Proteins in blood could provide early cancer warning 'by more than seven years'
theguardian.com
theguardian.com
The video makes the case that the early detection of cancers isn't always a good thing. See 6:30 and 7:00 for specific references to scientific studies. Some cancers (thyroid and skin) can be detected at a much higher rate, but the associated mortality remains constant (we are detecting benign cancers).
To be clear: obviously this is dependent on the cancer. Really my point is that we need studies that show that the screening improves outcomes.
Now, this is what they say... I have tried to find the actual literature they use to motivate their protocols, and apart from occasionally, have not been able to find that evidence. I'd love to have a resource that demonstrates these sorts of things.
Heavy agreement on your last part - if there is substantial evidence to back this up I would like to see it.
As it stands I personally prefer the idea of constant mass testing in order that we learn as much as possible as quickly as possible, including improving the tests from the resulting feedback loop.
I really wish there was more transparency, because test aversion is exactly the same protocol you'd invent if you were trying to save money. I want to be able to see which of the two we're dealing with.
Medical experts here have very little say in how things are run. It's all bankers and bureaucrats.
I've worked for a hospital and I've never been able to find anything approaching a complete balance sheet. Financing it utterly opaque, but I'd love to have something solid before I accuse anyone.
The surgeons use to run the hospital. In contrast with mba's they knew things. I don't know what the difference is precisely but I hear the ziekenfonds use to have people to divide money over treatments (set prices) without their salary depending on their choices.
I don't know about the scale but longer ago we would just build hospital buildings and house a workforce of nuns nearby who had their own garden. Now we some how cant afford to put down a building and with realestate prices on the rise the salaries need to follow. We might not like the factory village concept but if you have to be on call all of the time it seems fkn convenient to me. Cut the salary and give the employees a house, seems a great perk.
Employee shortage is also costing a fortune.
We've created ambitious labor protection laws then we created a loop hole where all you have to do is pay 190% of the salary to a job agencies (uitzendbureu) and no laws apply, anything goes. If you don't like it you can go home. This didn't need to cost 90% of the salary. Unless our labor taxes are now that complicated(?) but that doesn't work as an excuse either.
Our taxes not paying for education doesn't mean we don't have to pay for it eventually (+interest)
I read they are also lacking the money to streamline the processes.
There's just an enormous number of tailwinds pushing overdetection and overtreatment. The sum of that is what's important, which is that when you test earlier, you often objectively end up with more death and suffering. Which is what a state-run national healthcare systems needs to look at, they can't get lost in the trees. You pick an optimum age for testing that shifts the balance to less suffering and death (and costs), and you look for specific exceptions (genetic, lifestyle, comorbidities) and test just those people early.
Could there be a way in which all testing would help instead of hurt? Yes, but it's political and psychological and not likely to ever happen. You'd have to (as a patient) trust probability in general, and additionally you'd have to trust the probabilities that they're handing you haven't been distorted by the self-interest of others. Not likely for the foreseeable future; maybe 1000 years from now.
If you want to do the study, all you have to do is compare the number of deaths from a thing when people are tested early to the number of deaths when people are tested late. Or just look for other people who have done them. If early testing obviously saved lives, the people who sell testing would tout them everywhere. Instead, they're stuck trying to look for angles to argue that lessening death and suffering isn't the biggest consideration. They recently did this to push breast cancer screening earlier again, by arguing that if you specifically look at black American women, they benefit from early cancer screening. So overall, breast cancer deaths go up, but that's just your privilege talking. Woke conglomerates. Ignore that black people have a unique, neglected, discriminated against, and poverty-ridden situation in the US; in fact, it might even be racist to point that out (in backwards land.)
Of course, you definitely don't have to do the studies, plenty have been done. Anybody saying that they've looked and haven't found them has not looked or has seen them and is not telling the truth. Both positive and negative, about every test. The studies that support earlier and more testing are press released and marketed, though, while the others can be suppressed or simply ignored, unless some public health system or insurance company champions them, and of course they would.
However, the converse is also true: we don't actually know which protocols are there because they're social, and which are there to benefit the insurers. Both could motivate cost cutting.
I want to see the difference. I want whatever the full story is laid out in front of me.
On a population based level it makes perfect sense to not do things even if it could save lives.
This is exactly what NICE does in the UK. If it costs more than 30,000 GBP to give one person one more full quality year of life, then it’s not worth it.
2) These are averages per treatment or protocol and in most areas the NHS spends less than the threshold by simply delivering based on clinical assessment of benefits, and so the threshold is limiting treatment mainly on the fringes where you find a few very expensive treatments with marginal benefits with no cheaper alternative.
In practice NICEs threshold is what any insurer would do: You know how much money there is in the system and try to maximise health output with what is available to you.
This is what makes Americans getting upset their insurance rejects coverage for medicines so ironic.
Single payer systems do the exact same thing. The difference is in the UK is the option is just isn’t brought up in the first place because the doctor already knows it’s not paid for.
The average cost of private health insurance in the UK is ~$114/month.
The US insurance pays for everything. UK insurance layers on top of the public system.
Plus UK insurance excludes pre-existing conditions.
In the US you can get diagnosed with cancer and then buy insurance to pay for it.
Having lived a decade in NL, my impression was that keeping costs down is the top priority. Unless you have a serious chronic condition or were in an accident, good luck getting somebody to take a look at you.
(irl, after a while you learn to push, exaggerate symptoms etc. or just go back home to get tests and treatment).
For the benign ones, that's going to hurt the person's body quite a bit
Should also point out that tests will negatively affect your life seriously either way, especially if these benign cancers are common. Think of the time spent going to/from the doctor, the incredible stress (am I dying?), the tests itself: it is damaging the person's life. Detection is good, false positives are unacceptable though.
e.g.,
My two friends who got early screening had a few false positives, and one true positive treated early. One later died of heart attack and one lived long enough to get dementia.
My two friends who didn't get early screening, one died of heart attack and one died of cancer that could have been caught. Both died earlier than two above.
Sadly, at this point, you want to die of cancer, but you want to do it when you're 85. It beats a sudden heart attack and it beats dementia. You just want to prolong the outcome.
I don't know any "did early detection which lead to unnecessary chemo" stories..
I know people who died due to the lack of early detection.
I also know people who survived due to accidental pre-symptomatic detection because of unrelated ER scans where they'd have been in stage 4 before having any symptoms.
So more screenings for more types of cancer are absolutely needed. It's more treatable early, and you will have better outcomes.
Patients might worry about lab results is not a good reason not to have early detection. Patients can self select if they are so sensitive.
Nobody would give chemo if the tumor is known to benign, after all.
An unnecessary chemo will be one where they couldn't tell, and the chemo ensures they wont tell.
The only way you'll know is from aggregate mortality statistics not budging.
The other aspect is that even if a tumour isn't, earlier detection is often not reducing mortality any more once you get to a decent baseline.
The evidence often does not support early screening in general. Early screening for specific subsets of the population have better results, but are also not unambiguously helpful.
I have seen a few people get benefits from a cancer scare: a refocus onto what matters in their lives. Agree: I would guess most people just get costs. Of my middle-aged friends with health scares only a few addressed the underlying cause (and even fewer are proactively avoiding health issues).
once the train leaves the station theres a lot of steam to go in 1 direction only
If the cancer is very fast growing, it could be too fast for treatment to help at all. Even if treatment helps there likely not a very long period of time before you develop symptoms that would have lead to treatment regardless.
If it is very slow growing, you might outlive the cancer and it doesn’t require treatment. It is effectively but not actually a benign tumor.
You also have to deal with false negative and positives, that could be an order of magnitude higher than the Goldilocks true postives that earlier detection actually made a difference. It’s easy to see how population results will not show much of a benefit.
The USPSTF references a lot of meta-analyses dealing with screening outcomes. They make decisions by whether a specific screening practice decreases mortality rates. They explicitly don't even include the financial cost of a screening practice.
I assume you're referring to mammograms. You do get exposed to a significant amount of ionizing radiation in mammography, about 0.4mSv, about 40% of the EPA's annual radiation limit for a member of the public.
That's one of the very good reasons why guidance is women wait until age 45 to get annual screenings and switch to biennial at 55.
At that point the rewards outweigh the risks.
For a test with high enough specificity and sensitivity for early detection, it's likely that it would be quickly adopted, and then studied to show that it actually improves outcomes without undue cost (not merely dollar cost but also health cost) to people in terms of treatment and its side effects.
It's interesting because they explicitly talk about follow up testing (@2:10) which is to say that multiple methods are used if the MRI indicates a problem. So yes, the initial MRI may produce a misdiagnosis and that is a defect of the test. But the commentary in the video obviously suggests that additional testing for early detection is done. That's partly a problem as you pointed out, but then it clearly also indicates the scope of the conversation is more broad.
You've misunderstood the comment's point, which is "just because prospective full-body MRI is bad doesn't mean all diagnostics are".
I'm not saying anything that the studies aren't saying. For some kinds of cancers and for some kinds of screening methods, screening can result in overdiagnosis.
There's no doubt that some diagnostic tests - like getting a full-body MRI as a precaution - may do more harm than good. Your apparent mistake is thinking that means all diagnostic tests probaby do.
We'll have to figure out which one this is; it's a start of that process. We've demonstrated we can do it; now we have to figure out if we can distinguish between "big bad scary" cancer and "whatever it won't kill you" cancer.
However, early detection is responsible for greatly improving outcomes in many specific cancers. Full body MRI is not the test to achieve that. GRAIL's gallery test might be one to do it for many classes of cancer, but that still remains to be fully seen.
The general of idea of early detection is still an extremely promising one for most types of cancer, and in particular for some of the deadliest, like ovarian and pancreatic cancer.
I just find it fundamentally hard to believe that having more data is a bad thing. What we choose to do with that data is a different story, and the actual source of these bad outcomes.
Are most people?
You could have a scan 3 months later and if there is no progression the doctor schedule a scan 6 months later and then 12 months... If there is a progression he schedule an appointmentwith an oncologist.
E.g. how many of them end up leading to unnecessary biopsies, or scans that are themselves introducing a risk?
For any condition there will be a threshold where too much screening becomes harmful because you're doing so many unnecessary tests that rare errors / accidents come to dominate the benefits.
The question isn't if there's a threshold where more scans do more harm than good, but where it is.
For some things, increased screening will be unambiguously good. For some it takes work to figure it out.
Enhanced imaging and blood tests alone didn't do this: their intuition based on progression and behaviour of the system as a whole did.
Treat the person, have a longterm relationship with your health provider.
That kind of data, the costs, we have tons of. That’s why pretty much every medical association regardless of culture has limits on recommended screenings.
There needs to be a net positive action on a subset of the cases to outweigh the costs of gathering and sharing the data.
Having more consistency between doctors would already be a change needed to actually use data. You will find it matters more than you'd like. We can't all have the best doctors, but we could use data to level the outcomes.
That said, I think engineers seem to believe other careers should use logic in a straightforward fashion, but they are more complicated.
For example, lawyers cannot use logic in the same way, because the court can almost arbitrarily say some facts must be ignored.
In the same way, medicine has the hippocratic oath. It is "do no harm". It is not "find the cause" or "cure the patient".
It seems doctors have made their peace with this and are aligned with it, since the overwhelming majority 88% have do-not-resuscitate orders for themselves.
My wife ultimately lost her life to metastatic melanoma, which was believed to be in remission. Had there been a way to detect the proteins associated with the mets that developed ahead of symptoms, the odds are she we be alive and thriving.
In other scenarios, say most prostate cancers, early knowledge has low or negative benefits.
I would be wary of a study conflating screening with outcomes — that is unnecessarily coupling too many factors. [1]
The screening isn’t an intervention, so why would it make sense to study its effects on an outcome? Those effects are indirect, mediated by the causal factors of the choice of treatment.
Am I missing something?
Perhaps you are looking for psychological effects of getting an early test?
[1] Treatment outcomes depend on the current state of technology and the practice of medicine.
If a screening procedure leads only to interventions that would be made in time anyway, it doesn't provide a benefit.
If it leads to extra interventions and no drop in mortality, it may be a net negative.
E.g irradiate enough people to find more cancers and not improve outcomes, and some of your screening may lead to cancers.
It really gave me a new perspective on diagnostic testing.
Sure maybe the first few years the outcomes may not change, but what about 20 years from now, when a generation of scientists can detect cancer years earlier?
The defeatist attitude of "well it doesn't fix anything right now" is really strange. Once we have reliable detection, it means we can find reliable treatment as well.
Sure .. but ..
a) knowing that cancer is there, but you may get hit by a bus before it kills you, can still inform some medical care decisions
b) the 12 authors of that paper have probably put a bit of thought into the usefulness and efficacy of this kind of very early detection, and concluded it was worth reporting on their research
I've just heard that for stuff like prostate cancer, a diagnosis can be misleading, because sometimes it can take 20+ years to kill you. If you get it when you're 70, it's probably not worth going through surgery or chemo because you'll likely die of heart disease or another cancer before that anyway.
Nah. It's not how science is done. You fill a lot of paperwork to ask for money and then a lot of paperwork to ask for permision to use human, and after the study is finished you must publish whatever positive result you got. Otherwise you will never get more money, or will be fired, or your students will not finish their Ph.D., or never get a position.
My guess is that they actuallly think that it's a important topic and that it's an important new tool. Everyone thinks that thir own topic is important.
About the efficacy, it's an early study. They show that the method somewhat works and it may be a good idea to continue improving the method to get more accurate diagnosis, perhaps distingish the different types of cancer, or perhaps it's a dead end.
About the usefulness, it's more difficult to evaluate. It's a decition that should be made by a team with a brader vision that can analyze the alternatives and the cost of each one. The research team has always a narrow vision.
> Scientists at the University of Oxford studied blood samples from more than 44,000 people in the UK Biobank, including over 4,900 people who subsequently had a cancer diagnosis.
It looks like the kind of study that has to present a report after it's completed and adding a publushed paper in Nature Whatever is a huge win. Nobody is fired for publishing in Nature.
Total Protein Initial Screen (g/L): 87 (normal range 61-84)
Immunoglobulin IgA (g/L): 4.9 (normal range < 4.8)
Immunoglobulin IgG Initial Screen (g/L): 18.5 (normal range 5.0 - 15.0)
Before I donate I have to sign something that says, among other things "We're going to test your blood for AIDS and tell you if you have it, so if you don't want to know don't donate". I hadn't thought about the other things they test for but of course they don't want blood with Leukemia in it either.
I hope all will turn out good for you, and wishing you the best of luck.
> they came back saying there were proteins present.
I think probably there is a bit of a Chinese whisper kind of misunderstanding here. Your blood will contain proteins. It must. Everyone's blood does. For example hemoglobin is a type of protein which makes your red blood cells able to carry oxygen.
What they probably told you is that they found the wrong quantity or the wrong kind of proteins.
Wishing you the best!
Total Protein Initial Screen (g/L): 87 (normal range 61-84)
Immunoglobulin IgA (g/L): 4.9 (normal range < 4.8)
Immunoglobulin IgG Initial Screen (g/L): 18.5 (normal range 5.0 - 15.0)
> con una concentración de 600-1800 mg por 100 mL
IANAMD. It looks like most of the time the increase can be produced by many common infections that are not dangerous. I strongly recomend to get a second opinion before starting some invasive procedure.
> Little evidence for protein associations was observed in these data for cancers of the pancreas, thyroid, lip and oral cavity, or melanoma after correcting for multiple tests
From the study https://www.nature.com/articles/s41467-024-48017-6
> More aggressive cancers, such as pancreatic cancer, tend to release more cell-free DNA into the bloodstream at early stages and are more likely to be detected by the Galleri test.
It’s a shame the US doesn’t have any way to quickly order non-invasive tests. Tests often only ordered when you are symptomatic. Even in those cases, you often get the bare minimum.
Have seen doctors personally and as an observing third party totally write them off. Instead of diagnosing, prescribe meds and treat symptomatically.
This is really exciting though, especially when mixed with other cancer treatments the ability to catch and deal with this is fascinating. How long until a theoretical, "Oh we detected some cancer cells in your regular blood work, here is a shot to deal with it" like we treat many other things.
But it is hard to tune so that it is practical enough to be deployed in routine healthcare. Efforts so far have not been sensitive or specific enough.
Maybe the depression and stress can make you more sick, let alone the effect on your family should you announce it
I'd like to get a rough estimate of how many moles I have at least once a year if it wasn't a huge effort.
This research is a high quality longitudinal retrospective study of protein cancer biomarkers, not cfDNA. Protein biomarkers are a complementary signal that has the potential to boost the sensitivity and precision of these tests, especially when the signals are combined together.
How low is the false positive rate?
GRAIL is available today, this test will need to be validated and commercialized
I suppose if you have enough of these markers they could schedule routine testing earlier than usual, say 40 instead of 45 for colonoscopy, mammogram, etc.
This applies both to employer plans and the ACA plans on healthcare.gov, where you can get a quote without giving them any health data at all.
It seems reasonable not to let people over 65 wait until they have cancer before purchasing supplemental insurance.