#170 - AMA #25: Navigating the complexities and nuances of cancer screening

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Hey, everyone, welcome to this week's episode of the Drive. Today is an AMA with Bob Kaplan, and in this episode, we go super deep on cancer screening. We've had so many questions about this, and we kind of lumped them all into one episode. So we get into kind of the what you need to understand cancer screening, sensitivity, specificity, positive, negative, predictive value, all those things, and then kind of go through the different modalities, I. E. How you would actually go about doing these screens and how you can improve their predictive value by stacking them on top of each other. So hopefully you enjoy this one. And check it out. This is probably a really good one to check out on video because we use a lot of visuals, including a spreadsheet that you can manipulate to better understand the concepts. So if you're a subscriber and you want to watch the full video, those podcasts, remember, you'll want to see it on the Show Notes page. And if you're not a subscriber, you can at least watch the first part of this video on. On our YouTube page. So without further delay, please enjoy AMA number 25. Hey, Bob, that's a lot of books behind you, man. Have you read all of them or most of them?

Thanks for noticing, Peter. I'm a voracious reader. Sometimes my appetite is too big, I have to admit. I haven't read all of them. Maybe 90%, I think at this point.

It's impressive. Everything, the classics, literature, science.

Mostly the classics. You can probably tell by the book binding on some of those. Yeah. Hard to get them out of the shelf, to be honest, to pull those things out. They're in there so tight.

Yeah, and it's good, too. Your kids can do little projects, flattening leaves and stuff like that. Yes, we've got more of those going.

It's fun for the whole family.

All right, well, what do we have on the docket today for AMA number 20? Something? 25.

25. In a similar vein as some of the previous AMAs, I consolidated a bunch of questions around a particular topic, and this One is cancer screening. We've gotten a bunch of different questions related to cancer and cancer screening. So you've got. I'll give you a flavor some of the questions that we've received. How do you think about cancer screening? Why and or when should I be screened? Which tests are worth getting? What do you think of liquid biopsies? How do you interpret sensitivity and specificity of tests? What do those actually mean? What are some screening tools for cancer you use in your practice? Was another one. I don't know if this was a question from someone, but I found this very interesting. And this question is, can you discuss how you categorize cancers and how you screen for each? I remember you told me this too, and it was pretty interesting. I don't know if everybody would suspect this answer, but cancers outside the body versus cancers inside the body. So we'll get into that a little bit. But I think it probably makes sense to start off with sort of in general. I know you're a strategy person. I know you love tactics, too.

Now, just to be clear, Bob, do we have three or four hours set aside for this podcast?

Hopefully it's the latter. Yeah, I think this could be a long one.

Where would you like to begin?

I think we should begin from the top. The first question was, how do you think about cancer screening?

I guess putting this in the context of what we're interested in clinically probably sounds repetitive, but longevity has these two components and they're not independent, but sometimes it's helpful to think about them in isolation. Lifespan, healthspan. How do you live longer and then how do you live better? In many ways, cancer versus the other major chronic diseases that rob a person of lifespan, namely the atherosclerotic diseases and the diseases of dementia and neurocognitive decline. The latter two tend to go more hand in hand with the reduction in health span. In other words, by definition, when a person has Alzheimer's disease, their quality of life, that is their cognition, is also deteriorating, so they're experiencing both the slide and quality of life and eventually length of life. And similarly in people that have advanced atherosclerosis. While of course it's true that people die suddenly of heart attacks who are otherwise totally healthy, a lot of times the reduction in the ability to carry out activities of daily living kind of moves more hand in hand with that, I would say that's a little less the case with cancer. Obviously, cancer is still a disease whose primary risk factor is age. So age is the greatest risk factor for cancer. Just as it is for the other two diseases. But it's also in some ways a little bit easier to think of cancer in isolation from the health span stuff, the decline in physical and mental health, mental and emotional state. So if you're trying to imagine a world in which you can live longer, as we've discussed many times previously, that means living in a world where we delay the onset of chronic disease and or have better tools to live longer with chronic disease. But you know that I much favor the former option because we've basically spent most of the history of modern medicine working on the latter option with very, very limited success. Let's now pause it for a moment. That one of the pillars of longevity is minimizing mortality from cancer. So where does screening fit into this? Well, screening is one of three pieces that you would envision, right? The first piece would be how do you prevent cancer? The second thing would be how do you screen for cancer and detect it early? And I'll explain why I think that's necessary. And the third is how do you treat it when you have it? We can talk a lot about the former. How do you prevent cancer? We've had many podcasts and we have many podcasts coming up where we're going to get into the treatments of cancer. But I want to focus this one on the prevention piece. So why do I believe that? Well, this is a controversial topic. I want to say first. So not all people believe that screening matters, But I think the simplest explanation for why screening matters is the evidence that suggests that a cancer that is caught earlier is easier to treat than a cancer that is caught later. In other words, if you catch a breast cancer or a colon cancer, when there are tens of millions or hundreds of millions of cancer cells, your odds of treating that successfully are better than if you catch the same cancer years later, when there are billions of cells. And the evidence for that basically comes from examining how patients respond to the exact same drugs in the adjuvant setting versus in the metastatic setting. What does that mean? So the adjuvant setting is when a drug is given to a patient who has no visible cancer. So these are patients that may have had the visible cancer removed. You believe that they have microscopic disease that remains, and you give them a drug like herceptin for a HER2 neu positive breast cancer. And if you compare the outcomes of those patients to the outcomes of patients who were given the exact same drug for the exact same phenotype and genotype of the cancer, but in the metastatic setting, there's no comparison in the outcomes. And one explanation for that may be that the more mature cancers, the ones that have been around longer, have developed more mutations, they are more difficult to treat. So it is therefore my belief that the more we can do to screen for cancer and catch it earlier, the better we will be. But we do pay a price for that. We pay a financial price for that. In other words, it costs money to screen early and we pay potentially an emotional price from that. Because as we'll get to, and you alluded to, we have to now get into false positives and false negatives, but at a high level. Bob, that's how I think about this topic around cancer screening.

Yeah, it's telling too. If you look at statistics on five year survival, so what are the odds of you surviving a cancer? And then if you look at specific cancers like breast cancer, you're talking about you catch it early and it's a local cancer, it hasn't metastasized. And the statistics on that is the five year survival rates are 99%. And then you go to a, like a distant cancer, so a metastatic breast cancer and it's closer to about 25% in terms of the five year survival. Also, what you alluded to as well, the false positives, false negatives, I said I alluded to that. So that gets into sensitivity, specificity, and I didn't mention this, but positive predictive value, negative predictive value. And I think it probably would be helpful to go into that. And I think pictures are probably worth a thousand words in this case in terms of looking at how good a screening tool is and determining that stuff, sensitivity, specificity, et cetera.

Wanna just start explaining those things?

Sure.

We've got some slides that we use with our patients, so go ahead and pull these up and we'll walk through that. Because I think if you want to take ownership over your own understanding of cancer screening, you'll definitely wanna get to a point where you're really facile with these terms.

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