Early Cancer detection by Peter Attia (ENG)

#cancer #labtest #learnMedicine

Table of Contents:

A - Intro - Preventive Medicine Approach (Medicine 2.0 vs Medicine 3.0)

In our current times (2023), humans primarily succumb to "slow killers", also known as chronic diseases. Medicine has evolved from its origins to efficiently address immediate threats from "fast killers", such as infections or trauma. However, nowadays, we lack an effective approach to proactively treat chronic conditions before they advance into incurable stages.

For example, the approach to treat "fast killers" is known as Medicine 2.0 and it is not well suited for chronic disease

That is why we need a new approach based on prevention, known as Medicine 3.0

B - The Four Horsemen of Death (the slow killers)

Those "slow killers" are the 4 four horsmen of death:

Each of the horsemen has a slightly different "Playbook" to go down with Medicine 3.

B.1 - Types of Cardiovascular and Cerebrovascular Disease

Cardiovascular disease is the easiest of the "four horsemen of death", because nowadays we have a lot of understanding of what causes it and have many tools that can help us prevent it (pharmacologically and non-pharmacologically).

B.2 - Types of Neurodegenerative Disease

With Alzheimer's disease, we actually have quite a strong sense of what the drivers are. Some of them are not modifiable (they are 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.

B.3 - Types of Cancer

Cancers are classified based on the organ or type of cell in which they originate:

• Carcinomas are cancers that occur on the skin or tissues that line internal organs.
• Sarcomas are cancers that occur in the bone, cartilage, fat, muscle, blood vessels, or other connective or supportive tissue.
• Leukemias are cancers that occur in the cells of the blood and bone marrow.
• Lymphomas are cancers that occur in the cells of the immune system and typically appear within the lymphatic system.
• Central nervous system cancers are cancers that occur in the cells of the brain and spinal cord.

• we know that smoking dramatically increases the risk of cancer
• we know that the second leading environmental or modifiable risk factor for cancer is obesity (specifically hyperinsulinemia and inflammation)

but cancer has shown us it is more complicated than that.

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, this "bad luck", can push you to acquire enough mutations to drive a cancer.

And the reality of it is that minimizing that risk for cancer can still be ineffective in preventing these mutations to happen. This current state on cancer understanding,, this "bad luck", what it does is it calls to our attention another tool that is essential in our fight against cancer and that is the tool of very early and aggressive cancer screening.

D - Why must we consider Cancer Screening?

Cancer Screening is a highly controversial topic, but the rationale is unambiguously straightforward based on the following:

• there is no example 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 becomes)

I believe the easiest way to understand this is that when you have lots of cancer cells, they are different from each other (you have an heterogeneous population of cancer cells), and they change in different ways (they have different mutations). As these changes increase, there's a bigger chance that the cancer can survive treatment. This means that when you give a strong treatment like chemotherapy, the more changes there are, the more likely it is that some cancer cells will escape the treatment. These escaping cells can then grow into a new group of cancer cells that the treatment can't stop.

D.1 - Stage 3 vs Metastatic Colon Cancer Example - The Importance of Cancer Screening

For example, just to look at colon cancer or breast cancer for which we have so much data. 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 (60-70%)

And, 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.

We can see similar situations with other cancers like breast cancer. So, even if we make efforts to lower our chances of getting cancer by staying active, eating well, sleeping enough, and avoiding things like insulin resistance and smoking, we're all still vulnerable in the end. That's why I believe it's really important for us to think about how early screening can help us have a fighting chance if we do end up having cancer.

E - Cancer treatments throughout time (Immunotherapy)

Another thing shows the importance of early and aggressive screening is another fact, which is that treatments over the last 50 years for cancer haven't really come along that far. For the most part, our overall survival rate from cancers is not much better than it was several decades ago.

For example, for Metastatic Solid Organ Cancers like Epithelial Tumors, Solid Organ Tumors, it's been an improvement in overall survival of only 5% in 50 years (so that does not include leukemias and lymphomas, especially Hodgkin's lymphoma, where we've had remarkable success of treatment).

Now we're starting to see those numbers get better and better overall 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 is 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.

In the beginning, immunotherapy was mainly used to treat melanoma and a type of kidney cancer known as renal cell carcinoma, but back then, we were only beginning to understand how powerful checkpoint inhibitors could be. We initially applied them to melanoma, and now we've come to realize that these checkpoint inhibitors can actually be effective against many different types of tumors, as long as those tumors have a specific kind 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 that 80% of solid organ cancers have cancer antigens that are recognized by the immune system.

Summary - how checkpoint inhibitors work:

Learn more here:

• Cancer Immune Checkpoint Inhibitors

F - Cancer screening methods (the 2 main categories of cancer)

I want to talk about each specific type of cancer screening that that we have available, it's helpful to organize the two big buckets of cancer screening into:

• cancers that happen inside the body (less visible)
• and Cancers that happen outside the body (more visible)

The easiest way to think about it is,

• can the air (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,
• also, everything from your mouth to your anus is also technically outside your body, so it is also a yes
• this does not apply to lung cancer (cancer doesn't occur in the air sac, so it doesn't really apply to lung cancer)

now the significance of this is primarily that you can look directly at these cancers (with your on eyes or with cameras)

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 are prostate cancer and breast cancer
• number three is colon cancer

So, if colon cancer is visible now a days, why is it the third leading cause of cancer death?

F.1 - Colon Cancer screening specifics

Nowadays you can look directly at the colon as it transitions from being perfectly normal to developing something called a Polyp, which is a small clump of cells that forms on the lining of the colon.

and that transition is a necessary first step towards the development of colon cancer.

Most polyps do not become colon cancer, but every colon cancer comes from a polyp, this is a very important step. It means the development of a polyp is a necessary, but not sufficient step for the development of cancer.

F.1.1 - The Colonoscopy

And we have a tool, the colonoscopy that allows us to look directly at the colon and identify any and all polyps and remove them, and if you think about it, really nobody should die of colon cancer if we accept screening at a high enough rate, it shouldn't be the third leading causes of cancer death.

1. When to Start Screening:

What age is recommended to do their first colonoscopy? and that's assuming the patient is willing to pay out of pocket if needed.

• It depends on number of things, it certainly depends on:
  • family history and other personal risk factors such as,
    • 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.
  

2. How to determine Screening Frequency:

and then the frequency, we typically recommend screening at 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, this depends on the quality of the bowel prep

bowel preps have become much much easier, nowadays you 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

The most recent and comfortable bowel prep nowadays is SUTAB, it is only a bunch of pills.

but when the endoscopist is doing the colonoscopy, he or she basically makes a designation with a rating system called the Boston bowel prep scale, but it's basically how well was the endoscopist able to visualize the colon

So we're really looking for two things:

• to wait three years to do it again, we want no polyps
• and we want a perfect visualization of the colon

if those conditions aren't met then we now have to decide on when the next colonoscopy should be.

3. Screening Risks:

The colonoscopy and the bowel prep itself, is not really a risk at all for adults in their 40s, just an inconvenience. But for older people, there is absolutely risks to keep in mind like, the risk of electrolyte abnormals and dehydration, the sedation itself is a risk.

All of these risks are small, but none of them are zero.

So you have risks that are associated with not breathing (from sedation or dehydration) 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.

Metrics to Consider before a Colonoscopy:

Always ask your endoscopist

• "what's your perforation rate?"

It's nice to know 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:

• an outpatient elective colonoscopy, what is your bleeding/perforation rate?

Also ask

• "what is your cecal intubation rate?" So, that mean how often are you getting into the "cecum".
  

And

• "what is your typical endoscopy time?" so what is the total time of scope

There are established metrics on which values are considered ideal for this purpose

F.1.2 - Upper endoscopy (recommendation)

Doctors generally recommend their patients undergo an upper endoscopy, so 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.

Therefore given that it poses no additional risk to the patient, given that they've all the risk condensed into the colonoscopy. Doctors generally recommend doing that as well.

And surprisingly, doctors do at times find pre-cancerous lesions in the esophagus in people who maybe only report 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.

F.1.3 - Other screening methods (stool-based tests)

A nice thing to do on the off years of colonoscopy, is to do a stool-based test.

So you can do:

• A Fecal Occult blood test or FOBT (less effective method)

• A Fecal immunochemical test or FIT (more effective)

A stool test is looking for tumor DNA , so in the off years you're at least looking for a signal of cancer.

Again, that's nowhere near as effective as a colonoscopy but of course it poses no risk.

Doing these test is better than not doing anything in the off years, and if the stool test is positive then you would go straight to a colonoscopy.

Remember that colon cancer can develop in as little as six months in some patients. So regular screening is the optimal strategy. Specially on those off years while we wait for our next colonoscopy.

F.2 - Breast Cancer screening specifics

Let's talk about breast cancer and again maybe just start with your your approach to to breast cancer screening if if there's um you know a particular age I know every patient's different but um if there's not a strong family history of breast cancer is it a particular age that you recommend you know starting screening for breast

(TO DO)

F.3 - Prostate Cancer screening specifics

F.4 - Lung Cancer screening specifics

Extra Episode - What blood tests can (and cannot) tell you about Cancer

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1. What drives cancer?

Cancer is both a genetic and metabolic disease likely, so by definition cancer cells have mutated and they sort of have this trait that is common to all cancers which is "dysregulated cell growth" so it just means that cells that grow without responding to normal cell cycle signaling.

2. Cancer and the immune system

We know that obviously there's a strong immune component to cancer because our immune system is almost always keeping cancer at check and keeping it at bay, so at some point when our immune system starts to lose that battle that's when cancer starts to win.

3. Environmental causes of cancer (smoking and obesity)

We also know that there's a very strong metabolic component to cancer, for example we know that after smoking, the next leading sort of "environmental toxin" for predisposition to cancer is obesity, which includes hyperinsulinemia and and other metabolic environments that heavily impact metabolic health.

So there's no question that cancer is a disease that's heavily impacted by:

• the underlying metabolic health of the individual
• the immune function of the individual
• the ability to acquire mutations and repair them, etc (Somatic Mutations)

Unfortunately, we don't have much we can deduce from a standard blood test when it comes to everything I just described (outside of the metabolic part).

So everything that we learned about the metabolism of an individual to help us understand their risk of heart disease, we can apply right here as well so, glucose and insulin primarily being the two biggest ones (by far insulin because it is a growth factor, it's a very potent and anabolic growth factor, for example, consider insulin biding proteins like IGF-1 (Insulin-like Growth Factor 1), all of these things factor into cancer and of course glucose as well glucose being the preferred fuel of cancer).

4. Is Cancer a Genetic Inherited Disease? Not really...

One thing patients say when they had a genetic test, like a 23andMe test, they ask: "doesn't that tell me about my risk of cancer given that it's a genetic disease?" and the answer is basically "no", it does not.

The genetic tests that people get when they do you know genetic sequencing are what are called Germline genes so these are the genes that you inherited.

Most cancers do not arise from inherited genes, it's on the order of 5% of cancers that come from inherited forms of cance. The majority of them, at least 95%, result from somatic mutations. So mutations that occur to your genes and they're not that necessarily the genes you pass on.

5. Lack of info about cancer from blood tests

So I close that chapter by saying: we don't have any real sense of if you have cancer from a blood test.

There are only some very inaccurate biomarkers that are never really appropriate for screening CA-125 or CEA those should never be used for screening, they're absolutely grotesque.

We do use things like PSA test and 4Kscore Test and we'll talk about those probably another time, when we get into a whole section on cancer screening. But the long and short of it is there's very little in a blood test it's going to tell you about cancer. What we instead rely on a blood test to do, is at least tell us what your metabolic environment is and how much that's predisposing you to cancer.

X- List of cancers screening methods

• Colonoscopy

• Upper endoscopy

• Fecal Occult blood test (FOBT) (stool-based test.)

• Fecal immunochemical test (FIT) (stool-based test.)

• IGF-1 (Insulin-like Growth Factor 1) test

• CA-125 (not recommend)

• CEA (not recommend)

• PSA test

• 4Kscore Test

• Galleri Test (age restricted)

Y- List of cancers mentioned

• Hodgkin lymphoma
• colon cancer
• breast cancer
• leukemia
• melanoma
• renal cell carcinoma (kidney cancer)
• lung cancer,
• prostate cancer
• breast cancer
• mouth/esophagus/stomach/duodenum cancer