Some thoughts on this as someone working on circulating-tumor DNA for the last decade or so:
- Sure, cancer can develop years before diagnosis. Pre-cancerous clones harboring somatic mutations can exist for decades before transformation into malignant disease.
- The eternal challenge in ctDNA is achieving a "useful" sensitivity and specificity. For example, imagine you take some of your blood, extract the DNA floating in the plasma, hybrid-capture enrich for DNA in cancer driver genes, sequence super deep, call variants, do some filtering to remove noise and whatnot, and then you find some low allelic fraction mutations in TP53. What can you do about this? I don't know. Many of us have background somatic mutations speckled throughout our body as we age. Over age ~50, most of us are liable to have some kind of pre-cancerous clones in the esophagus, prostate, or blood (due to CHIP). Many of the popular MCED tests (e.g. Grail's Galleri) use signals other than mutations (e.g. methylation status) to improve this sensitivity / specificity profile, but I'm not convinced its actually good enough to be useful at the population level.
- The cost-effectiveness of most follow on screening is not viable for the given sensitivity-specificity profile of MCED assays (Grail would disagree). To achieve this, we would need things like downstream screening to be drastically cheaper, or possibly a tiered non-invasive screening strategy with increasing specificity to be viable (e.g. Harbinger Health).
tptacek · 4m ago
This seems like yet another place where the base rate is going to fuck us: intuitively (and you've actually thought about this problem and I haven't) I'd expect that even with remarkably good tests, most people who come up positive will not go on to develop related disease.
siliconc0w · 25m ago
Sadly health insurance in the US is unlikely to pay for most preventative care because the followup costs of false-positives and that they are betting that down the line someone else will pick up the tab when you get sick decades later (like the government).
It's kind of why I'm favor of universal option to align financial incentives. Like given how sick the US population is, it probably makes sense to put a lot more people of GPL-1s and invest in improving their efficacy and permanence. Like nationalize-the-patent COVID-operational-warp-speed level urgency. There are over 100M Americans that are pre-diabetic, the cost of treating a diabetic is about 20k/yr. So $4 trillion in new costs, on top of the misery and human suffering.
johnisgood · 7m ago
It is sad that prevention is not something the US considers very important.
mikert89 · 1h ago
The big secret is that they could detect cancer very early in most people, but the health care companies don't want to pay for the screening. You can pay out of pocket for these procedures. I was told this by a cancer researcher
EDIT:
Adding these caveats:
1. There is a ton of nuance in the diagnosis, since most people have a small amount of cancer in their blood at all times
2. The screenings are 5-10k + follow up appointments to actually see if its real cancer
3. All in cost then could be much higher per person
4. These tests arent something that are currently produced to be used at mass scale
doctoring · 1h ago
The not so big secret is that we can detect cancer early in a lot of people, but we also would detect a lot of not-cancer. We don't currently know the cost/benefit of that tradeoff for all these new types of screening, and therefore insurers and health systems are reluctant to pay the cost of the both screening and the subsequent workup. This is not just a financial consideration, though the financial part is a big part -- the workup for those that end up as not-cancer has non-negligible risks for the patients as well (I have had patients of mine suffer severe injury and even die from otherwise routine biopsies), and on top of that, some actual cancers may not really benefit from early discovery in the first place.
This is not to downplay the potential benefit of early cancer detection... which is huge. And in the US/UK anyway, there are ongoing large trials to try to figure some of this stuff out in the space of blood-based cancer screening, as part of the path to convincing regulatory bodies and eventual reimbursement for certain tests. As mentioned, you can currently at least get the Galleri test out of pocket (<$1k, not cheap, but not exorbitant either), as well as whole body MRIs (a bit more expensive, ~$2-5k).
PaulHoule · 13m ago
Or cancers that aren't clinically relevant.
Many prostate cancers, for instance, are slow growing and won't kill you before something else does. If you try to take that kind of cancer out surgically or zap it with radiation or chemo the side effects could be severe.
mikert89 · 1h ago
Yeah, after a detection there is alot of work to determine if what they detected should be worried about. But this doesnt take away from the fact that cancer can be detected very early, and these screenings could easily save your life
jmcgough · 1h ago
There's not a lot of evidence that full body MRIs are beneficial. A lot of people have pre-cancerous growths that may or may not become cancer in the future, so you may just be giving them unnecessary surgery, and surgeries are not risk-free. If you don't operate, they might develop an anxiety disorder.
We do a lot of CT imaging in the emergency department and it sucks if we incidentally find an abnormal growth in a young patient's CT head. These are usually benign and often not worth performing brain surgery to get a biopsy.
ospray · 59m ago
I had one at detected at 5mm close to the amigdala and they just scanned again in 3-6 months on MRI to prove it wasn't growing. That was a decade ago.
rscho · 1h ago
... or could do you harm, which is an important point.
ospray · 1h ago
To clarify is the harm that many healthy people would stress while it was confirmed the detection was not cancer?
rscho · 55m ago
No, the potential harm comes from follow-up tests. That's why screening strategies are designed by professionals. It's a pretty complex field, and all the people here fielding their opinions on how we should proceed about tests don't have a single idea about the implications of their theories.
mikert89 · 44m ago
this is medical gate keeping ("only the holy priests can practice medicine"), please take this attitude elsewhere
_coveredInBees · 23m ago
What a ridiculous statement to make. No wonder the US is in the state it is in. Lets let the ignorant and uninformed decide on policy rather than the scientific community and experts. What could possibly go wrong?
lm28469 · 36m ago
I think people like you should take their opinions elsewhere tbh, this forum is full of techbros with overinflated egos who think vibe coding chat apps and curing cancer are somewhat similar. It's OK to admit you don't know jack shit about complex topics out of your area of expertise, and just because you're an expert in a field doesn't mean your opinions and skills are transferable to another
rscho · 28m ago
Honestly, you don't have access to the necessary data to make rational decisions. That's not gatekeeping, it's logic. I don't have access to it either, although I'm indeed a healthcare pro. Screening strategies are a hyperspecialized domain and only experts somewhat understand what they're doing. It's just like making theories about what the CERN guys should be doing while not having passed physics 101 with no access to experimental data. That's why I'm just saying: you're certainly allowed to question, but you certainly can't make up assertions either.
DiscourseFan · 1h ago
Most healthy, active people who eat decently, get enough rest, and avoid drinking and smoking, will be able to eliminate cancer as it comes up. The only people who would benefit from these screenings are already unhealthy and cancer might be just one of many potential conditions they could experience—the goal of healthcare is not to dedicate an inordinate amount of resources for procedures that may amount to not much of any long term benefit.
People talk about the “immune system” but they are really referring to a number of systems the body uses to regulate itself, more or less successfully, around environmental pressures. The body is a system under tension, sometimes extreme tension leads to extreme success (success here being growth of power), sometimes it breaks the body, and sometimes the systems have been slowly failing for a while, and most treatments will not help. Medicine is only useful in the specific case where the power of the body would be promoted if not for one thing, that the body would be healthy, at least manageably so, without that issue.
cogman10 · 51m ago
> Most healthy, active people who eat decently, get enough rest, and avoid drinking and smoking, will be able to eliminate cancer as it comes up
Incorrect.
There are tons of cancers that hide and mask with symptoms common to other symptoms. Kidney cancer, for example, presents pretty similarly to both kidney stones and UTIs. Even blood in the urine isn't proof positive that anything is wrong beyond either of those conditions. And, by the time blood is in the urine, it's often too late.
Liver cancer is even worse. The first symptoms you get can be thought of as a simple pulled muscle, just a little ache in the back. By the time you have appreciable problems, like turning yellow, it's quite advanced and too late to really do much.
There are common cancers like colon, skin, breast, and prostate that more fit your description of being mostly harmless so long as you get regular screenings and eat healthy. But, for every part of the body, a cancer can form and the symptoms are very often invisible.
I'm unfortunately all too familiar with how cancer looks. My wife currently has stage 4 cancer that started as kidney cancer. She does not drink or smoke, gets enough rest, and is very active.
unsupp0rted · 37m ago
What's a good way for an otherwise healthy person to screen for kidney cancer, in terms of trade-offs?
Annual MRI?
cogman10 · 22m ago
IDK TBH. My wife had all the general recommended screenings. The only thing that showed potential problems was slightly elevated WBC. It was ultimately what they thought was a UTI that stayed a little too long that got us to get a CT and ultimately the diagnosis.
I do wonder if a 5 year whole body MRI or CT would be generally beneficial for the population. I don't think it needs to be Annual to have benefits.
The problem is it really isn't uncommon for your body to create random puss fill sacks all over the place. It's one thing our cancer doctor warned us about. My wife is now on a 6 month CT regimen and ultimately, they'll just ignore new lumps.
melling · 1h ago
Probably not true. It’s much cheaper to catch cancer early than to treat advanced cancer later
vasco · 50m ago
Yeah but then you'd go through life having biopsies all the time. If all people did a full body MRI almost everyone would have weird lumps that doctors would have to biopsy to be really sure, and then what do you do? Do you biopsy yourself every time some weird tissue appears? Most of those will be nothing and you'll be going through the complications of surgeries and anesthesia all the time just to always make sure.
cogman10 · 10m ago
Assuming MRIs weren't exorbitantly expensive, then the answer would probably be to simply rescan a month or 2 later and biopsy the lumps that don't go away.
rwmj · 42m ago
Assuming some future MRI technology which was very cheap, wouldn't you have MRIs at fairly regular intervals, to first see if the lump was growing or changing shape? And if this was being done at population scale, you'd train up an AI on the known outcomes, to have it flag up problems for a human to review.
HPsquared · 1h ago
That's true in the case someone actually does have cancer, but what about paying for all the negative tests?
mikert89 · 1h ago
Nope, the cost is 5-10k maybe more, and there is alot of nuance and follow ups to those detections
daedrdev · 1h ago
Doing this could be actively worse for you and society based on the false positive rate. Testing and accidental unneeded treatment carry very real risks that could lead to net suffering and more death or damage if enough people are tested.
mikert89 · 1h ago
This is a collectivist opinion on something which is very personal
daedrdev · 54m ago
Would you take a test if doing so statistically increases your probability of death?
Is it moral for a doctor to give a test they think is going to increase someone's chance of death.
rscho · 1h ago
It's not personal, it's perfectly rational statistics, i.e. epidemiology. Designing screening strategies is not an amateur's game.
andsoitis · 42m ago
> The big secret is that they could detect cancer very early in most people, but the health care companies don't want to pay for the screening.
thanks for adding the caveats; they suggest that there are good reasons why it isn't clear cut that health care companies should pay.
agumonkey · 1h ago
But what could we expect as fair price if mass scale production happens ?
delfinom · 1h ago
Health insurers would absolutely pay for the screennig if the sum spent on screening everyone was cheaper than long term cancer care.
It's the same reason they pay for annual physicals in the first place.
mikert89 · 1h ago
Nah the tests can go up to 10k per person
graeme · 1h ago
>if the sum spent on screening everyone was cheaper than long term cancer care
deadbabe · 1h ago
Wrong.
The usual story is that you’re just better off not knowing because you’ll end up doing more harm than good chasing every little suspicious diagnosis. Cancer happens all the time, but many times doesn’t lead to anything.
octaane · 1h ago
I actually know a little about this through my work. Cell-free DNA (CfDNA) Has been known about for a few decades, but has become more of a focus in recent years because of the advent of immunotherapies, which are often highly targeted drugs. CfDNA has also been used in "liquid biopsies" i.e, a simple blood draw, because it can help you profile the tumor and location of the cancer.
In my field, we all think that CfDNA testing will eventually become a standard thing that will go along with your annual physical's blood test, because it has predictive/preventative abilities.
drdrey · 18m ago
how actionable is the result? let's say you do detect trace amounts of tumoral DNA in your blood, what can you do? can you prevent it from developing into a full-on tumor if you don't even know where it is?
Quite interesting to me and first time I am hearing about this.
Question for you, what do you do when it shows you may have cancer? Do you speak to your physician? Surely, this will change your life even if it doesn't need treatment for next 6 years? Does the treatment change? Can the treatment be done based on those results?
So many questions.
I'm hoping we find more stuff for Alzheimer's. My aunt and now mother have it. I fear that I am next and I am too scared of doing the DNA test to check for genes.
octaane · 1h ago
You immediately bring the results to your doctor ASAP. They'll recommend follow-up testing since they want verification of third-party results and, well, are doctors and will know better about what to test for. If you do indeed have cancer, they will refer you to an oncologist who sub-specializes in that type of cancer.
the_arun · 1h ago
Isn’t $799 expensive for average families?
No comments yet
wiz21c · 1h ago
what about Europe ?
andsoitis · 38m ago
> what about Europe ?
what about Europe?
eej71 · 1h ago
Some life insurance companies offered it for free as part of a service to existing clients. Mine claimed they would not know the results. I hope its true because I did take them up on the offer. Results were statistically favorable for me so I appreciate the test for what it is.
Curious to see how these hold up over the long term.
andrewstuart · 2h ago
Blood testing sounds like a great opportunity for a startup…….
adamors · 1h ago
I wonder if they could work with very small amounts of blood …?
supportengineer · 1h ago
What if they took a small amount, but ran many different tests with it?
sylens · 1h ago
What if the testing unit was so small it could sit on your kitchen counter and send the results digitally to your doctor?
andrewstuart · 1h ago
What if major venture capitalists rallied around a charismatic founder and gave the startup huge financial backing.
cnst · 1h ago
What if the founder had a really nice deep voice to convince everyone that they're legit?
jjtheblunt · 1h ago
that made me chuckle.
then i remembered a month or so ago seeing this, and not knowing what to make of it.
- Sure, cancer can develop years before diagnosis. Pre-cancerous clones harboring somatic mutations can exist for decades before transformation into malignant disease.
- The eternal challenge in ctDNA is achieving a "useful" sensitivity and specificity. For example, imagine you take some of your blood, extract the DNA floating in the plasma, hybrid-capture enrich for DNA in cancer driver genes, sequence super deep, call variants, do some filtering to remove noise and whatnot, and then you find some low allelic fraction mutations in TP53. What can you do about this? I don't know. Many of us have background somatic mutations speckled throughout our body as we age. Over age ~50, most of us are liable to have some kind of pre-cancerous clones in the esophagus, prostate, or blood (due to CHIP). Many of the popular MCED tests (e.g. Grail's Galleri) use signals other than mutations (e.g. methylation status) to improve this sensitivity / specificity profile, but I'm not convinced its actually good enough to be useful at the population level.
- The cost-effectiveness of most follow on screening is not viable for the given sensitivity-specificity profile of MCED assays (Grail would disagree). To achieve this, we would need things like downstream screening to be drastically cheaper, or possibly a tiered non-invasive screening strategy with increasing specificity to be viable (e.g. Harbinger Health).
It's kind of why I'm favor of universal option to align financial incentives. Like given how sick the US population is, it probably makes sense to put a lot more people of GPL-1s and invest in improving their efficacy and permanence. Like nationalize-the-patent COVID-operational-warp-speed level urgency. There are over 100M Americans that are pre-diabetic, the cost of treating a diabetic is about 20k/yr. So $4 trillion in new costs, on top of the misery and human suffering.
EDIT:
Adding these caveats:
1. There is a ton of nuance in the diagnosis, since most people have a small amount of cancer in their blood at all times
2. The screenings are 5-10k + follow up appointments to actually see if its real cancer
3. All in cost then could be much higher per person
4. These tests arent something that are currently produced to be used at mass scale
This is not to downplay the potential benefit of early cancer detection... which is huge. And in the US/UK anyway, there are ongoing large trials to try to figure some of this stuff out in the space of blood-based cancer screening, as part of the path to convincing regulatory bodies and eventual reimbursement for certain tests. As mentioned, you can currently at least get the Galleri test out of pocket (<$1k, not cheap, but not exorbitant either), as well as whole body MRIs (a bit more expensive, ~$2-5k).
Many prostate cancers, for instance, are slow growing and won't kill you before something else does. If you try to take that kind of cancer out surgically or zap it with radiation or chemo the side effects could be severe.
We do a lot of CT imaging in the emergency department and it sucks if we incidentally find an abnormal growth in a young patient's CT head. These are usually benign and often not worth performing brain surgery to get a biopsy.
People talk about the “immune system” but they are really referring to a number of systems the body uses to regulate itself, more or less successfully, around environmental pressures. The body is a system under tension, sometimes extreme tension leads to extreme success (success here being growth of power), sometimes it breaks the body, and sometimes the systems have been slowly failing for a while, and most treatments will not help. Medicine is only useful in the specific case where the power of the body would be promoted if not for one thing, that the body would be healthy, at least manageably so, without that issue.
Incorrect.
There are tons of cancers that hide and mask with symptoms common to other symptoms. Kidney cancer, for example, presents pretty similarly to both kidney stones and UTIs. Even blood in the urine isn't proof positive that anything is wrong beyond either of those conditions. And, by the time blood is in the urine, it's often too late.
Liver cancer is even worse. The first symptoms you get can be thought of as a simple pulled muscle, just a little ache in the back. By the time you have appreciable problems, like turning yellow, it's quite advanced and too late to really do much.
There are common cancers like colon, skin, breast, and prostate that more fit your description of being mostly harmless so long as you get regular screenings and eat healthy. But, for every part of the body, a cancer can form and the symptoms are very often invisible.
I'm unfortunately all too familiar with how cancer looks. My wife currently has stage 4 cancer that started as kidney cancer. She does not drink or smoke, gets enough rest, and is very active.
Annual MRI?
I do wonder if a 5 year whole body MRI or CT would be generally beneficial for the population. I don't think it needs to be Annual to have benefits.
The problem is it really isn't uncommon for your body to create random puss fill sacks all over the place. It's one thing our cancer doctor warned us about. My wife is now on a 6 month CT regimen and ultimately, they'll just ignore new lumps.
Is it moral for a doctor to give a test they think is going to increase someone's chance of death.
thanks for adding the caveats; they suggest that there are good reasons why it isn't clear cut that health care companies should pay.
It's the same reason they pay for annual physicals in the first place.
The usual story is that you’re just better off not knowing because you’ll end up doing more harm than good chasing every little suspicious diagnosis. Cancer happens all the time, but many times doesn’t lead to anything.
In my field, we all think that CfDNA testing will eventually become a standard thing that will go along with your annual physical's blood test, because it has predictive/preventative abilities.
Ageless also provides many other longevity therapies.
I get it every year. So far, so good!
Question for you, what do you do when it shows you may have cancer? Do you speak to your physician? Surely, this will change your life even if it doesn't need treatment for next 6 years? Does the treatment change? Can the treatment be done based on those results?
So many questions.
I'm hoping we find more stuff for Alzheimer's. My aunt and now mother have it. I fear that I am next and I am too scared of doing the DNA test to check for genes.
No comments yet
what about Europe?
Curious to see how these hold up over the long term.
then i remembered a month or so ago seeing this, and not knowing what to make of it.
https://siphoxhealth.com/