Interview with Dr. Peter Attia: Detect cancer early and before it spreads
In this latest video from MedCram, Kyle Allred interviews Dr. Peter Attia on what his recommendations are for detecting cancer early and before it spreads. Below is a transcript of the video with Kyle and Dr. Attia.
– I am excited to be here with Dr. Peter Attia, who is perhaps the leading expert on communicating what things we’re most likely to die from, how can we prevent them, and how can we use data-driven approaches to optimize our health now and for as many years as possible. Dr. Attia’s medical degree is from Stanford, he trained at Johns Hopkins General Surgery, and he also trained as a surgical oncology fellow at the National Cancer Institute. He’s the founder of a website called Early Medical, the host of a popular podcast called “The Drive,” and the author of “Outlive,” a fantastic book just published. We’ll discuss several topics from it. Dr. Attia, welcome.
– Yeah, thank you so much for having me.
– Well, we’ll get to strategies and specific tools for optimizing our health and avoiding cancer and disease in a minute. But, first, for someone watching this, what are they most likely to die from, and why is that so important to know?
– Well, given that we’re watching this in 2023 and not, you know, 1823, it looks a lot different than it did historically, at least for most of our evolutionary past. Today, we’re most likely to die from things that I call slow deaths. Whereas for virtually all of our existence, we were more likely to die from fast deaths. Fast deaths are things like infections and trauma. But today, we’re gonna die from chronic disease, most likely. And those chronic diseases in rank order approximate cardiovascular and cerebrovascular disease, cancer, and neurodegenerative disease. We also have a whole host of metabolic diseases that, while they don’t directly result in loss of life at as high a frequency, contribute overwhelmingly to the suite of chronic diseases I mentioned above. So, things like type 2 diabetes, non-alcoholic fatty liver disease, insulin resistance, they don’t show up directly on death certificates that often, but their contribution to those other three is enormous. So collectively, I call those the Four Horsemen of Death.
– And in your book, you talk a lot about the difference between lifespan and healthspan. Can you review what that difference is?
– Sure. Lifespan is, I guess, the easier of the two to understand because it’s quite binary. You know, you’re either alive or you’re dead, and you’re breathing or you’re not. And so, lifespan is essentially the length of your life. And a part of longevity is asking the question, can we extend that period of time? But an often overlooked component of longevity is healthspan, and healthspan is quality of life. And that’s much harder to define because its medical definition is relatively useless. The medical definition of healthspan is the period of time for which we are free from disability and disease. But, you know, I think most people would agree that even as you age, even if you do so without disability or disease, your physical and cognitive performance, for example, deteriorate. Also, your emotional health, which doesn’t really fit into a disability and disease standpoint, unless, of course, we’re talking about it rising to the level of true mental health, will clearly contribute to your quality of life as well. So, quality of life, at least around these three areas of physical, cognitive, and emotional health contribute at least as much and probably more to the overall concept of longevity.
– Another concept that you mention a lot in your book is this difference between medicine 2.0, as you call it, kind of the status quo, what we have right now, versus medicine 3.0, something that you talk about with your patients and practice yourself. Could you give us kind of an overview of the difference between these two?
– Sure. Medicine 2.0 is the system of medicine that we evolved to, obviously, for medicine 1.0, in the latter part or middle part of the 17th century, with the kind of elucidation of the scientific method, all the way into the latter part of the 19th century with the development of the light microscope, and ultimately, into the early 20th century with the development of antibiotics, antimicrobial agents, and, of course, vaccines. And what medicine 2.0 then did was allow us to basically dramatically cull fast death. So we took fast death, which, again, for all of our existence, for, you know, millions of years, was effectively what was going to end our lives. And that meant we were gonna die somewhere in our 30s to 40s, typically, if we managed to survive childhood and infant mortality was through the roof. So mothers are basically dying at an alarming rate every time they’re giving birth to a child. It basically allowed us to escape that and get to the point where we are now primarily dying of these chronic diseases that we talked about a minute ago. So medicine 2.0, says, “Look, we’re gonna still use the same playbook “to go after those diseases.” Different set of diseases. You know, we’ve hit it out of the park with infectious diseases, communicable diseases, and trauma, so now let’s ask the question, what if we take the same playbook and apply it to chronic diseases? The playbook being you come up with a diagnosis, you treat pharmacologically, surgically, or however, once that disease is present. And I don’t need to state the obvious here, but that approach has been largely unsuccessful against chronic diseases. Chronic diseases are not as amenable to that strategy. And when you apply the tactics and strategy from med 2.0 to the current suite of problems we have, we have not been very successful. And it’s so stark that if you take a look at the life expectancy of people 120 years ago and you strip out the top eight infectious and communicable diseases, you realize it’s almost the same as it is today. So, yes, it’s true, we have doubled life expectancy, but that has come almost exclusively through the lens of those early successes of medicine 2.0. So the question then is, what is medicine 3.0, and why would it be different? And it basically comes down to a fundamental philosophical shift around the acceptance of prevention and very, very early prevention.
– Many people watching this are gonna be watching from the United States, and they’re familiar with this medicine 2.0 paradigm, where, like you said, we wait till a disease happens, and then we try to treat it. Are there any countries or places that have this better than we do and are more on the path towards medicine 3.0 that you’re aware of?
– Yes, although, only sort of slightly, right? So there are definitely countries in Europe that have a bit more of a preventive strategy. It’s largely a result of their healthcare systems. So the US healthcare system is not really well geared up for medicine 3.0. In fact, the transition to medicine 3.0 will be harder in the US than in many other countries, and one of the reasons for that is just a structural reason that has to do with the financial incentives and remuneration for how healthcare is compensated. So in a system like ours where the majority of care, especially early in life, is private, not public, not single-payer, the financial incentive is really geared towards getting paid to treat disease. Now, I’m not advocating for a single-payer system because I could argue with equal veracity why a single-payer system is usually quite unsuccessful as well. So it really probably needs to be a hybrid. But here is where the single-payer system does get a nod. Which is, it is easier to tweak the incentives towards prevention because you don’t have the financial incentive to provide delayed treatment. In other words, in a single-payer system, the payer, which is the government, owns the risk of disease for the duration of your life. Conversely, in a system like ours, healthcare is very portable. So who’s your insurance carrier right now?
– Moda, which is just a local one in here in Oregon.
– Okay. So, you know, can’t speak to them specifically, but let’s just assume, you know, they might only own a life, meaning own the risk of that person’s life, for, you know, five or six years. So are they really interested in putting the time, effort, and resources into prevention when you’re in your 20s and 30s if those things are only going to reap rewards when you’re in your 50s, 60s, 70s, or 80s? It’s very unlikely. Again, this is one of many of the structural challenges with transitioning from medicine 2.0 to 3.0. But to your question, countries that have a single-payer system have a much easier time making that transition because, if you’re in Canada or the UK or Australia, or many of the European countries, the government is effectively backstopping your healthcare.
– Well, I wanna get into one of the Horsemen that you mentioned, cancer. And this is a topic of particular interest to me because I was diagnosed with a type of cancer called Hodgkin lymphoma about six months ago. Fortunately, it has a very high survival rate and a complete remission rate in someone my age, so it’s likely that the chemotherapy that I’ll be finishing up soon will be the only treatment I need for this. But my personal interest in screening for cancers is higher than it was before because I’ve been reminded firsthand that cancer, you know, can and does happen in 40-year-olds like me without other medical problems or a strong family history of cancer. So let’s hear about your approach to cancer, again, within this kind of medicine 2.0, what we have now and what you would like to see, and what you recommend with your patients regarding cancer.
– Well, each of the Horsemen has a slightly different playbook to go down the medicine 3.0 route. And truthfully, when it comes to cardiovascular disease, it’s the easiest of the lot because we have both the greatest understanding of what causes it and the greatest set of tools to prevent it. So, in other words, if we really know what’s driving it, you know, we could go down that rabbit hole in detail, and we happen to have all the tools in the world, pharmacologically and non-pharmacological, to lay down the prevention gauntlet decades in advance. With, let’s take Alzheimer’s disease, we actually have quite a strong sense of what the drivers are. Some of them are not modifiable, they’re genetic, but many of them are highly modifiable. And we have some sense of what tools to use, therefore, to prevent it. Unfortunately, we have very few tools to treat it once it’s present. So cancer occupies kind of a unique place in that landscape, in that we frankly have, hands down, the least understanding of what is driving it. We know a few things, right? We know that smoking dramatically increases the risk of cancer, but I’m willing to guess you were not a smoker.
– We know that the second leading environmental or modifiable risk factor for cancer is obesity. Which really isn’t about obesity. It’s probably much more about the internal environment that tracks with obesity, namely hyperinsulinemia and inflammation. And again, I’m guessing that that was not necessarily risk factors for you as well. So what that leaves us with is, at the end of the day, cancer is very much about bad luck. In other words, cancer is a condition, where the majority, meaning 95%, arise from what are called somatic mutations. So these are not mutations in genes that you acquired from your parents. These are genes that you inherited that were completely normal, but over the course of your life, and again in your life being so short to date, that you’ve already had this bad luck of acquiring enough mutations to drive a cancer. And the reality of it is, if we were sitting here five years ago having this discussion before you had cancer, I could have told you everything under the sun to do to minimize that risk, and maybe it would have, but ultimately, you could have still come down with cancer. So why am I saying all of this? Well, I’m saying all of this because what it does is it calls to our attention another tool that is essential in our fight, if you will, against cancer, and that is the tool of very early and aggressive cancer screening. Now, that’s a highly controversial topic. I’m happy to talk about all the controversies. But the rationale is unambiguously straightforward, based on the following. There is no example that I am aware of, of a cancer where the odds of eliminating it go down as the tumor burden goes up. Meaning the fewer cancer cells a person has in their body, the more effective the treatment. And I think the simplest explanation for this is that the more cancer cells you have, the more heterogeneous the population of cancer cells, and the more heterogeneous the mutation burden. And as that burden of mutation rises, you have greater and greater chances for escape. Meaning you provide a systemic treatment like chemotherapy, and you have a greater and greater likelihood that some cancer cells will actually be able to evade the therapy and go on to develop a new population of cancer cells that will be resistant to treatment. And so, the easiest way to look at this is just to look at colon cancer or breast cancer, for which we have so much data. And I write about both of these in the book. Where if you take a patient with stage-three colon cancer, for whom you resect the colon and you resect the lymph nodes around, but there is no gross or visible spread of the disease, say, to the liver or other organs, and you give that patient a chemotherapy regimen, their survival in five years is very high. You know, 60%, 70%. If you take a group of patients with metastatic colon cancer, so the exact same patient, but now the cancer is also in the liver, so you can actually see it, and you give them the exact same chemotherapy, none of them will be alive in five years. Again, similar examples with breast cancer and other forms of cancer. So regardless of how much we do individually to reduce our risk of cancer, and we can talk about all of those things, the importance of exercise, nutrition, sleep, probably, and clearly mitigating factors like insulin resistance and smoking, at the end of the day, we are still, every one of us, susceptible. And therefore, I think it’s imperative that we at least consider what very early screening does to give us a chance to, if we do have cancer, fight it with the smallest burden possible.
– And another thing that you mentioned in your book that convinced me on the importance of early and aggressive screening, is you point out that treatments over the last 50 years for cancer haven’t really come along that far. There’s been certain kind of exceptional cases, lymphoma, leukemia, for example, but for the most part, are overall survival rate from cancers is not much better than it was several decades ago. Is that right?
– For metastatic solid organ cancers, so that does not include leukemias and lymphomas, especially Hodgkin’s lymphoma, where the field has had remarkable success. When you talk about epithelial tumors, solid organ tumors, it’s been an improvement in overall survival of 5% in 50 years.
– Now, we’re starting to see those numbers get better and better with immunotherapy, and specifically, a type of immunotherapy called checkpoint inhibitors. So I think we’re probably getting to the point now where maybe that number’s getting closer to a 10% improvement over where we were, because approximately 8% of all tumors today are now responsive to immunotherapy. And immunotherapy has the advantage of when it works, it is usually a very durable remission, meaning that remission tends to stay, it is effectively a cure. So of all the things that I think have come along in the past 20 years, I think immunotherapy is, by far, the most interesting part of cancer treatment. I was very fortunate in that just by luck, that’s what I did my research in. So back as a medical student, you know, when I went over to the NCI, the National Cancer Institute, I spent time working there. And then, I went back again for a fellowship more formally when I was in residency, and had the great pleasure of spending two years working in the lab and doing that type of work. At the time, it was pretty much exclusively a treatment for melanoma and a little bit of a kidney cancer called renal cell carcinoma. But we were just starting to see the power of checkpoint inhibitors, which we used, at the time, in melanoma. And today, we realized that these checkpoint inhibitors can work on any tumor, provided they have a certain type of mutation. Now, the goal is, what does it take to create and unleash the immune system on any type of cancer? How do you do this when we know, by the way, that 80% of solid organ cancers have cancer antigens that are recognized by the immune system?
– I wanna talk about each specific type of cancer screening that we have available that you recommend. And I think it’s helpful the way that you organize kind of the two big buckets of cancer screening into cancers that happen inside the body and cancers that happen outside the body. Can you kind of go over that distinction?
– Yeah, it is kind of funny because most people don’t think of their colon or their stomach as outside their body. And I understand why, of course, but you have to think about it through the lens of embryology, right? You sort of develop in these multiple layers, three layers to be specific. But the easiest way to think about it is, can the air that you breathe or that’s outside your body, can it get to the tumor? Can it touch the tumor directly? So, for example, when you consider all of the skin cancers, the answer is yes, right? Everything on the outside of your body, vis-a-vis your skin, is exposed to the outside world. But what’s a little more less intuitive is that everything from your mouth to your anus is also technically outside your body. Now, the significance of this is primarily that you can look directly at it, right? It’s that you can take a direct look at these cancers. And where it gets particularly noteworthy, at least in the United States, is that colon cancer is the third leading cause of cancer death. So you have the number one being lung cancer. Number two is kind of split between genders. So if you’re a man, it’s prostate cancer. If you’re a woman, it’s breast cancer. And then number three, straight across the board, is colon cancer. And interestingly, colon cancer, unlike the others that I mentioned, lung… Which, by the way, lung doesn’t occur in the air sac. So what I said about being able to look at it directly doesn’t really apply to lung. But what’s amazing is that you can look directly at the colon as it transitions from being perfectly normal to developing something called a polyp. And that transition is a necessary first step towards the development of colon cancer. Now, most polyps do not become colon cancer, but every colon cancer comes from a polyp. And this is a very important step. Means the development of a polyp is a necessary but not sufficient step for the development of cancer. And we have a tool that allows us to look directly at the colon and identify any and all polyps, and remove them. And if you think about that, the implication is really nobody should die of colon cancer. If we accept screening at a high enough rate, it should certainly be far less than it is today. It shouldn’t be the third leading cause of cancer death. It shouldn’t kill 50,000 people a year.
– So on the topic of colon cancer, if someone were to visit you as a patient, what age do you recommend their first colonoscopy? And that’s assuming they’re willing to, you know, pay out of pocket if needed for it.
– So it depends on number of things. It certainly depends on family history and other personal risk factors, such as, you know, Crohn’s disease, ulcerative colitis, and things of that nature. But if we talk about a person who has no other risk factors and no family history, we still take a very aggressive posture and typically begin screening at 40, which is five years ahead of the current recommendation, and 10 years ahead of the last recommendation. Up until very recently, the recommendation for first colonoscopy was 50. That has been reduced to 45, which I think is a very good first step when you consider how many people under the age of 50 were dying from colon cancer.
– And then, the frequency, I imagine, also depends on what’s, of course, found in the colonoscopy?
– Yes, although, again, here’s where we are much more aggressive. We typically recommend screening no longer than every three years, but also depending on what’s found. So if you find a certain type of polyp that is indeed pre-cancerous, we would screen much more frequently. It also depends on the adequacy with which the endoscopist was able to visualize the colon. So when you do a colonoscopy, as anybody listening to this will recall, you go through something called a bowel prep. Now, fortunately, you know, I’m 50, so I’ve already had three of these things. Just in the last 10 years, the bowel preps have become much, much easier. In fact, the last one I did a year ago was a walk in the park, relative to the first one in terms of… You know, I was able to do it using a product where you only take 12 or 24 pills over the course of a day, and you have a much easier bowel prep. But when the endoscopist is in there, he or she basically makes a designation. It’s a scale, it’s a rating system, I believe it’s one to nine or zero to nine. I think it’s called the Boston Bowel Prep Score or something to that effect. But it’s basically, how well was I able to visualize the colon? And so we’re really looking for two things, right? To wait three years to do it again, we want no polyps and we want a perfect visualization of the colon. And if those conditions aren’t met, then we, you know, decide on what the next colonoscopy should be. I would note that, given that the biggest risks of colonoscopy are the bowel prep itself, which for people our age is not really a risk at all, just an inconvenience. But for older people, absolutely is a risk. There’s a risk of electrolyte abnormalance and dehydration. The sedation itself is a risk. Again, all of these risks are small, but none of them are zero. So you have risks that are associated with, you know, not breathing and things like that. And then, finally, there’s a risk of bleeding and perforation from the colonoscope. Given that you’re having a colonoscopy, you’re buying all of those risks. We generally recommend our patients undergo an upper endoscopy, to look at the esophagus and the stomach, as well, because cancer from the esophagus to the duodenum, while less common than cancer of the colon, is still collectively a relatively high-probability cancer, when taken together from mouth to duodenum, And therefore, given that it poses no additional risk to the patient, given that all the risk is baked into the colonoscopy, we generally recommend doing that as well. And surprisingly, we do at times find pre-cancerous lesions in the esophagus in people who maybe only report, you know, occasional heartburn, for example, which is a significant risk factor for something called Barrett’s esophagus, which is a pre-cancer of the esophagus.
– And you recommend that upper endoscopy at every colonoscopy if one can get it?
– It depends, you know? It’s impossible for me to take a blanket statement, even though I’m sounding like I’m sort of doing it now. Every case is different. But we are basically asking that question with every colonoscopy. “Should we do the upper endoscopy at the same time as well?”
– Got it. What was that product that you had such a wonderful bowel prep with? Because my most recent colonoscopy was a nasty liquid.
– Anything but.
– You know, it wasn’t a great experience.
– Yeah, the last one that I’ve done, and now this is what most of our patients do, it’s called SUTAB. I think it’s S-U-T-A-B. And I think just, basically, twice the day before, or, like, once the afternoon before, and once, you know, couple hours before bed, you’re taking like 12 tablets with a large amount of water. You know, probably 20 ounces of water or something like that. And yes, it’s an infinitely more pleasant experience, especially for people who don’t like the taste of a lot of these things. Which, again, going back 10 years ago, when you were drinking something called GoLYTELY, I mean, that stuff was an abomination, and the volume you had to consume was unbearable.
– I think that’s what I had, was the GoLYTELY, yeah.
– Yeah. They should ban that stuff.
– You had some specific… For people that haven’t had a colonoscopy before or, you know, are willing to change their endoscopist or GI specialist, what things should people be looking for in, you know, someone that’s gonna perform a colonoscopy on them? I remember in the book, you had some specific recommendations for things to look for.
– Yeah, we have a whole bunch of recommendations in the book. But, I mean, I think some of the big ones are I would always ask your endoscopist, “What’s your perforation rate?” In other words, it’s nice to tell me globally what the perforation rate is, but that’s a very misleading number because it also involves all sorts of patients, some of whom are very, very sick. So the real question is, “In outpatient elective colonoscopy, “what is your bleeding rate? “What is your perforation rate?” I would also ask, “What is your cecal intubation rate?” So, “How often are you getting into the cecum? “What is your typical endoscopy time? So, “What is the total time of scope?” And I provide in the book some metrics on what you’re kind of looking for, what would be considered ideal for this purpose.
– Great. Any other thoughts on colon cancer screening, before we move on to, perhaps, maybe breast and prostate screening?
– Yeah, I think the other thing I’d mention with that is that a really elegant thing to do on the off-years of colonoscopy is to do a stool-based test. So you can do like a fecal occult blood test, although that’s far less effective than the immunohistochemistry tests. So let’s just say you’re getting a colonoscopy every three or four years, if, on the years you’re not doing it, you’re doing a stool test that’s looking for tumor DNA, you’re at least looking for a signal in those off years. Now, again, that’s nowhere near as effective as a colonoscopy, but, of course, it poses no risk. So it’s, in my mind, kind of better than not doing anything in the off years.
– And if the stool test is positive, then-
– You would go straight to a colonoscopy. That’s right.
– Because, yeah, you point out that, despite maybe what people think, colon cancer can develop in as little as six months in some patients, right?
– Yeah, it’s a bit controversial. There have been case reports of that nature. Of course, the alternative explanation for that is that that cancer was there six months earlier, but somebody missed it. So the truth of it is, we actually don’t know what the time is to develop a colon cancer, right? Clearly, it’s way, way, way less than 10 years. So the idea that you would only do this every 10 years, to me, is absolutely insane. But, you know, maybe it’s one year, maybe it’s two years, maybe it’s three years. We just don’t know what it is. And when we see those case reports, it’s easy to be suspicious that, “Eh, it’s not that you really developed “a colon cancer in six months, “but it’s possible that it was missed six months ago.” And, either way, it reinforces the need to be vigilant.
– And for the stool test, is there one in particular that you tend to recommend more than others?
– I mean, again, it just comes kind of down to your budget, but we probably like Cologuard the most. And I can’t even remember how much it costs. I mean, put it this way, they cost significantly less than getting a colonoscopy.
– Yeah. Let’s talk about breast cancer. And again, maybe just start with your approach to breast cancer screening. If there’s, you know, a particular age? I know every patient’s different, but if there’s not a strong family history of breast cancer, is there a particular age that you recommend starting screening for breast cancer?
– Well, again, breast cancer is pretty common. A woman’s lifetime risk of breast cancer, at least in terms of having it, not necessarily dying from it, is high enough that I think you have to approach every woman as though she’s at risk. And clearly, family history here is a very valuable tool for, at least, a woman who has not been adopted, right? So if you have a woman who’s not adopted, and whom we can look at her mom, her grandmother, both sides, her aunts on both sides, if we can start to get some insights there, that can really shape our thinking. So if we’re, again, let’s say, dealing with somebody who does not have a family history of breast cancer… Well, I should say even more. There’s more detail to it that I think is kind of maybe beyond the scope of our discussion, but there’s more nuance around this, right? So sort of, if breast cancer occurred in family members, it’s also important to understand if it was pre or post-menopause. So early-life versus late-life, breast cancer kind of gives us a slightly different algorithm for how we screen. We then look at some other very personal factors. For example, a woman’s breast tissue, how dense is it, right? So the denser the breast tissue, the greater the likelihood that you’re going to miss a breast cancer on screening. I think the most important thing… And I wanna just be clear, like, you know, there are people for whom this is their specialty, and I would think that they’re far more knowledgeable about this than me. So I’m only talking about this through the lens of how we think about it with our patients. But, you know, I think there’s no form of cancer screening where the idea of stacking different modalities is more important than in the breast. So, to be clear, I don’t think there is any single modality that is sufficient for screening breast cancer. Every modality has a strength and weakness, and the good news is they are opposing. So, for example, mammography is very good at picking up calcified lesions. So lesions that have, you know, little specks of calcium in them. And certainly, cancers can have little specks of calcium in them. That tends to be later in life. So younger women don’t necessarily get as many calcific breast cancers. It also tends to struggle with dense breast tissue. So you’re gonna get a lot of false negatives and a lot of false positives, frankly, in a low-prevalence population of young women. Conversely, if you look at something like MRI, MRI has much more sensitivity to pick up breast cancer, although it actually has kind of low specificity, and it tends to miss all calcified lesions, unless they’re really, really big. So it has an enormous blind spot to the very thing that mammography is very good at. And then ultrasound offers, you know, advantages and disadvantages as well. So the first thing I would say is whenever you decide to start screening, you have to be thinking about using at least two modalities. So I think mammogram should be an automatic for every woman. And then, I think the question based on risk should be, is ultrasound the right thing to do in concert with it, or should it be MRI? And even within MRI, there’s different ways to do it. So the gold standard would be something called multiparametric MRI, where you’re using contrast, and something called diffusion-weighted imaging, which I think I explained in the book why that’s such a special tool to enhance MRI.
– When you stack those modalities, do you typically stagger them out? You know, maybe get a mammography test done one year and then an MRI done the following year? Or do you tend to get them at the same time, and do they complement each other kind of in real-time?
– Yeah, great question. There’s no right answer to this. It depends on the patient. So for some patients, we stagger everything by six months. So they’ll do an MRI every year and a mammogram every year, but they’ll be offset by six months. So they’re doing a form of screening every six months. That would be kind of a higher-risk woman. For other women, you might do mammography every year and MRI every two years. So there’s an endless permutation in here. And, you know, again, we don’t have level one evidence telling us what the right answer is, but, of course, level one evidence don’t really apply to this type of screening, for the reasons I talk about in the book. Which is, you know, level one evidence are also going to concern themselves with cost, societal cost, or cost of screening. I think that’s a totally valid concern, but it’s not one that I concern myself or my patients with. Which is, we’re asking the question that’s slightly less constrained, which is, if you ignore cost, what is the right approach to screening? And there, you only have to concern yourself with harm, right? False positives, psychological harm, and, you know, opportunity cost. But we don’t really need to think about monetary cost. Which, again, it’s important. It absolutely matters at the societal level if somebody else is paying. But I think it’s a personal choice for anybody who’s gonna pay for themselves.
– Along those lines, genetic testing for genes that may increase the risk of breast cancer, do you typically recommend that?
– We do it in select patients? So if the family history comes up completely stone-cold negative, we typically do not do it. If it comes up a little suspect, we certainly do. Obviously, one of the genes everybody’s looking for is the family BRCA genes. Usually, it’s pretty obvious when that’s the case, just from the family history, but you would absolutely wanna confirm that genetically. But, you know, the real edge cases are the ones that are probably more interesting, which is not a BRCA case, which is usually quite obvious, but sort of a non-BRCA case when there are other less, you know, further from being deterministic genes. And BRCA, by the way, is not necessarily deterministic, but you have genes that are just more subtle increases in risk. Again, there are reasons to do this both from a financial perspective, right? So once you have a gene that places you at greater risk, obviously, more of your care is covered. So that’s very important. It also has significance in terms of, you know, planning and expectations around having kids. You know, if a woman has one of these genes, she’s gonna be much more on guard if she has a child and can sort of think through those things. And, of course, ultimately, if the risk is significant enough, a woman can elect to do something much more aggressive than screen, which is to prophylactically undergo a mastectomy and just eliminate the source of the tumor before a tumor forms. And interestingly, there are a number of cases where women prophylactically do get mastectomies in breasts that otherwise appear normal, only to find out that they actually do have microscopic foci of tumor at the time of mastectomy.
– Any other thoughts on breast cancer screening before we move on to prostate cancer screening?
– I think one other thing I would just say on breast cancer is the other tool that we do use here, and it’s a very emerging tool, is that of the liquid biopsy. So liquid biopsies are still in their infancy, but they are already showing promise. And breast cancer is an example where, if you just look at the data superficially, you would probably convince yourself that they’re not very helpful. But if you look at the data more deeply, and I cite an example of this in the book, I think you start to realize that liquid biopsy becomes yet another tool that we should include in this. So superficially, the data for early detection of breast cancer with a test called the Galleri test by a company called GRAIL, suggests that the sensitivity is very low, something on the order of 20% for stage one and stage two breast cancer, while the specificity is very high, north of 99%. About 99.5%. So low sensitivity, high specificity means if a tumor is there, you might not see it. But if no tumor is there, you’re gonna get it right. That’s effectively what that means. Well, again, that doesn’t seem like it’s very helpful if you’re trying to screen for a cancer. But when you look more closely at the data, and you segregate out the breast cancers by type, and you divide them between hormone positive and hormone negative. So in breast cancer, a lot of the prognosis and treatment comes down to whether the breast cancer is positive for estrogen and progesterone receptors and another receptor called HER2/neu. So if you look at the triple positive, which is all three receptors positive versus the triple negatives, you have a very different story. The ability of the liquid biopsy to detect the triple negative at an early tiny stage tumor is over three times higher than it is for the triple positive. The implication here is that the liquid biopsy is much better at detecting more aggressive tumors, and, therefore, it might suggest that the stage one, stage two triple-positive tumors aren’t going to kill you if you catch them at that stage, which you’re gonna catch with other means, because they aren’t spreading. These tests are looking for cell-free DNA. Whereas you are catching the more aggressive tumors because they’re already spreading by the time they’re stage two. So that’s just another wrinkle that I think has to always be considered as we kind of think about how to incorporate liquid biopsies into this.
– And for people that are new to that term, the Galleri test that you mentioned, if someone wanted to get that test done, what’s the process of actually attaining that?
– It has to be ordered by a physician, to my knowledge. I don’t believe that they do a direct-to-consumer. I could be wrong. I mean, I have no affiliation with this company. So, in our case, you know, when we choose to order that, we are the ones that order that for our patients. And it’s a blood test. So, you know, it’s a test that takes two tubes of blood and returns a result in a relatively short period of time, usually within two weeks or so.
– Yep. And you mentioned that it basically gives you information about a couple different things. A, do you have a cancer present, potentially, and B, where is it coming from in the body? And you also mentioned, maybe you could speak to this a bit, and correct me if I have this right, that your opinion is, it’s not a great just broad screening tool for cancer. It should be used, in general, for specific purposes or to stack with other screening modalities?
– Yeah, I mean, I would say that we do use it as a pan-cancer tool, but I’m generally not going to just rely on it by itself. So I’m not going to just say, “We’ll do the test, “and if it comes back negative, “we don’t have to do anything else.” I don’t have enough confidence in any test to say that, including a whole-body MRI. So I view everything as a stacking, you know, optimization problem.
– Do you see the technology advancing with liquid biopsies to the point where maybe we would be able to say with more confidence? I guess that what really needs to happen is the false positive rate would need to drop significantly on the test, right?
– Yeah. I think the problem with liquid biopsies, it’s a very important conceptual issue we have to wrap our heads around, which is, what is a false negative? What is a false positive? Like, what do they actually mean? Because when a person gets an MRI or a mammogram or a colonoscopy… Well, let’s take colonoscopy out of it. So colonoscopy, you are looking directly at something. There is no false positive, right? There’s no false positives in colonoscopies. There’s false negatives if the bowel prep isn’t good or the endoscopist just missed it, but there’s no such thing as a false positive. But if you’re looking at an MRI or a mammogram, a false positive means you’re looking at a set of pixels that are meant to represent something that is happening in the body that is an anatomic feature, right? It is purely an anatomic test. A liquid biopsy is not an anatomic test. In some ways, I don’t have a good word for it, but it’s a biological test, maybe, right? It’s testing the ability of that cell to escape its primary location such that it’s shedding cell-free DNA. We have to wrap our heads around what that means and what the implications are for screening, and I don’t think we fully have yet. And that’s why I don’t think it will ever make sense to rely on a biological or functional assay, in exclusion of an anatomical assay or vice versa. I think we just wanna come back to all of these things of the time, because it also increases the fidelity of the test, right? What we don’t wanna do… I mean, we have to accept the fact that if we’re gonna be aggressively screening, we’re gonna find a lot of false positives. It’s impossible to have 100% sensitivity and 100% specificity. It’s impossible. So you can plug those numbers into a spreadsheet, and it will tell you that for any prevalence of cancer, even a cancer that only exists in 1% of the population, you’ll have 100% positive predictive value and 100% negative predictive value. Meaning every time it’s positive, it’s truly positive. Every time it’s negative, it’s truly negative. But nothing comes close to that, right? So MRI has almost 100% sensitivity, but its specificity is abysmal. Liquid biopsies, the opposite. Its specificity is almost 100%, its sensitivity is abysmal. Now, here’s the thing. It is not the case that when you add two tests, you add their sensitivity and specificity. So it’s mathematics behind it are more complicated. But clearly, the more tests you add, the more shots you’re getting on goal to pressure test what you’re seeing.
– Speaking of sensitivity and specificity, I like an analogy that you’ve used before of a metal detector with regard to these tests. I mean, they can really be set however the test makers want to set them. So could you kind of explain that analogy and how it fits with liquid biopsies, for example?
– Sure, so I’m sure people have experienced this all the time, right? It’s like you’re passing through an airport metal detector, and it goes off, and you think to yourself, “Dude, I’m wearing the exact same thing “I was wearing three days ago “when I went to the metal detector at the other airport, “and it didn’t go off. “How is that the case? “Like, did I somehow suddenly take on “a whole bunch of metal?” No, the sensitivity of that metal detector has just been set to be higher, or lower, depending on how you wanna think about it. So, in other words, it’s going to kick off at a lower threshold. Okay, so let’s now play the thought experiment, right? So put yourself in the minds of TSA. So you get to set the sensitivity on the device. You get to say what is a positive. So sensitivity is the definition of the true positive rate. So if you set that thing to be very, very twitchy, the likelihood that anybody will get through who actually has metal, you can make that number exceedingly low. But what’s the problem with that? The problem with that is that most of the people going through who don’t have metal are still getting stopped. So, you know, you basically create a log jam problem where you’re creating a whole bunch of distress for no reason. But in fairness, no bad guys are getting through. Conversely, you can say, “All right, fine, fine, fine, fine. “Let’s set the bar really, really high.” So anyone that we catch is a bad guy, and we’re not gonna create any distress or false positive, but the problem is there’s absolutely gonna be some bad guys that get through. So if you set it such that, “I’m gonna catch anybody carrying an 18-inch knife “or a gun,” that’s fine. But maybe somebody walking through with, you know, a six-inch knife doesn’t have enough metal to trigger it. So that’s basically, as you say, kind of the decision everybody has to make as they work through how to tune a screening test. Are you tuning it more towards no false positives or more towards no false negatives? And sometimes that’s the nature of the test. So for example, an MRI, because of the resolution that it can produce, it’s generally geared towards higher sensitivity. It’s gonna overcall things, especially in glandular tissue, like the thyroid gland and the pancreas, and things like that. But in a liquid biopsy, it’s 100% at the discretion of the scientists as they tune the algorithm.
– Makes sense. Okay, getting back to prostate cancer screening. This is one that, you know, most people watching this have heard the PSA test for prostate. But could you explain what PSA is and how we can do better than just look at the PSA number alone for prostate screening?
– So, PSA stands for prostate-specific antigen, and it’s a protein that is made or an antigen that’s made by cells in the prostate. And obviously, it’s not made by other cells, that’s why it’s prostate-specific. This is a biomarker that you can measure in the blood. And this value is proportional to the size of the prostate gland, but it also comes out disproportionately when a person has prostate cancer. So we tend to think of the prostate in either, you know, milliliters or grams. We can estimate the size of it pretty well on an ultrasound or on an MRI. So if you took two people who had the same size prostate, so let’s say a 25-gram prostate, which is a normal-size prostate, you know, you would expect them both to have a relatively low PSA, probably at or below one. Let’s just say it’s one. But if one of those people, all of a sudden, has a PSA of four or five, even though his prostate isn’t significantly larger, you would certainly be worried about the risk of prostate cancer. Because, again, once those cells make the transition to becoming cancer cells, they’re going to secrete more and more of this prostate-specific antigen. And historically, prostate-specific antigen, or PSA, was a screening test that was done for men. It was always one that created a lot of consternation within the community because it was a test that when used by itself, had a lot of false positives, and, frankly, a lot of false negatives. So false positives meant there were a lot of men who were, you know, showing up with a PSA value that was higher than you would’ve expected based on, you know, their age, for example. And the next step was to do a biopsy of their prostate gland to make sure they didn’t have cancer. And lo and behold, they wouldn’t have cancer, and you’ve just subjected them to a pretty aggressive procedure. You know, a transrectal biopsy of the prostate is not a benign procedure. Not having had one, but certainly having spoken to many people who have, I’ve never heard anybody say, “That was pleasant.” And not without complications, by the way. So the question is, how could you make the predictive value of the PSA better? This, by the way, is another question of, where do you set the bar? So let’s go back and think about this through the lens of your metal detector. You could say, “We are not going to biopsy anybody “below a PSA of 10.” And if that’s the case, outside of guys with prostatitis, you’re only gonna be biopsying people with cancer, but you’re gonna miss a lot of people with cancer too. You’re not gonna have false positives, but you’re gonna have a lot of false negatives. If you say, “Okay, we’re gonna biopsy everybody “who’s over three,” oh, my God, you’re probably not gonna miss many cancers, but there’s a lot of people getting biopsies who shouldn’t get them. So today, what we do is we don’t just look at the PSA, we look at several other metrics. We look at something called free PSA, which is the percent of PSA that is unbound, that’s not being bound to other carrier proteins. And so the percent free also gives us a clue as to whether or not this is a prostate cancer or not. We look at something called PSA density, which is the PSA value normalized to the size of the prostate. We look at something called PSA velocity, which is the rate of change of PSA value over time. All of these things, so higher PSA velocities, higher PSA densities, differences in percent free PSA, add color beyond just PSA and will give us a much earlier indication as to whether something is significant. In which case, we can, depending on the PSA value, either move to another type of blood test called a 4K Test, which is kind of like another liquid biopsy for prostate, but it’s specific to prostate, or move directly to a multiparametric MRI, which is very similar to that multiparametric MRI I talked about for breast tissue, where you’re looking at these different types of pictures, so different types of images of the MRI, T1, T2, diffusion-weighted imaging, et cetera, with and without contrast. So where we basically are now is very few men are undergoing unnecessary biopsies. In fact, I don’t think in the last 10 years I’ve had a single patient undergo a prostate biopsy that did not find cancer. So the implication is, by the time we are sending a patient for a biopsy today, we know he has cancer, it’s just a question of how aggressive. Now, some of those men come back with a cancer that is not very aggressive, and the collective decision of the urologist and the patient is to wait a year and biopsy again. And in one of those cases, I can… You know, I just think about a patient very recently, there was enough of a change in the histology over a year that they said, “Enough is enough, “we’re gonna do surgery now.” In other cases, the answer is, “Let’s wait another year and do it.” Or compare it to, you know, other characteristics of the MRI. So the point is, you know, this has largely become an issue where we are less doing these biopsies with low probability, you know, thinking in terms of outcomes.
– These additional PSA blood tests that can be done; the PSA velocity, density, and free PSA. Or what was it? Yeah, the free PSA.
– 4K. Yeah.
– And then the 4K, as well.
– So when you order a PSA test, a lab will typically default into a free PSA. They’ll reflex a free PSA test if it’s over three, typically. I forget, is it three or four? But usually, with a high enough PSA, I think, over three, you can automatically just get the free PSA. The other ones, you actually have to manually calculate. The lab won’t tell you the density, you have to have had an ultrasound or some other imaging of the prostate to know its size to then calculate the prostate density. And similarly, you have to keep track of the PSA values and plug them in. They have online calculators that’ll do this for you, where you put in historical PSA data with time, and it will tell you the PSA velocity.
– Got it. So that gets at my next question is… I know this is something that you do at your practice with your patients. Is are any of these additional parameters, beyond just the simple PSA test mainstream in family medicine clinics across the United States, for example, to your knowledge?
– It’s a good question. I mean, unfortunately, we know that there are lots of people who are falling through the cracks. So, you know, someone who works with me, actually, meaning one of my colleagues, his dad was at his doctor and, you know, he had a PSA level, and it wasn’t particularly alarming, and his doctor wasn’t concerned. And the colleague of mine said, “Well, let me do a double check on that,” and ran it through the PSA velocity check, and actually, the PSA velocity was higher than 0.45. So that’s generally the cutoff. Meaning anything that’s growing more than 0.5, the units aren’t important, 0.45 units per year, anything that’s growing at a rate beyond that is alarming. And even though the absolute value of his PSA wasn’t that high, the velocity was. And so he went back to his dad, and said, “Hey, you need to go and get more testing done. “You probably need a biopsy or, at least, an MRI.” And his doctor said, “No, he doesn’t. This is totally fine.” And so, you know, this colleague of mine just told his dad, “We’re gonna go around your doc “and just go and pay and get an MRI.” They did, the MRI indeed showed that he had a cancer. He got a biopsy, it was cancer. He’s already had his prostate taken out.
– [Kyle] Wow.
– So, you know, his son saved his life. And it’s disappointing that the doctor was completely unwilling to even acknowledge this. So, you know, I’m guessing if that happened once, it’s gonna happen a few times. And unfortunately, I think what the lesson is there is you, as the patient, probably have to be the owner of this process, and you really can’t rely on anybody else. Now, I think that particular doctor had an arrogance about him that’s sort of deplorable, but the reality of it is even a well-meaning doctor, I think, can miss something or maybe just isn’t keeping up with this literature. So, I think, you know, everybody has to kind of take ownership over this problem for themselves, which is unfortunate because, in an ideal world, that’s… You know, I shouldn’t have to take ownership of my car when I take it to a mechanic. That’s why I’m taking it to a mechanic. But unfortunately, I think, you know, that might be the case.
– How common is prostate cancer in men? And, you know, I think many watching this have heard that many people die with prostate cancer, not necessarily from it. So how do you explain the overall risk of prostate cancer to your patients?
– Yeah, no, I think that’s exactly what I say. Is virtually every man will die with it, fortunately, not too many die from it, but it is still the second leading cause of cancer death in a man, only behind lung cancer. So, you know, it’s not a particularly lethal cancer, compared to, say, pancreatic cancer or, you know, certain types of brain cancer or lung cancer. I mean, those are incredibly lethal, meaning once you get it, you’re very likely to die. That’s not the case with prostate cancer. But because so many men get it, and even though the lethality is not that high, the absolute numbers are pretty devastating. Think about COVID, right? Virtually nobody who got COVID died of it, but because everybody got it, the total death toll actually was pretty high, right?
– You mentioned lung cancer there being the number one killer. We know it’s a huge risk for people that smoke, but what is the risk for people that have never smoked?
– Yeah. Sadly, it’s not zero, right? So 15% of people who develop lung cancer are never smokers. And sadly, we see that disproportionately in women over men, and we see that women non-smokers are the fastest segment of lung cancer growth. Again, that’s a very sobering statistic for which we have no great explanation. I wrote an article on this in our blog newsletter several months ago. If people are interested, they can go back. I mean, Katherine, who’s the analyst that I worked on this with, you know, I think we went kind of back and forth on some of the why’s. You know, is it something to do with estrogen? Is it something to do with, you know, different types of gases that women might be more exposed to? I mean, the short answer is I don’t think we really have a great answer. There’s clearly some difference, either genetic or otherwise, that is pointing to this susceptibility that non-smoking women appear to have. And again, disproportionately, it’s an adenocarcinoma of the lung that is afflicting them, and it’s very frightening. Because, again, nobody’s thinking about lung cancer screening in the non-smoker. It wouldn’t cross your mind to take a healthy 40-year-old woman who’s never smoked and screen her for lung cancer. That’s just the furthest thing from your mind. And we have a patient who has survived an aggressive adenocarcinoma of the lung, only because she was so lucky in that she had a calcium scan, a special CT of the heart, to look for calcification of the heart, and it just happened to pick up a small cancer. And I think had that cancer been caught a year later, you know, I think there’s a good chance it would’ve been too late.
– This kind of ties in with lung cancer, potentially. You mentioned earlier MRI screening for cancer. Taking someone who doesn’t have signs or symptoms of cancer, and putting them on an MRI scanner, using a special technique that you mentioned, diffusion-weighted imaging. Can you explain your recommendations around that to your patients? The value that you see in that type of screening?
– So, again, MRI has its strengths and its weaknesses. And its greatest strengths are it has no radiation. So it poses no harm to the individual, unlike, say, a CAT scan or a PET scan, which have tons of radiation and should never be used for general screening purposes, with one exception that we can talk about later. And it has a very, very high sensitivity, meaning if a cancer is there, an MRI is pretty likely to see it. Now, there’s things it’ll miss. This is only within the types of cancers that it can see. It’s not great for any of those outside-the-body cancers. So by the time an MRI is picking up a colon cancer or an esophageal cancer, it should have been picked up years ago on an endoscopy. So you do not wanna rely on this for diagnosing cervical cancer or endometrial cancer. Those are other examples, by the way, of outside-the-body cancers, right? You can look directly at the cervix, directly at the uterus, et cetera. So anything that can be looked at outside the body, we’re gonna do that. But if you take away those cancers, yeah, it’s a high sensitivity test, but it’s a very low specificity test, meaning it’s just not good at differentiating between cancer and non-cancer in certain tissues, namely glandular tissue. So, again, MRI is the metal detector that’s beeping all the freaking time. It just doesn’t stop beeping. It’s the most annoying metal detector you’re ever gonna see. So you’re stopping a whole lot of people that are posing no threat to the airplane. So in an effort to make that better, a technique that was developed to look at strokes is now being applied to the whole body. This technique is known as diffusion-weighted imaging with background subtraction, but we just abbreviate it to DWI. What this technique does… And will not explain this in great detail because to do so, I would actually need to explain how MRIs work and how the pulsing of the magnets makes protons move, and, honestly, I just think most people don’t want to get into that level of detail. But if you sort of just try to suspend disbelief for a moment. The way an MRI is basically working is it’s working by detecting the movement of protons. That’s effectively what an MRI’s shtick is. So a CT scan, totally different shtick, right? A CT scan is shining electrons through something, and on the backside of that thing, it’s collecting how many electrons hit it and it’s imputing the density of the thing it went through based on the collection of electrons. MRI, totally different. It’s using very powerful magnets and making protons move. And depending on how it pulses the protons, it’s measuring different aspects of the movement of protons. So protons, of course, are ubiquitous in fat and water. Proton is hydrogen, right? So, H2O and the CH group in a fat molecule. So we’re full of protons. It’s the most ubiquitous atom in our body. And the diffusion-weighted imaging trick is to pulse water, and basically look to see how long it takes to move again. And this works really well to determine how firm a piece of tissue is. So in the brain, when a person’s potentially had a stroke, you can take a look and see the firmness of the tissue, even if there’s no bleeding in the area. Now, this works in the brain because the head doesn’t move. The head is the easiest thing to stabilize in an MRI scanner. And so the frequency with which they would ping these things was typically, you know, 50 microseconds. And that was quick enough that they could still see the artifact or the movement artifact. To do that in the body is much harder. 50 microseconds is not fast enough to actually get a good signal in the body because you can’t limit the movement of the body as much. The body won’t stay as still as the head. So there are companies that are working on using faster and faster software to get that time down to 20 and even 10 microseconds. And at that rate, the diffusion-weighted imagining is starting to work pretty well in the body. And you can sort of think of it as a visual lump detector. It’s able to concentrate the signal, the darkness of the digital signal, around the firmness of the tissue. And that is serving as an effective way, one effective way, to increase the specificity of an otherwise high sensitivity, low specificity test.
– Well, I’ll reveal that I am thankful for this technology because that’s what actually caught my cancer. That caught my Hodgkin lymphoma. Company called Prenuvo I know is offering them. Are they the only one right now that offers the full body screening for this purpose?
– Prenuvo is probably the best MRI today at doing this detection. Now, there are other companies that do it, but they’re licensing the Prenuvo technology. But, yeah, at this time, we are only having our patients get scanned in a Prenuvo scanner, either at Prenuvo or at a facility that uses a Prenuvo scanner.
– And hopefully, someday, insurance will cover this type of screening because, as you mentioned, there’s potentially a lot of value in it. But right now, as far as you know, this has to be out of pocket for probably everyone?
– 100% out of pocket. Yeah. And what I tell patients is, “Don’t do this if you’re not willing “to deal with the very high probability “that something will be found that is not cancer, “but will require additional work.” So, you know, I don’t have the exact numbers, but I would say at least 20% of the time we send a patient for one of these scans, we, you know, get the news that, “Yeah, there’s almost assuredly nothing here, “but there’s this other thing. “There’s this potential…” And by the way, sometimes these are important things. Like you catch aneurysms. You know, an aneurysm in the brain or in the pancreas can be lethal if not caught. So sometimes you catch these other things, and you go ahead and you fix them. So all comers, we’re seeing, you know, about a 0.7% aneurysm catch rate. Now, probably a number of those will go on to be just fine if you did nothing about them, but a subset of those have lethal potential. But more likely, you’re catching these kind of clinically insignificant other artifacts that you do need to chase and pursue. And as a result of that, I don’t know, I would say maybe 15% of our patients just elect not to do a whole body MRI for that reason, which is they don’t feel like their constitution is gonna, you know, deal well with the following months of uncertainty as these other things are chased down. And so I think that’s a wise and informed decision for them. I just wanna make sure we don’t get to the point where people are doing this type of screening without having that discussion, and understanding that, “Hey, you know, “there’s a chance we’re going down a rabbit hole here. “If you’re not ready to go down that rabbit hole, “don’t get on the ride.”
– Yeah. Okay. Shifting to… And you already mentioned this briefly, but you mentioned cancer is probably the least well-understood as far as what we can do to prevent it. But you also mentioned that exercise is perhaps the greatest longevity drug. So do we have evidence, at this time, that exercise can help prevent cancer? And that’s decoupling exercise from, you know, the benefits it might have on someone’s, you know, weight. You know, taking someone from obese to not obese, I mean, we know that that can be helpful for cancer. But just can exercise alone help prevent cancer to our knowledge?
– Yeah, I think there’s very good evidence that it can, right? When you think about some of the things that exercise is doing. So if you think about the metabolic benefits of exercise, it certainly far transcends weight loss. You know, muscle is by far the most important sink for glucose. And so, insulin-sensitive muscles are equivalent to insulin-sensitive people. You can’t be insulin sensitive without having insulin-sensitive muscles. You can’t have insulin-sensitive muscles without exercising once you reach a certain age. I mean, you know, a youngster maybe. But certainly, by the time you’re in your 20s and 30s, you have to be exercising to maintain true insulin sensitivity. And that may be the single most important factor there is. But going beyond that, you know, exercise does a lot of things, right? It creates a lot of myokines, a lot of chemical signals that do various things throughout the body, including reducing chronic inflammation. And I think chronic inflammation is one of the impediments of the immune system. And so, if being insulin sensitive cuts down on the growth factors, having less inflammation enhances the immune system. And you could certainly make the case, and I would make the case, that those are probably two of the most important things at our disposal when it comes to reducing our risk of cancer.
– Excellent. Any other cancer prevention strategies, besides the ones that you’ve already highlighted, that one should consider? Of course, avoiding detrimental things, like smoking, aside.
– Yeah, I think those are really the big ones. I mean, there are things we don’t understand. You know, we probably don’t understand exactly the role that stress is playing on cancer, but I just have to think that there is a legitimate risk there through the mediation of hypercortisolemia and excessive glucocorticoids on the immune system as well. So I think, you know, just some level of immune system and immune cell exhaustion as we age, is probably equally responsible for the exponential increase in cancer as we age, right? I mean, part of that I think is more time to accumulate mutations, and mutations are the core thing that are driving cancer. But I also think at least half of the equation is that our immune system is getting weaker as we age. And that’s actually one of the things where… You know, if I think about all of the sci-fi things that are going on out there, the one that I would most want to see come to fruition would be addressing the exhaustion of the immune system. So if we could sort of manipulate the epigenome of T-cells, specifically, and turn old T-cells into younger T-cells again, that would have a profound impact, I believe, on cancer treatment.
– Any other cancer screening modalities that we missed? We talked about lung, colon, breast, prostate. You mentioned screening for cervical cancer, briefly. Skin checks you mentioned. Any other ones that we’re missing that we have the opportunity to screen for?
– Yeah, I mean, there certainly are, and it’s always gonna be case by case, right? So, for example, in a person with a history, or a family history of bladder cancer, or in someone who has a personal history of smoking, we would even recommend cystoscopy. For people who are former smokers, we also add low-dose CT scan to the lung MRI. The MRI of the lung with diffusion-weighted imaging, is equal, probably, to the low-dose CT for adenocarcinoma. But when you’re talking about small cell carcinoma, squamous cell carcinoma, or large cell, which are more common in smokers, I think you’re getting more benefit from the low-dose CT scan. So we’re doing a low-dose CT of the chest annually in former smokers as well.
– And then what about just genetic testing for your patients? Getting their whole genome sequenced with something like 23andMe or one of those companies?
– I mean, I think, every one of these things has its place, but you have to know what you’re kind of looking for before you do it. I mean, again, if a person’s been adopted, then I think there might be some benefit in doing it. You might come up with something that you really didn’t know, but you’d be amazed what a very thorough family history can accomplish for a person, at least when it comes to cancer. You know, I think we probably get more insight genetic testing on some of the other diseases. But with cancer, at this point in time, we generally don’t routinely screen, and we use the screening selectively based on an individual’s history.
– Okay, well, to finish up, any other final thoughts on cancer screening or prevention?
– No, I think, unfortunately, you know, prevention and screening have to be our main strategies today. I think the treatment landscape is, you know, still kind of lacking relative to cardiovascular disease, though it’s further ahead than neurodegenerative disease. But, you know, personally, I remain incredibly optimistic about what’s going to come as far as expanding the capacity of immunotherapy. Again, I said something earlier that might have gone over some people’s heads because I just sort of mentioned it in passing, but we now know that 80% of solid organ tumors have novel neoantigens. Meaning 80% of the cancers that people think about when they think about getting cancers that kill, have enough antigen that a person’s own immune system can recognize it. The problem is not enough of the immune cell can recognize it, and that’s why, ultimately, the cancer wins. So we’re playing a game of tug of war right now, and the good news is we at least have some guys that can hold onto the rope. The problem is we don’t have enough in most cases. So we have to figure out a way to increase the number of T-cells that can expand to meet that need once they recognize a cancer cell. Because I do believe that, ultimately, there is no therapy that’s going to rival that of immunotherapy.
– Well, Dr. Attia, thanks so much for your time today. Thanks for your fantastic book. I really enjoyed reading that. And you systematically go through many of the things that we talked about today, so really appreciate all the time you spent on that. And for people that haven’t already, please check out Dr. Attia’s podcast, “The Drive.” And you can find him online at PeterAttia.com, is that correct?
– Yep. “PeterAttiaMD,” actually.
– PeterAttiaMD.com and then Early Medical too, which is an exciting new website that you’re working on.
– Thanks again, Dr. Attia.
– Thanks so much. Yeah, appreciate you having me.