, whom I mentioned before, who's at Moffat Cancer center, has done some work in rodents, and he used a strain of rodent, I believe they're rats, but I'm not sure that always develop prostate cancer. They always develop it at one year and die of it shortly thereafter. Their life expectancy, I think, is two years, something like that. Anyway, he found that if you give these mice, who are always going to get prostate cancer, alkaline water, and it wasn't fancy alkaline water like we can find here in Ashland for $8 a bottle. This was arm and hammer mixed into their drinking water. Okay, so if you made them drink that, they never developed invasive prostate cancer.

[00:45:52.820] - Dr. Gordon

Interesting.

[00:45:53.470] - Dr. Lemanne

Ever. Okay. As long as you gave it to them when they were young. If you started this when they were mature, it didn't work. So it had to be instituted when they were young, but it prevented incite you prostate cancer into invasive or the deadly kind of prostate cancer. Again, this did not work, though, if it was instituted after maturity. So if the mice were adults and they started this, they still got their prostate cancer. It was invasive and they died of it. But it's really interesting, and there's some other work that makes it look like early prostate cancer may be controlled by a low fat, probably low calorie ish diet. Whereas once it becomes metastatic, the tumors that have metastasized to the bone are very, very interested in glucose and glutamine and exhibit the varburg, the Warburg effect. And in those patients, you may be better off using a ketogenic diet. Now, it can be that the patient has both types of cancer in their body. What do you do then? Yeah, I think that's a good question. We may have to cycle the diet, something like that. But the take home from this, I think this idea is that one diet does not fit all.

[00:47:10.920] - Dr. Lemanne

And there is no one anticancer diet, as best we can tell. It depends on who you ask. But in the case of the early prostate cancer, it looks like perhaps low fat might be important.

[00:47:27.470] - Dr. Gordon

Interesting. And even when it comes to something as uniformly accepted as hormone deprivation therapy, the patient's response, there's not only a variation in the time of cancer, there's a variation in that whole individual's milieu, certainly in Alzheimer's research. Dr. Bredesen has said if he had a nickel for every time a rat was cured of Alzheimer's disease, he'd be a very rich man. The rodent study that you talk about in prostate cancer, they are a uniform species living in a uniform environment. And it makes sense that humans, who are so much more complex, living in the real world, with all their proclivities and habits and background, are going to need to be paced and evidently fed differently.

[00:48:23.890] - Dr. Lemanne

Yes. Than rodents.

[00:48:27.010] - Dr. Gordon

Than each other, I mean, than each other.

[00:48:30.950] - Dr. Lemanne

Got it. Well, you know, I was thinking. Yes, of course, you're right. I was thinking, though, Dr. Gatenby taught me something recently. He said, well, rodents are really small, and so their tumors are small. The blood vessels and capillaries, though, are about the same size as ours. But because of the difference in size, the physiology, the physics of all of the flows and fluids and things like that, the dynamics are very, very different in a larger, interesting animal like a human being, one that's just physically larger.

[00:49:03.610] - Dr. Gordon

So now we're doing math and physics.

[00:49:05.960] - Dr. Lemanne

Yes.

[00:49:06.340] - Dr. Gordon

In this cancer treatment.

[00:49:07.250] - Dr. Lemanne

Well, you know, cancer, the cancer research really took a big leap forward when about 20 years ago, the NIH said, you biologists are just not getting very far with cancer. You've been trying for 100 years and nothing's happened. We're going to get physics physicists to come in and take a look at the field of cancer and see what they come up with. And what the physicists came up with was this idea of evolution really an organism and within a cancer that even.

[00:49:38.970] - Dr. Gordon

Sounds kind of biological for physicists to think about. But their observational prowess must have led.

[00:49:47.630] - Dr. Lemanne

Them to that observation. New eyes. Yeah, not an old problem. And biologists were looking at this molecular pathway and that molecular pathway and this chemical reaction and all that. And the physicists started asking some other questions like, well, how stiff is the tissue and how permeable is it? So things like that matter. So, for instance, in brain cancer, older people have less stiff brains, and so cancers in the brain can spread more easily because of that lack of stiffness. And we've noticed for a long time that patients with brain cancers who are older do much worse than patients who are younger. Right.

[00:50:26.230] - Dr. Gordon

I think some young children can do really well with it.

[00:50:30.190] - Dr. Lemanne

Right. Well, better than older adults if they have the same kind of. So, glioblastoma, for instance, same tumor in an old patient versus a young patient. There's a difference in survival.

[00:50:40.820] - Dr. Gordon

Time of survival, physics, math. Pretty soon there'll be foreign languages in.

[00:50:46.820] - Dr. Lemanne

I think they've always had that carcinoma. I couldn't remember whether it was Greek or Latin. I think cancer is Latin, right. Means crab in Latin. Is that crab? Yeah, I think.

[00:50:57.570] - Dr. Gordon

Well, we'll have to get.

[00:50:59.040] - Dr. Lemanne

You're the one who took Latin, right?

[00:51:00.610] - Dr. Gordon

I did take Latin, but I remember the word for farmer, but not for farmer. A Greek. Allah.

[00:51:09.270] - Dr. Lemanne

Okay. I think the greek word is Georg, from which our word George comes from our name.

[00:51:15.050] - Dr. Gordon

George means farmer, I think.

[00:51:16.650] - Dr. Lemanne

So. Geo urge. World move, earth mover. Yeah, something like that. I'm not a good language person, but I think it's interesting.

[00:51:26.030] - Dr. Gordon

Well, this is fascinating. There's this whole body of cancers which you've described as being accurately. So is this treatment really works? We've got this one down. If it's early enough and it falls in these categories, we know how to treat this cancer, but all these other ones, and particularly what we're talking about today, advanced prostate cancer, not treatable. This is okay, we're not getting you down to zero cancer, but we're getting you back to living.

[00:51:58.150] - Dr. Lemanne

Yes. Not treatable. I would say it's not curable.

[00:52:03.630] - Dr. Gordon

Not curable.

[00:52:04.690] - Dr. Lemanne

There's kind of a buzzword in oncology, and I was taught to say this to my patients when I was a fellow. An oncology doctor in training is a fellow. You tell patients your cancer is not curable, but it's treatable. And that it bothers me a little bit, because I think what it puts into patients minds is that, yes, okay, we're going to turn it into a chronic disease like high blood pressure or diabetes, and then they think of their friends and relatives who live with those conditions for years and take a pill and nothing happens. That's just not a cancer. We see, with trying to turn cancer into chronic disease, we see patients who have to have, most of the time, a lot of treatment, very little time off treatment, or on quiet treatment periods, and with lots of side effects and then eventually death. So I don't like that term. Cancer is not curable, but treatable anyway. I just am not a fan of it.

[00:53:06.240] - Dr. Gordon

It's a whole different thing, having what you perceive of as a normal life and having to go in for blood tests every once in a while, compared to a diabetic who might have to adjust everything in their life around their diabetes if they never really get a handle on it. So that your gentleman who got out of his wheelchair. It was essentially a cure in the moments he wasn't going back in for a little bit more treatment.

[00:53:29.560] - Dr. Lemanne

Well, while he was out running his trail runs and everything, just what he wanted to do.

[00:53:32.940] - Dr. Gordon

Well, this is great. And it helps me understand how you can say math and highly individualized in the same sentences as cancer management.

[00:53:44.470] - Dr. Lemanne

Yeah, each patient gets their own model.

[00:53:48.250] - Dr. Gordon

That's great.

[00:53:51.290] - Dr. Lemanne

It's kind of a cool thought, having your own mathematical formula, having your name or a Social Security number. You can have your own formula, your.

[00:53:57.890] - Dr. Gordon

Own math formula for highest quality and longest life of survival in a dire situation. Yeah, sounds great. I'll sign up for it.

[00:54:09.710] - Dr. Lemanne

Great to talk to you, Deborah.

[00:54:10.860] - Dr. Gordon

Great to talk to you. See you next time.

[00:54:13.000] - Dr. Lemanne

Bye bye bye.

[00:54:16.130] - Dr. Gordon

You have been listening to the Le Mon Gordon podcast where docs talk shop.

[00:54:21.920] - Dr. Lemanne

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[00:54:58.180] - Dr. Gordon

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[00:55:10.210] - Dr. Lemanne

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[00:55:24.830] - Dr. Gordon

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[00:55:31.600] - Dr. Lemanne

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[00:55:49.890] - Dr. Gordon

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