The Peter Attia Drive - Qualy #53 - Screening for prostate cancer

Episode Date: November 5, 2019

Today's episode of The Qualys is from podcast #39 – Ted Schaeffer, M.D., Ph.D.: How to catch, treat, and survive prostate cancer.     The Qualys is a subscriber-exclusive podcast, released Tuesday through Friday, and published exclusively on our private, subscriber-only podcast feed. Qualys is short-hand for “qualifying round,” which are typically the fastest laps driven in a race car—done before the race to determine starting position on the grid for race day. The Qualys are short (i.e., “fast”), typically less than ten minutes, and highlight the best questions, topics, and tactics discussed on The Drive. Occasionally, we will also release an episode on the main podcast feed for non-subscribers, which is what you are listening to now. Learn more: https://peterattiamd.com/podcast/qualys/   Subscribe to receive access to all episodes of The Qualys (and other exclusive subscriber-only content): https://peterattiamd.com/subscribe/  Connect with Peter on Facebook.com/PeterAttiaMD | Twitter.com/PeterAttiaMD | Instagram.com/PeterAttiaMD

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So without further delay, I hope you enjoy today's quality. [♪ OUTRO MUSIC PLAYING [♪ [♪ OUTRO MUSIC PLAYING [♪ [♪ OUTRO MUSIC PLAYING [♪ [♪ OUTRO MUSIC PLAYING [♪ [♪ OUTRO MUSIC PLAYING [♪ [♪ OUTRO MUSIC PLAYING [♪ [♪ OUTRO MUSIC PLAYING [♪ [♪ OUTRO MUSIC PLAYING [♪ [♪ OUTRO MUSIC PLAYING [♪ [♪ OUTRO MUSIC PLAYING [♪ [♪ OUTRO MUSIC PLAYING [♪ [♪ OUTRO MUSIC PLAYING [♪ [♪ OUTRO MUSIC PLAYING [♪ [♪ OUTRO MUSIC PLAYING [♪ [♪ OUTRO MUSIC PLAYING [♪ [♪ OUTRO MUSIC PLAYING [♪ [♪ OUTRO MUSIC PLAYING [♪ [♪ OUTRO MUSIC PLAYING [♪ [♪ OUTRO MUSIC PLAYING [♪ [♪ OUTRO MUSIC PLAYING [♪ [♪ OUTRO MUSIC PLAYING [♪ [♪ OUTRO MUSIC PLAYING [♪ [♪ OUTRO MUSIC PLAYING [♪ [♪ OUTRO MUSIC PLAYING [♪ [♪ OUTRO MUSIC PLAYING [♪ [♪ OUTRO MUSIC PLAYING [♪ [♪ OUTRO MUSIC PLAYING [♪ OUTRO MUSIC [♪ [♪ OUTRO MUSIC [♪ [♪ OUTRO MUSIC [♪ [♪ OUTRO MUSIC [♪ [♪ OUTRO MUSIC [♪ [♪ OUTRO MUSIC [♪ [♪ OUTRO MUSIC [♪ OUTRO MUSIC [♪ [♪ OUTRO MUSIC [♪ [♪ OUT [♪ OUTRO MUSIC [♪ [♪ OUTRO MUSIC [♪ [♪ OUTRO MUSIC [♪ OUTRO MUSIC [♪ OUTRO MUSIC [♪ [♪ OUTRO MUSIC [♪ [♪ OUTRO [♪ [♪ [♪ [♪ [♪ [♪ [♪ OUTRO [♪ [♪ OUT [♪ OUTRO [♪ OUTRO [♪ OUT [♪ OUT So without further delay, I hope you enjoy today's quality. Let's talk a little bit about prostate cancer because it's not a cancer that comes without its controversy. So, let's start with the biggest kind of risk, or certainly one of the biggest controversies, or things that would confuse the lay person because about every year the advice changes on this thing called PSA. So, what is the prostate specific antigen? PSA is a protein. It's made by the prostate,

and its normal function is to liquefy semen. So it's highly expressed in the process. So the way I explained the prostate to people, it's the best analogy I can come up with is if you think about it like a sewer system, you have the main sewer leaving the city. That's the urethra. That's the tube that we normally urinate through. But this channel also delivers semen out the tip of the penis. Off this main sewer are slightly smaller sewers that go to different neighborhoods. Within the neighborhood, there's a sewer that comes out of the individual house.

And the individual houses in this analogy are prostate epithelial cells. They make components of the semen. And the semen is used to give nutrients to the sperm while it's trying to fertilize an egg, to enable the sperm to penetrate the cervical mucus, these different functions. PSA is a protein that breaks down the semen and liquefies it and people think it's an important for for this whole process of fertilizing an egg. So that's what it does. And if you look in the semen, the PSA numbers are 100 million per ml. I mean the numbers the amount of this protein in the semen is astronomically high. So that's what it is, that's what it does.

So how do we use it as a tool to screen for prostate cancer? Well, we check the values of the PSA in the blood. So since the prostate is a sexual gland, if you check the values of a PSA and a eight-year-old boy, it would be zero. Because there's no testosterone in that boy, there's no sexual development in that boy, and therefore there's, you know, I mean, there's some, but effectively no. Before puberty, there's very little levels of testosterone, there's no effectively prostate epithelium, and there's no PSA. As a boy goes through puberty to become a young man, and then as he goes through the aging process, his prostate develops. And then it starts to produce PSA as part of the components of the

semen. Now, there is a certain amount of leakage of the PSA fluid into the bloodstream. It's not quote unquote supposed to leak into the bloodstream, but it can. And as the prostate gets bigger, so think about this concept of this underground sewer system, the New York City sewers, right? They're getting older, they're getting leaky here. And the bigger the prostate gets, and the prostate gets larger, as we get older, some of these pipes get leaky, and some of the PSA leaks into the blood. So it was discovered in the 80s that there's this prostate-specific protein that you can pick up in the semen and you can also see in the blood. And so it is not cancer specific. It's prostate-specific and it's actually a very good biomarker for prostate size, the bigger the prostate, the more leaky it is, so to speak, and the

leaky it is, the higher the numbers can go in the bloodstream. So there's two variables that can progress over time. The size itself, which you could talk about that independent size, so two 30-year-olds, one guy's got a five gram prostate, the other guy's got a hundred gram prostate just to make it extreme. You should see a difference. But also two guys with the same size prostate that are two decades apart, you might see a higher PSA in the older.

That's right. So, and if you do, for example, like we were always taught, you know, in, you know, residency, even though I wasn't a gyrologist, you still once in a while have to, you know, we still did a urology rotation. If I recall, you wouldn't check a PSA on a man right after doing a rectal exam on it, because in theory, that could artificially have raised the PSA, presumably by creating more of an insult and increasing that flow.

Pushing some of it into the blood, the bloodstream. So what can make the PSA rise besides just having, getting older and having a larger prostate? Well, if you get an infection in your prostate. So think about that like you got your city, you have your sewer network, if you get an infection in your prostate, so think about that like you got your city, you have your sewer network, and there's an earthquake. All the pipes are rattled a little bit, and they all are extra leaky, and that's what an infection is. It's not infections in the prostate are either all are none really. They're not focal. So the whole prostate

gets more leaky, and the PSA number can go way up. The other way to think about it is if you have a cancer and the analogy would be, there's a city block that has the pipes, you know, the sewer systems clogged. There's more backflow into the bloodstream and that's how it pick it up. That's not really how it happens, but that's a good way for patients to think about it. So what is a normal PSA? Well, a normal PSA is age adjusted. So a normal PSA for a 40-year-old is around 0.5 to 0.6 nanograms per ml. For a 50-year-old, normal meaning this is the median for all the population. For a 50-year-old, it's 1.

And so it kind of goes up stepwise by decade. So there are age adjustments that we do for the PSA number. Now what are PSA numbers that tell you you don't have a cancer? There's no PSA number that is 100% no cancer. But there is a proportional rise in cancer detection with rising PSA numbers. So originally the cutoff was set up a PSA of four. We do, you know, we think about things more based on the individual scenarios. So if you're a younger person, if your PSA is more than 2.5, that's usually considered to be abnormal and may want, you may need further workup. You don't need to buy up, you're right away these days, in my opinion, but you need further

workup. So it depends on the age of the patient and depends on how also their prostate size. Now, how many guys will go and when they get their PSA check, there's another thing that gets checked called the free PSA and then a number is reported, which is the percentage free, which is obviously that, you know, if their PSA is three and their free PSA is one, then the percent free is reported is 33%. What does that mean? These are different ways for urologists to try to fine-tune this prostate-specific antigen test to make it more a cancer-specific test. So again, PSA just goes up when you have an every man has it's not cancer-specific. So percent-free PSA was the first way that urologists began to look at, well, what's the chance

that a PSA of four is coming from a cancer versus a PSA of four coming from just benign overgrowth. So remember, there's a lot of factors in play. One would be if you had a man whose prostate volume was 80 grams, that's big, and his PSA was four, well, that's a low ratio. That's something called PSA density, how much PSA is made per gram of tissue. So you'd say, well, that guy, it's very low chance that he has a cancer. That guy would also have a high percent-free PSA. So percent-free PSA

is another way to just look at, well at how much of the PSA is produced from benign cells versus cancer cells. So if two guys have a PSA of four and one has a free of one, so he's 25% free and the other guy has a free of three, which is 75% free, what's the different physiologically in those situations? Well, there's less bound PSA in the lower percent free, and that's more often associated with prostate cancer. So, that's just a correlation. So, it's not like it means that... In other words, it's hard... You can't infer what? Because I would have assumed that the binding protein is in the periphery. It's in the plasma, right?

Yeah, it's bound up when it comes out of the epithelial cell. So it's just how it's processed. So PSA's process is not a full length protein when it's born. And so the other way that we now, so just for the listener, so we have absolute cutoffs for PSA for an older man, 2.5 and younger man,

but they're all really case specific in my opinion. Percent free PSA was the first way to say, let's try to fine tune what the PSA means. So a high percent free PSA is associated with a big prostate, less of a chance of prostate cancer. A low percent free PSA is associated with a higher likelihood that that PSA is produced from a gland with prostate cancer in it. The other variables that we use are PSA is produced from a gland with prostate cancer in it.

The other variables that we use are PSA density. So that's highly predictive of what's going on in the prostate. So easy threshold or cutoff for you, Peter, we talk on the phone about some of your patients. Percent free PSA density more than 0.1. It raises a little bit of a red flag, a PSA density of more than 0.15, that raises a red flag. So think about it. And a median prostate volume for a 60-year-old guy is 40 grams.

So 40-gram prostate, PSA less than four. It's probably, it's pretty safe. A PSA of six, six, that raises red flags. And you know the sum of your own patients that, okay, that guy probably has something going on. So that's how I think about it. Now, think about the 80 gram prostate with the PSA of four. Oh, you have these patients in your practice. They don't have cancer on average, right? A percent free PSA helps with that.

There are two other new tests that. Yeah, so you got me on to the 4k two years ago. and I really consider it a game changer for the guys like me who were in the peanut gallery. So I don't, you know, I make it my job to know as much as is knowable with the time that I have about every possible disease that could have flicked my patients, but that means I need to spend as much time thinking about colon cancer as I do coronary artery disease, as I do prostate cancer. So for me, the fork, hey, which again,

you didn't, I mean, you did me a great service. Not only did you get me interested in it, but you introduced me to Andrew at Memorial Sloan Kettering. I'm blanking on Andrew's last. Andrew Vickers. Vickers, yeah. Amazing guy. Yes.

And I mean, the guy couldn't have been more generous with this time. I mean, just gave me the schooling. It was really on this topic. So good. We put together a patient hand out on this thing, and he even edited it for us. I feel like I'm worried not enough patients understand that,

and I'm worried not enough primary care physicians understand the importance of the 4K test. Can you explain how that has changed the way we do things? So this test you're alluding to, and there's another test that performs equally well called the prostate health index or PHI test. These both leverage off this idea that prostate cancer cells make PSA differently

than benign prostate cells. And so the 4K score is the 4k chalichrine test. It takes PSA, percent-free PSA, intact PSA, and HK2. It takes those four prostate-specific proteins produced. And it has a calculator to really just discriminate between a cancerous cell and a benign cell. PHI uses the similar concept. It uses something called minus 2 pro PSA,

which is PSA for all the scientists out there plus two amino acids on the five prime side of it. So minus 2 pro PSA, right? And you measure those specific PSA base proteins in the blood. And the 4K score is great because Andrew Vickers and Hans Lillia developed it with this other great urologist, Peter Sgardino Memorial. And what they looked at was, well, what's the chance that this person is diagnosed with and has high

grade aggressive lethal prostate cancer? And it gives you a percentile chance. So when you get the 4K report, it's actually a really nice report. It'll say 2% chance, 20% chance, and so forth. And so now as you start using this in your practice, they now also give you the PSA. So you can see the PSA, and you can say, wait a second, this guy's PSA 6, but his 4K score is 2, it's safe. What I really like about it is, and so when we do our, usually with our patients in their second year, sometimes in the first year, but using their second year when we do our, usually with our patients in their second year, sometimes in the first year, but usually in their second year, we do a cancer screening program where we kind of walk them through every single cancer that you could possibly die of, and

then we go cancer by cancer, risk by risk, and it's a very lengthy process on the back end. For the patient, we simplified it, takes about 90 minutes to go through it. But for the males, when we come to this, I always view this as one of the better, I said I wish every cancer had a test like this because as we'll come back to, you know, pretty much every guy is going to die with prostate cancer. But fortunately, most men will not die from prostate cancer. That's right. But the job is to figure out when a guy has prostate cancer, is you alluded to earlier?

Is this the bad one? Yeah. Or is this the one that, if you muck around with it too much? And so what I guess, Vickers and his team have been able to do is figure out that there's now enough data that you can basically turn this into a binary test, you know, which, so the PSA would be a continuous variable. Right. And when you want to test the sensitivity and specificity of a continuous variable, you have to use something called

a receiver operating characteristic curve. And it becomes quite complicated because the question becomes what cut off? And as you alluded to, it's very difficult with PSA because it has to be age and volume adjusted. So now it's a three-dimensional receiver operating characteristic curve where you would have a different AUC, area under the

curve for each point in time and volume. I mean, that becomes almost inconceivable. And yet, the 4k has basically allowed us to say the following. If your 4k score is less than 7.5%, and I might butcher the numbers a little bit, but that's right. But if it's less than 0.5%, the probability that you will be alive, the probability that you will die of metastatic prostate cancer is 1.6% in the next 20 years. Yeah, it's almost the lifetime of the patient. And that's based on this data from Andrews partner, a co-developer, Hans Lillia, where they had this incredible serenade base from Malmo Sweden. So they could track it.

And then the reverse is, if you're greater than 7.5%, I think it's like 16 or 17% chance in 20 years. That's the binary cutoff is 7.5%. But it's a continuous variable. But above that, it's continuous. It's not like if you're above that, you know, it's a 50. So it varies based on the number. I hope you enjoyed today's quality.

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