Cheap blood test detects pancreatic cancer before it spreads

Noted medical researcher and oncologist Dr. Vinay Prasad appears to be one of those people. I don't know whether his statements are accurate but he seems pretty knowledgeable about the system.

https://www.sensible-med.com/p/cutting-nih-indirects-is-sens...

Yes - I mean in the private sector, hiring an employee is what, 1.4-1.6x salary cost? NIH indirects mirror that.

Fair enough. So what is the optimal percentage for indirects? Did the NIH previously have it too low, too high, or exactly right? Is there some way to quantify this?

"stupid people like trump and dont understand policy and are easily influenced. smart people(like me) like kamala and know whats best for everyone, how can we explain this to them"

hackernews is just reddit in slow motion

This is such surface level and frankly lazy dismissal of a stance or political view that a huge swath of people hold. It's like your "education" didn't really prepare you for the fact that other smart or educated people could come to different conclusions, so you use backwards logic to assign a label of uneducated to them just because they came to different conclusions. The arrogance of it is astonishing.

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You're doing great, keep it up!

> we now live in a world where vaccines, energy production and efficiency of use, climate science et al, are all "politicized".

Oh, you speak from my heart. I wish these were not partisan and weren't coded for allegiances. Some things we should just be able to agree on, much like water being wet.

Every time the Culture War escalates to cover another important topic I groan.

Not necessarily but that's the idea. Tumors will start shedding cells into the bloodstream as they start forming. These types of tests are able to identify tumor cells in a blood draw.

How generic these symptoms are! I always wonder if medical science has really attempted to study these diseases to understand their unique symptoms.

I lost my dad at age 62 last year to AML. His generic symptom was weakness.

Sure but the current state of affairs is clearly not optimal from an individual patients perspective. You notice this as you hit 40, 50 years old.

I know multiple "woops we don't screen often/early/proactively for that" cancer deaths in mid 30s to mid 50s.

I even know a few "wow good thing you had that CT scan for xyz, we just found some unrelated Stage 2 cancer elsewhere" people.

I know ZERO "oops false positive, we killed you with an invasive procedure" deaths. I know they happen, just clear to me its less often than the above.

Correct a lot of stuff can stop being screened for because of incidence of disease, how slowly it moves, expected remaining lifespan, and ability of elderly to endure whatever treatment they would receive anyway.

> In the case of pancreatic cancer, it is much more aggressive and you need to catch it early.

It's not clear that the cancers that you would find early with a more sensitive test are those more aggressive cancers.

The pancreatic cancers we find with our current detection (generally after becoming symptomatic) are typically quite aggressive. But are they all the cancers? Likewise, if the cancer is aggressive, it can grow quite a bit between screening intervals and not be found all that early.

(Part of why we think that "finding cancer early" is such a benefit is that because the smaller/earlier cancers we find are less aggressive than the cancers that we first find when they're huge and spread. There is definitely an effect from earlier detection but our estimate of it has been confused by this effect.)

As we've increased cancer screening, we've found that survival rates have gone up, as have survival times after detection... but unfortunately we've often also found that the screening doesn't always reduce the number of people dying of that cancer at a certain age. Instead, you find more cancers, and you find them earlier so more people live to 5 years, even if you've changed nothing. Cancer treatment has gotten better, but most of the benefits we have expected from better cancer screening have not materialized.

Finding pancreatic cancer early sounds good. And it may be able to reduce mortality from pancreatic cancer, but it's not a sure thing.

My grandfather (a doctor) always used to say this. There’s also an aggressive fast growing kind of prostate cancer, but treatment basically does nothing for survival rates (or at least that was the case decades ago when he was practicing.)

So his advice was, don’t look, don’t treat. Either you have the slow one and treatment is harmful, or you have the fast one and you’re going to die soon anyway.

You can just run test multiple times to eradicate this possibility or you can confirm it with another method.

Yah, I'm well familiar with the base rate fallacy and I still catch myself screwing it up. It's so unintuitive. I use mental math a lot to counter my intuition.

If sensitivity is high and the base rate is low, you can approximate it with .01 / (1-.91).

Or, mental math assuming 10,000 people is not unreasonable for your case (100 with disease, 90 true positives; 9900 * 9/100 false positives.. divide everything by 9 to make it easier, 10 true positives and 99 false positives, or 10/109 or say "9%".

You only get that probability if the test results are completely uncorrelated, chances are, they're not.

I'd assume the chances of getting a second false positive if you already got one are much higher.

No, I'm assuming there's a tradeoff between sensitivity (spotting cancers) and specificity (having your positive results actually be cancer).

ANOVA to pick variables and then reasonably selecting thresholds is a fine process that avoids overfit.

The big problem is, biology is messy and measuring lots of people to find correct thresholds is really expensive and time consuming. It's not really a technological problem, though technology has helped a little.

you will do surgery on some of the 105 people. Some of them might die from complications, infections, etc or at least have lasting damage. Since several of the 5 people will not be any better off with treatment it's entirely possible that the screening produces palpably worse outcome.

The earlier you screen, the worse this is, since the ratio of false positives vs true positives gets higher and higher, for example 1000 vs 5 or 10000 vs 5.

For example you might do surgery on people who wouldn’t benefit.

There's a ton of research and regulatory oversight in this area, and the choices made generally make sense. You can safely assume that the testing recommendations are 3-5 years behind the research, though.

The US Preventive Services Task Force (USPSTF) is the body doing that meta-analysis and writing recommendations. The recommendations are for general patients (high-risk patients should be identified and guided by their doctors), and are based on how much the screening/prevention will extend or improve patients' lives. The USPSTF explicitly does not consider monetary cost.

https://www.uspreventiveservicestaskforce.org/uspstf/recomme...

We do, it's not as if we aren't doing any testing. I've been getting a yearly prostatic antigen test for several years now.

The recommendations tend to take these into account, and then you and your doctor adjust.

Sometimes politics gets into it, like with the recent changes to breast cancer recommendations, but, overall, it works well for many people.

> Surely, though, we can do better as a society

We haven't even solved the most basic shit like shelter, food, education, &c for millions of people in the west, as a society we're faaaaaaaaar from universal yearly full health checkups. As an individual feel free to get private checks, they'll gladly take your money

GINA prohibits health insurance companies from denying coverage or setting premiums based on member genetics.

An update on that trial: https://www.bmj.com/content/386/bmj.q1706

It doesn't look great.

> If you're feeling like your doctor/PCP is a gatekeeper, get a new one, seriously.

The problem is that even if they open the gate upon approach, they are still keeping it. It’s not about being denied, it’s about being required to ask permission.

The existing downsides of a might-be-cancer hit on a test are real, for now - a statistically significant number of people with a breast cancer diagnosis end up killing themselves out of despair or doing radical surgery "to be sure", which detracts from the social benefit of mammograms. But there's no indication that they would persist if false positives were more common because proactive testing was more common. There would be a pipeline of followup testing and risk evaluation, which would be normalized by how common it was and how nonlethal diagnostic hits would become.

It would become "Oh, yeah, my cousin got a hit, but followup biopsy said it was a mutation that doesn't metastasize. Guess we'll see next week." rather than "My great-grandmother died of breast cancer, my mother died of breast cancer, my friend's aunt died of breast cancer, this feels like a death sentence", which is the information people who receive hits on their mammogram testing are acculturated with now.

He did say that you tune them to minimize false negatives.

I do find it interesting that in the early days of HIV testing even most people who got a "positive" result were in fact negative. The tests have since greatly improved and the number of people taking a test due to hysteria rather than likelihood of infection declined.

But I can imagine a world in which we get very many forms of liquid biopsies like this every year, and false positives become a thing we understand and are used to.

The emphasis there is on "further treatment". The test itself is broadly benign (except the general risks associated with phlebotomy and any risk of psychological harm).

The issue is that doctors often over-react to adverse results due to the risk of being sued if it did turn out to be a true positive.

I have two examples of this. One was during a routine blood test I had a liver enzyme flag up, which was then further investigated non-invasively with ultrasound and it was determined that I might either have moderately developed NAFLD (non-alcoholic fatty liver disease, I'm obese) or very early stage NASH (non-alcoholic steatohepatitis) associated fibrosis. The doctor wanted to perform a liver biopsy to confirm which is obviously an invasive procedure with a 1%-ish risk of complications.

My response was to ask how the treatment would differ between diagnoses, and he said in either case the treatment would be the same: lifestyle change. He agreed that from a risk perspective the biopsy was just inviting additional risk for no benefit, but that policy is to recommend the test and if I refuse it I'll need to sign an indemnification document saying I was refusing further diagnostics against medical advice. A few years go by, I've made efforts to improve my lifestyle, lost weight, and now my liver tests are all normal proving it was just NAFLD after all.

In another case, I had a suspicious finding in an eye test which (long story short) led to me getting two head CT scans which showed no problems. In hindsight, I think a double dose of brain radiation over a common minor finding with no other symptoms was a crazy over-reaction and I would have refused if I had all the facts, but it could have been a life threatening situation in some ridiculously tiny percentage of cases so it was all rush rush and I didn't have time to weigh it up.

Often the correct thing to do may be a combination of further non-invasive testing, repeating the test (possibly after a period of time), and "watchful waiting". Doctors often don't feel comfortable with the level of personal risk that could expose them to, and for good reason. That is the issue, not the test.

I feel like you're missing the point. Yes, false positives have risks. But if blood tests (or in the case of bowel cancer, fecal tests like cologuard) are effective, we can replace more invasive screening options with them. People have historically been encouraged to get colonoscopies once they reach a certain age because, for the general population, the risks of cancer are higher than the risks associated with a colonoscopy above the age of 50. Developing less invasive tests lets us lower that age, catching more cancers, while at the same time making screening safer for people already in the recommended screening window.

Also, pancreatic cancer, which is what the original article is about, has no alternate form of screening. Most people only find out they have it once it's already symptomatic, which is usually stage 3 or 4

> The medical world weighs these things against each other and determines when the data shows that the risk of mortality from testing is smaller than the risk of cancer.

Let the patient weigh the odds. Especially when they can afford retesting or may be otherwise in good health or whatever. Plus the test’s algorithms can be tuned to provide more or less false positives.

the obvious answer is additional testing to reduce the likelihood of a false positive -- if additional tests are invasive those tests can be weighed on the balance of risk just the same. i think the real problem is cost, we cant afford/manage to do that correctly currently, which is exactly what improved non invasive tests could enable and disrupt this reactionary approach forever

No, the worst case is death. Overdiagnosis of cancer leads to overtreatment, which has a risk of harm.

Traditionally, tests have been metered that way because of costs (expensive reagents, preparation, processing) or side effects (radiation from scans).

But the actual relevant equation is {cost of testing} vs {cost of delayed treatment}

If the cost of testing, in economic and health senses, decreases while the cost of delayed treatment holds constant, a different mass deployment optimal point is created.

Thankfully broader proactive testing is also in insurance companies' financial interests, given the high costs of late stage cancer treatment.

One way to test lots of patients where a) there's a low probability that an individual patient will have the disease and b) the test is expensive is to first mix some of the blood of each of N patients and do one test on the mix. If the batch tests negative then all patients are negative and you've only paid for one test. If the batch tests positive then you have to repeat the test on the remaining blood of each of the N patients to determine which were positive. Thus, with a high probability you only pay for 1 test, and with a low probability you have to pay for N+1 tests. The value of N is easily computed to minimize the overall cost, given the cost of each test and the percentage of patients that have the disease.

I think these days they do recommend screening all children for cholesterol.

Nearly everyone will reach 30 in their life, so it is safe to say we give them to everyone. It isn't a one and done test, cancer can form at any time in your life. To be useful we need to give this to everyone over 30 (40, 50....?) , on a regular schedule (yearly?). The article doesn't specify those details (or at least not before I hit the sign in wall)

This is it, I am not sure how people can be so dismissive about the risks of over diagnosis.

However, usually there are studies done to carefully weigh the risks and benefits of testing likes this. I would expect tests like these to become the norm for screening at risk populations at some point (usually people beyond a certain age or people with family history).

If we don't detect more people early and try to cure them, it will never be solved. The more people that get detected early, the better chance everyone has of surviving, especially those in the future.

In the US, asymptomatic people 50+ are routinely screened for colon cancer with a much more expensive and invasive process. A cheap blood test for another major killer seems pretty reasonable to add in.

There's a long list of stuff people are supposed to be screened for. Many people die of stuff that has high survival rates when caught early.

Pap tests, mammograms, prostate exams, are other examples for cancer.

Measuring your blood pressure is an example of proactive screening.

I assume we will start screening for things like cancer when the test will be as simple / cheap as measuring your blood pressure.

So you are arguing we should just let people die?

This is a cancer that is typically detected only after it advances far enough that you will be dead in 6 months (not treatment possible). If we could detect it 2 years sooner it would be treatable and most people could life for many more years. Sure the total cost of a positive will be much higher - between whatever tests to verify it isn't a false positive, and all the treatment it will be a lot more money. However by spending that money many people will live a lot longer.

Maybe you don't like any old people, but I often wish I could show my dad my latest project. This test could have saved his life if we had it 15 years ago.

That assumes that what causes the false positive is some kind of analytical noise in the test. The bigger concern is biological noise that would persist if you tested the patient again.

It might still be useful to know you have weird protease activity that isn’t cancer derived, but the more of these tests we do, the more likely it is that for every person, there’ll be at least one non-cancer oddity that looks like cancer signal for at least some test.