21 ms·

Experimental blood test detects cancer up to four years before symptoms appear

650 points by prawn 6y ago

iworkfromhome 6y ago
Cancer is difficult to detect early. We must care more about ourselves.
scandox 6y ago
This makes me think of an article I read about prostate cancer detection. Apparently, it is possible to detect the possibility of prostate cancer many, many years before it is going to develop with a more sensitive, modern test. Once the detection is made both patient and doctor are not in a position to ignore it. At the same time treatment may well be premature or not recommended. But the doctor is left with a dilemma because it may appear they did not take action on something they knew. That at least was the general topic of the article. The question it raises is interesting: is it sometimes too early to know.
- hannob 6y ago
  This is widely discussed in medical circles, but the real problem is a different one: It's sometimes hard to know what helps and what doesn't. You may see something that may lead to a cancer. But you really don't know. It may be a) harmless, b) lead to a cancer, c) a mistake in your test. If it's b) then treating it early is good. If it's a) or c) then treating it early will ultimately harm the patient. If your test finds mainly a) and c) then your test may ultimately do more harm than good.
  - sterlind 6y ago
    Isn't this the idea behind watchful waiting? You have an early signal so you follow up with periodic tests to see if it goes away or shows signs of malignancy. Eventually we'll have studies that show the conditional probability of different cancer outcomes based on these early signals, and from there we'll have a protocol to get the best outcomes, reducing the chance of malignant cancer while minimizing cost and medical intervention.
  - forgotmypwbctbi 6y ago
    it is at minimum an early warning for lifestyle change
  - jfk13 6y ago
    Even if you could predict with certainty that the patient is going to develop cancer in 10 years, and you know of a course of treatment you could undertake that will ultimately prevent that cancer developing, you still may not be able to say whether this is the best use of the patient's time and resources today. (And the patient can't be sure either.)
    - shard 6y ago
      So the best course to take seems to be a combination of the probabilities of each case along with the risk tolerance of the patient, thus it is not a question the medical community can answer, but needs to be an individual discussion with each patient.
- DanBC 6y ago
  Early detection of prostate cancer with PSA testing and digital rectal exam: https://www.hardingcenter.de/en/early-detection-prostate-cancer-psa-testing-and-digital-rectal-exam https://www.hardingcenter.de/en/early-detection-prostate-can... > With or without screening, 7 out of every 1,000 men died from prostate cancer over a time period 11 years. But in the screening group additional men were harmed by side effects of surgery.
  - shard 6y ago
    I am not sure what percentage of patients still require surgery as opposed to the more modern radiation treatments. My father's radiation treatment was painless except for the placement of the 3 tracking markers in his prostate, and although his side effects were more severe than most, they have disappeared after 3 months. So if prostate cancer treatment does not affect eventual death from the cancer over 11 years, then the questions are whether the treatment improve QOL during the 11 years, and whether the onset is delayed within that 11 years.
- pintxo 6y ago
  Prostate cancer is somewhat unique by having a very sensitive blood marker (PSA) being available which can be monitored easily over time. And yes, there is an (I would say) ongoing debate about the value of using PSA to detect early cancers. Obviously detecting cancer early is a win. But the downside of this early detection is over-treatment of low-risk cancers. Standard therapy for prostate cancer is the removal of the prostate, but this surgery has a somewhat high (up to ~10-15%) risk of impotence and incontinence (depending on the quality of the surgeon), which can obviously impact life quality quite massively. Current strategy (in the US) seems to basically stop broad usage of PSA testing, which gets rid of the problem of detecting low risk cancers, but at the cost of delaying the identification of high risk cancers. This is visible in the falling rate of newly diagnosed prostate cancer patients in the US. This feels like not solving the actual problem (distinguishing low risk from high risk tumors) but glossing over the problem by not actively working on detecting it anymore.
  - DanBC 6y ago
    > but at the cost of delaying the identification of high risk cancers. This is visible in the falling rate of newly diagnosed prostate cancer patients in the US. Importantly, it doesn't seem to affect mortality rate of prostate cancer, nor all cause mortality. People focus a lot on 5 year survival rate, but sometimes they don't really understand what this means. If I die at 75 does it matter if my cancer is detected when I'm 68 vs 73?
    - pintxo 6y ago
      I tend to agree that this is not such a relevant topic for the average prostate cancer age group which is 70+. Here most might die with prostate cancer but not from prostate cancer. But in the lower age groups 40-60 early detection should IMHO be the aim.
    - thaumasiotes 6y ago
      > If I die at 75 does it matter if my cancer is detected when I'm 68 vs 73? Yes, it matters in both directions. One way is that the cancer might cause you to suffer in other ways, e.g. by metabolizing all of your food, causing you to lose large amounts of weight. If this is addressable (not at all a sure thing!), then knowing earlier is probably better. The other way is that you might not be suffering. In that case, given that your death is fixed, knowing earlier is obviously worse. I've never seen someone die of cancer without being treated beforehand. I understand it's a horrible, painful death. That said, the treatments we apply to someone dying of cancer also make for a horrible, painful death; there definitely is a point at which the treatment is worse than the cancer. Another wrinkle is that treatment may give you a few horrible months, then a few not-so-bad-years before your cancer comes back, and then the horribleness resumes. Those years in the middle are worth something, even if the time at which you die is fixed. If we ignore brief-to-medium remissions, and the hypothetical patient's time of death is fixed, then the obvious recommendation is to avoid all treatment and commit suicide when your quality of life drops too low. But the uncertainty we have in reality makes that difficult.
- sradman 6y ago
  Stomach cancer, for one, is easy to remove surgically if detected early but it does not exhibit symptoms until it is often too late. I suspect that early warnings would trigger targeted endoscopy procedures. The pathogenesis of prostate cancer may not be representative of other cancers.
  - elric 6y ago
    Same with bowel cancer. Easily treated if found early. There are at home test kits which can detect small amounts of blood in stool -- often an early warning sign. And while unpleasant sounding, colo(no)scopy is pretty uninvasive.
- henearkr 6y ago
  This is an incredible confusion, and I'm angry to see so many medical authorities and administrations taking the same stance: no, it's never too early to know. The more the information the better everything. What could be too early is to act, supposing that by "act" is meant any predefined medical action. However why would it be any "too soon" for an awareness awakening by the sick individual that would bring a healthier lifestyle? Last thing I'd like to add, you just have to tell the individual about the trade-off and risks of the early act too, and this additional information will be enough to cancel any supposed danger of the early diagnostics information. When you think that giving some information is dangerous, then actually it's because you need to provide the targeted individual even more of what info you have.
  - foldr 6y ago
    > it's never too early to know I don't see this. Suppose, hypothetically, that we could detect right now every illness or condition that you're ever likely to develop in the course of your life. Do you really want to read through that list? You're better off not worrying about it and enjoying your life.
    - echelon 6y ago
      > You're better off not worrying about it and enjoying your life. I would rather have all of the information upfront so that I can make better informed decisions. We're all going to die. I'm not going to shy away from that by pretending it won't come.
      - foldr 6y ago
        There's no 'pretence' involved in not reading the list. I'm perfectly aware of my mortality. I just don't see any value in placing bets on what's going to kill me.
        shard 6y ago
        Everyone is living with an invisible list made up by them in their minds. This is what drives people to exercise, eat healthy foods, get vaccinated, and wash their hands. This just clarifies the list, perhaps adding some items, perhaps changing the priorities.
- thaumasiotes 6y ago
  > Apparently, it is possible to detect the possibility of prostate cancer many, many years before it is going to develop with a more sensitive, modern test. Once the detection is made both patient and doctor are not in a position to ignore it. I'll tell you a story from when my mother was in medical school. There was a class one day in which the students were given a pile of slides of prostate samples and told to identify the cancerous one. Many, many questions ensued, of the form "This looks kind of cancerous. Is this the slide?" Eventually the professor announced to the class "look, there's a bit of cancer in everyone's prostate. The goal here is to find the slide with OBVIOUS cancer." And this is, to the best of my knowledge, still the state of things in prostate cancer today. All prostates are cancerous. A man who lived long enough would eventually be killed by prostate cancer -- a cancer detectable long, long before he actually died. But most men die of other things, because prostate cancer develops so slowly. Ignoring prostate cancer is in fact a common way to handle it, if the patient is old enough or the cancer is small enough when detected. The technical term for this is "watchful waiting".
  - pintxo 6y ago
    A pathologist once told me the likelihood of having prostate cancer is basically you age: 50 -> 50%, 70 -> 70%, ...
    - demadog 6y ago
      103% for my grandfather then
      - pintxo 6y ago
        You might want to apply a min(calcProp(), 1)
        thaumasiotes 6y ago
        Maybe he has one advanced tumor and one polyp that's about 3% more cancerous than expected.
      - deleted 6y ago
- raducu 6y ago
  I have a SNP (according to ancestry) that gives me ~5X the chance to get prostate cancer. What treatment is available for prostate cancer, besides debilitating surgery?
  - HeadsUpHigh 6y ago
    Chemo and radiotherapy, the whole trifecta. Some new ways of implanting small radioactive disks straight into the prostate with a minimally invasive procedure are being developed as well.
  - scandox 6y ago
    Someone I know had robotic keyhole surgery and they were up and walking about in a week. That was a man in his 60s with mediocre health. He went to the Henry Ford Medical Centre.
    - pintxo 6y ago
      Keyhole is the key here to walk out asap. The "roboter" is not delivering that much in terms of quality of outcome or speed of recovery.
  - pintxo 6y ago
    Surgery, done by good surgeons, has low (single digit) complication rates. Tip: Ask your surgeon how often he does this specific surgery. Removing the prostate requires foremost experience to not severe any nerves surrounding the organ, which are important for potency and continence. As you would not want your cars brake firmware to be written by someone who usually writes marketing apps, you do not want to get this surgery from anyone who has not specialized on it. There are specialists who do this surgery >200 times a year.
    - raducu 6y ago
      I'm in my mid thirties, I'll look into PSA, and my father has prostatitis, but no family history of prostate cancer(my grandfather died 86 years old, but lived a much healthier life than me or my father). So I'll definitely keep it under observation, I just hope those percentages will improve in the next decades.
- Zenst 6y ago
  >That at least was the general topic of the article. The question it raises is interesting: is it sometimes too early to know. reply Bit like near earth objects, we can detect one far far away and whilst could be 95% sure it will hit, either way, unable to do anything to it until it gets closer. But always good to know ahead of time so can prepare and eventually able to deal with it further out.
- abalone 6y ago
  I’ve studied this topic a lot and consulted with top prostate cancer centers of excellence. Key points: - Disregard what you may read about PSA testing / screening being “more harm than good”. This was a relatively recent recommendation in the US by a non specialist task force that is looking to be bad advice. Studies now show it has led to an increase in metastatic cancer.[1] You don’t want that. - Every man should get their PSA checked by 45, or earlier if it runs in your family. It is a simple blood test. We are lucky to have a tool like that at our disposal; not always the case for other cancers. - Prostate cancer treatment can have major impacts on quality of life including sexual function. You are much better off getting treated before it reaches stage 3. Quality of life is better. This is not reflected in mortality stats. - People do die from it and it is a slow and painful death like most cancers. About 2.4% of men die from prostate cancer.[2] With early detection it is very treatable, however, even curable. - There are advances in screening techniques. PSA is an imperfect but easy and cheap initial screening tool. Doing it early can also establish a baseline. If it’s abnormal it just opens up a conversation and more screening options. Biopsies are also more accurate these days. Men, go ahead and get your PSA test. [1] https://jamanetwork.com/journals/jamaoncology/fullarticle/2594540 https://jamanetwork.com/journals/jamaoncology/fullarticle/25... [2] https://www.cancer.org/cancer/prostate-cancer/about/key-statistics.html https://www.cancer.org/cancer/prostate-cancer/about/key-stat...
sradman 6y ago
Original paper [1]: > Here we report the preliminary results of PanSeer, a noninvasive blood test based on circulating tumor DNA methylation... I’m very surprised that parts of the methylome, the per-cell state-machine that controls what genes are transcribed, have sufficient serum concentration to be detected. I suspect that this approach should work for any diseased cell targeted by the immune system as long as the disease results in a small but unique methylation signature. [1] https://www.nature.com/articles/s41467-020-17316-z https://www.nature.com/articles/s41467-020-17316-z
- patall 6y ago
  With most of these (cell free DNA) assays, its not a single site that you are measuring but a statistical aggregate about profiles that have been defined for a certain cell type. If you know the overall profile of prostate cells and the profile of normal blood, you can subtract the expected profile from a patient sample and the analyse the left-over fraction for whether it is just noise or is matching to one or multiple known cell types. The surprise from this publication is only that they detect such signatures 4 years earlier than other non-invasive testing. (although nobody in the cfDNA field would be surprised about that).
- gww 6y ago
  There are newer methods that use antibodies to enrich for methylated dna prior to sequencing [1]. The method increases sensitivity as the majority of plasma cfDNA is unmethylated and hematopoietic in origin. [1] https://www.nature.com/articles/s41586-018-0703-0 https://www.nature.com/articles/s41586-018-0703-0
- sradman 6y ago
  gww and patall both point out that this is related to cfDNA [1]: > Circulating free DNA (cfDNA) are degraded DNA fragments released to the blood plasma. [1] https://en.wikipedia.org/wiki/Circulating_free_DNA https://en.wikipedia.org/wiki/Circulating_free_DNA
deleted 6y ago
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underdeserver 6y ago
Breakthrough medicinal research is great, but we should always remember that even most promising results - see the COVID vaccines/treatments we've been hearing about over the past few months - end up not viable at the late stages. So, cautious optimism, not great hope and sensationalism, is the right attitude to take here.
- qayxc 6y ago
  “We are still a ways away from having an accurate blood-based ‘pan-cancer’ screening test. But it is not impossible to achieve,” Pritchard says. I think the article itself got you covered there.
boringcuriosity 6y ago
If this could happen, I would like to envade Mars
kermitje 6y ago
The real false positive rate is much higher than the 5% reported. The false positive rate reported is ~5% in a sample with an equal number of people that did and did not develop cancer, while the ratio in reality is 1/122 (i.e., 1000 people developed cancer, 122000 did not). Could still be a useful development, but it does make me wonder about the cost/benefits at this stage.
- deleted 6y ago
  [deleted]
- patall 6y ago
  Eventually, this is all about cost. cfDNA assays are targetted to in the end cost less than 100 bucks per sample which for the detection of a single cancer puts you in the range of $12000 for one tumor diagnosis. Ideally, you can now decrease the therapy cost of that one diagnosis while also boosting survival chances. And $12000 is not much in tumor therapy. The key however here is the advanced prognosis that may allow totally different therapeutic approaches, extend the understanding risk factors etc. and the fact that you do not need to have a specialist on side, taking a blood sample can in principle be done at home and the rest is automatic. Edit: Oh, and 5% false positives is not that bad actually, I do not have numbers is my head but would expect other essays like breast cancer screening to be also in that range.
  - helsinkiandrew 6y ago
    5% false positives on people who have some symptoms of cancer isn’t bad. But 5% of a ‘high risk group’ could be a lot - particularly if the cancer is too early to confirm detection any other way yet and possibly not treatable for several years.
    - minerjoe 6y ago
      They'll find something to sell in this case.
      - 6y ago
billpg 6y ago
We call it the "Do I qualify for health insurance?" test.
civil_engineer 6y ago
If false positive rate is 5%, and 1000 of 123,000 were diagnosed with cancer over 10 years, this test would produce 6,100 false positives, and 1,000 true positives. Six out of seven positive tests would be false positives.
- whichquestion 6y ago
  Would having 6000 false positives be okay for being able to find the 1000 true positives? Would further testing be able to show whether or not there is actually cancer? Maybe they will be able to improve the accuracy of the test enough where the false positive rate of the test is <<5%...
  - TeaDrunk 6y ago
    It also means that the test fails at detecting cancer more often than not, and will mean that if it detects a true cancer this time doctors will be inclined to not take it seriously because evidence/experience is that the test is useless
    - shard 6y ago
      I suppose this takes into account the fact that doctors are humans too, and humans are typically not good at statistics. The probability of cancer from a positive test rises from 0.8% to 14.1%, a significant increase, and seems to warrant a closer look, from a layman's point of view at least.
  - mtts 6y ago
    > Would having 6000 false positives be okay for being able to find the 1000 true positives? I’d say no. That’s 5000 people who are told they might have cancer while in fact they don’t and who will then undergo further testing that is at best traumatic and at worst extremely invasive if not outright damaging. Take intestinal cancer, for example. You can get screened for that and if you screen positive, they will take a biopsy - a fairly unpleasant and not entirely risk free procedure. Then it gets worse. If the biopsy shows some part of your intestines isn’t quite in order (a likely outcome, though not necessarily one that indicates cancer) they will take out that bit of intestine, just to be safe. This is a very invasive procedure and because it’s your intestines we’re talking about, you digestive system will be seriously out of whack for a while - if it ever heals completely - seriously and significantly degrading your quality of life. All this for a, let’s use your figures, 1 in 6 chance that you might have had cancer.
cell9840179419 6y ago
Call me silly, but, methylation is a hallmark of aging as well. So all cancer patients would show methylation, but all methylation will not indicate cancer. If that were the case, cancer would be the only cause of natual death.
- DangerousPie 6y ago
  That's not what the test is doing. They are looking at methylation in specific places.
mchusma 6y ago
A good econ talk on why this kind of thing (improving cancer diagnostics) is by far the most promising "cure for cancer". http://www.econtalk.org/azra-raza-on-the-first-cell/ http://www.econtalk.org/azra-raza-on-the-first-cell/ I hope we have many more tests like this that can be done frequently and add to the arsenal. Great work to these researchers.
- ramidarigaz 6y ago
  Azra Raza was also on the Mindscape podcast, really realy good interview. https://www.preposterousuniverse.com/podcast/2019/12/16/77-azra-raza-on-the-way-we-should-fight-cancer/ https://www.preposterousuniverse.com/podcast/2019/12/16/77-a...
Cirpop 6y ago
Interesting, especially considering pancreatic cancer. That one can be treated if caught early on, but it hardly ever is, making it incredibly lethal, even for a cancer to be.
TaupeRanger 6y ago
Guess it's time to share this again. "Cancer screening has never been shown to save lives" - Oncologist Vinay Prasad. Detection is not the problem. It's what to do once you find it. Iatrogenic harms are real. https://www.bmj.com/content/352/bmj.h6080 https://www.bmj.com/content/352/bmj.h6080 With better testing, we might be able to save some people, but we might also be subjecting a great deal more people to harms through unnecessary treatment and psychological trauma.
- jforman 6y ago
  You can't design interventions for problems that you cannot see. Detection alone doesn't save lives, but it is a necessary step to the discovery of interventions that do.
- eloff 6y ago
  There's a lot to this, if you look hard enough you'll find something wrong. But that something wrong probably would have never progressed into something that kills you - however the interventions you then undergo are not without risk. Like if you have the slow-growing prostate cancer, you'll die of something else. But if you operate you're taking risks of surgery and lifetime incontinence, and might spread it elsewhere in the body. However, I still think early detection is an important first step to finding better interventions. Once you know it's there you can start to come up with less risky/invasive treatments. The odds of dealing with it at an early stage are so much better and the scope of the intervention required so much smaller.
jliptzin 6y ago
Cures and vaccines would be great but I feel like we are missing an opportunity with improved testing not just for cancer but also for infectious diseases. Imagine a toilet that can detect a UTI/STI or parasite or a monitor in my room that can detect airborne viral particles which might tell me I have a cold, flu or COVID before I even know about it. Then I know to treat and isolate before spreading it to others. If we had cheap, instant, accurate tests for infectious diseases then I’d imagine we could begin eradicating some of them.
vondur 6y ago
Seems really cool, but how many cancers progress from something minor to something life threatening? Some of the treatments can be pretty invasive/lot's of side effects. I wonder how much cancer the body can deal with on it's own and never progresses?
rsync 6y ago
If you care even the smallest amount about your own, personal, cancer risk you should immediately cut your feeding window to 8 (or even 6) hours per day and start walking a few miles, daily. I did not mention "fasting" or "diet" or "weight loss". Just condense your caloric input into a tighter window and walk more than zero miles per day. It's silly to pursue fine grained, specific optimizations when the juiciest, lowest hanging fruit is stubbornly, inexplicably, left unpicked.
- wonderlg 6y ago
  Source? There’s so much information about nutrition online that one should not just trust the first comment found on a forum. Edit: I’m referring to the “feeding window”
  - waterhouse 6y ago
    I think the common term is "intermittent fasting" (despite the protest about the word "fasting"), which covers a range of strategies—"time-restricted feeding" is the type where the fasting period is less than a day. https://en.wikipedia.org/wiki/Intermittent_fasting#Types https://en.wikipedia.org/wiki/Intermittent_fasting#Types There is at least some research supporting the claim that time-restricted feeding inhibits the growth of cancer in humans: "In repeated-measures Cox proportional hazards regression models, fasting less than 13 hours per night (lower 2 tertiles of nightly fasting distribution) was associated with an increase in the risk of breast cancer recurrence compared with fasting 13 or more hours per night (hazard ratio, 1.36; 95% CI, 1.05-1.76)." https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4982776/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4982776/ There have also been studies in mice: "Results and Conclusion: TRF had a dramatic effect, reducing tumor growth in obese mice fed a high fat diet (HFD) to levels seen in lean mice. Tumor growth and initiation was also delayed in the transgenic PyMT model of mammary tumorigenesis. Our results further suggest that the antitumor effect of TRF is at least partially mediated by reducing hyperinsulinemia, suggesting that this intervention may be effective in breast cancer prevention and therapy." https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6552025/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6552025/
Balgair 6y ago
To be clear here: these are only circulating cancers. Cancers that break through mesenchymal barriers or can affect the blood are not very common. It's great, amazing even, if you can catch them. But many cancers will never show up in the blood. Still, great work!
skumar88023 6y ago
Very well

650 points by prawn 6y ago

Cancer is difficult to detect early. We must care more about ourselves.

This makes me think of an article I read about prostate cancer detection. Apparently, it is possible to detect the possibility of prostate cancer many, many years before it is going to develop with a more sensitive, modern test. Once the detection is made both patient and doctor are not in a position to ignore it. At the same time treatment may well be premature or not recommended. But the doctor is left with a dilemma because it may appear they did not take action on something they knew. That at least was the general topic of the article. The question it raises is interesting: is it sometimes too early to know.

hannob 6y ago
This is widely discussed in medical circles, but the real problem is a different one: It's sometimes hard to know what helps and what doesn't. You may see something that may lead to a cancer. But you really don't know. It may be a) harmless, b) lead to a cancer, c) a mistake in your test. If it's b) then treating it early is good. If it's a) or c) then treating it early will ultimately harm the patient. If your test finds mainly a) and c) then your test may ultimately do more harm than good.
- sterlind 6y ago
  Isn't this the idea behind watchful waiting? You have an early signal so you follow up with periodic tests to see if it goes away or shows signs of malignancy. Eventually we'll have studies that show the conditional probability of different cancer outcomes based on these early signals, and from there we'll have a protocol to get the best outcomes, reducing the chance of malignant cancer while minimizing cost and medical intervention.
- forgotmypwbctbi 6y ago
  it is at minimum an early warning for lifestyle change
- jfk13 6y ago
  Even if you could predict with certainty that the patient is going to develop cancer in 10 years, and you know of a course of treatment you could undertake that will ultimately prevent that cancer developing, you still may not be able to say whether this is the best use of the patient's time and resources today. (And the patient can't be sure either.)
  - shard 6y ago
    So the best course to take seems to be a combination of the probabilities of each case along with the risk tolerance of the patient, thus it is not a question the medical community can answer, but needs to be an individual discussion with each patient.
DanBC 6y ago
Early detection of prostate cancer with PSA testing and digital rectal exam: https://www.hardingcenter.de/en/early-detection-prostate-cancer-psa-testing-and-digital-rectal-exam https://www.hardingcenter.de/en/early-detection-prostate-can... > With or without screening, 7 out of every 1,000 men died from prostate cancer over a time period 11 years. But in the screening group additional men were harmed by side effects of surgery.
- shard 6y ago
  I am not sure what percentage of patients still require surgery as opposed to the more modern radiation treatments. My father's radiation treatment was painless except for the placement of the 3 tracking markers in his prostate, and although his side effects were more severe than most, they have disappeared after 3 months. So if prostate cancer treatment does not affect eventual death from the cancer over 11 years, then the questions are whether the treatment improve QOL during the 11 years, and whether the onset is delayed within that 11 years.
pintxo 6y ago
Prostate cancer is somewhat unique by having a very sensitive blood marker (PSA) being available which can be monitored easily over time. And yes, there is an (I would say) ongoing debate about the value of using PSA to detect early cancers. Obviously detecting cancer early is a win. But the downside of this early detection is over-treatment of low-risk cancers. Standard therapy for prostate cancer is the removal of the prostate, but this surgery has a somewhat high (up to ~10-15%) risk of impotence and incontinence (depending on the quality of the surgeon), which can obviously impact life quality quite massively. Current strategy (in the US) seems to basically stop broad usage of PSA testing, which gets rid of the problem of detecting low risk cancers, but at the cost of delaying the identification of high risk cancers. This is visible in the falling rate of newly diagnosed prostate cancer patients in the US. This feels like not solving the actual problem (distinguishing low risk from high risk tumors) but glossing over the problem by not actively working on detecting it anymore.
- DanBC 6y ago
  > but at the cost of delaying the identification of high risk cancers. This is visible in the falling rate of newly diagnosed prostate cancer patients in the US. Importantly, it doesn't seem to affect mortality rate of prostate cancer, nor all cause mortality. People focus a lot on 5 year survival rate, but sometimes they don't really understand what this means. If I die at 75 does it matter if my cancer is detected when I'm 68 vs 73?
  - pintxo 6y ago
    I tend to agree that this is not such a relevant topic for the average prostate cancer age group which is 70+. Here most might die with prostate cancer but not from prostate cancer. But in the lower age groups 40-60 early detection should IMHO be the aim.
  - thaumasiotes 6y ago
    > If I die at 75 does it matter if my cancer is detected when I'm 68 vs 73? Yes, it matters in both directions. One way is that the cancer might cause you to suffer in other ways, e.g. by metabolizing all of your food, causing you to lose large amounts of weight. If this is addressable (not at all a sure thing!), then knowing earlier is probably better. The other way is that you might not be suffering. In that case, given that your death is fixed, knowing earlier is obviously worse. I've never seen someone die of cancer without being treated beforehand. I understand it's a horrible, painful death. That said, the treatments we apply to someone dying of cancer also make for a horrible, painful death; there definitely is a point at which the treatment is worse than the cancer. Another wrinkle is that treatment may give you a few horrible months, then a few not-so-bad-years before your cancer comes back, and then the horribleness resumes. Those years in the middle are worth something, even if the time at which you die is fixed. If we ignore brief-to-medium remissions, and the hypothetical patient's time of death is fixed, then the obvious recommendation is to avoid all treatment and commit suicide when your quality of life drops too low. But the uncertainty we have in reality makes that difficult.
sradman 6y ago
Stomach cancer, for one, is easy to remove surgically if detected early but it does not exhibit symptoms until it is often too late. I suspect that early warnings would trigger targeted endoscopy procedures. The pathogenesis of prostate cancer may not be representative of other cancers.
- elric 6y ago
  Same with bowel cancer. Easily treated if found early. There are at home test kits which can detect small amounts of blood in stool -- often an early warning sign. And while unpleasant sounding, colo(no)scopy is pretty uninvasive.
henearkr 6y ago
This is an incredible confusion, and I'm angry to see so many medical authorities and administrations taking the same stance: no, it's never too early to know. The more the information the better everything. What could be too early is to act, supposing that by "act" is meant any predefined medical action. However why would it be any "too soon" for an awareness awakening by the sick individual that would bring a healthier lifestyle? Last thing I'd like to add, you just have to tell the individual about the trade-off and risks of the early act too, and this additional information will be enough to cancel any supposed danger of the early diagnostics information. When you think that giving some information is dangerous, then actually it's because you need to provide the targeted individual even more of what info you have.
- foldr 6y ago
  > it's never too early to know I don't see this. Suppose, hypothetically, that we could detect right now every illness or condition that you're ever likely to develop in the course of your life. Do you really want to read through that list? You're better off not worrying about it and enjoying your life.
  - echelon 6y ago
    > You're better off not worrying about it and enjoying your life. I would rather have all of the information upfront so that I can make better informed decisions. We're all going to die. I'm not going to shy away from that by pretending it won't come.
    - foldr 6y ago
      There's no 'pretence' involved in not reading the list. I'm perfectly aware of my mortality. I just don't see any value in placing bets on what's going to kill me.
      - shard 6y ago
        Everyone is living with an invisible list made up by them in their minds. This is what drives people to exercise, eat healthy foods, get vaccinated, and wash their hands. This just clarifies the list, perhaps adding some items, perhaps changing the priorities.
thaumasiotes 6y ago
> Apparently, it is possible to detect the possibility of prostate cancer many, many years before it is going to develop with a more sensitive, modern test. Once the detection is made both patient and doctor are not in a position to ignore it. I'll tell you a story from when my mother was in medical school. There was a class one day in which the students were given a pile of slides of prostate samples and told to identify the cancerous one. Many, many questions ensued, of the form "This looks kind of cancerous. Is this the slide?" Eventually the professor announced to the class "look, there's a bit of cancer in everyone's prostate. The goal here is to find the slide with OBVIOUS cancer." And this is, to the best of my knowledge, still the state of things in prostate cancer today. All prostates are cancerous. A man who lived long enough would eventually be killed by prostate cancer -- a cancer detectable long, long before he actually died. But most men die of other things, because prostate cancer develops so slowly. Ignoring prostate cancer is in fact a common way to handle it, if the patient is old enough or the cancer is small enough when detected. The technical term for this is "watchful waiting".
- pintxo 6y ago
  A pathologist once told me the likelihood of having prostate cancer is basically you age: 50 -> 50%, 70 -> 70%, ...
  - demadog 6y ago
    103% for my grandfather then
    - pintxo 6y ago
      You might want to apply a min(calcProp(), 1)
      - thaumasiotes 6y ago
        Maybe he has one advanced tumor and one polyp that's about 3% more cancerous than expected.
    - deleted 6y ago
raducu 6y ago
I have a SNP (according to ancestry) that gives me ~5X the chance to get prostate cancer. What treatment is available for prostate cancer, besides debilitating surgery?
- HeadsUpHigh 6y ago
  Chemo and radiotherapy, the whole trifecta. Some new ways of implanting small radioactive disks straight into the prostate with a minimally invasive procedure are being developed as well.
- scandox 6y ago
  Someone I know had robotic keyhole surgery and they were up and walking about in a week. That was a man in his 60s with mediocre health. He went to the Henry Ford Medical Centre.
  - pintxo 6y ago
    Keyhole is the key here to walk out asap. The "roboter" is not delivering that much in terms of quality of outcome or speed of recovery.
- pintxo 6y ago
  Surgery, done by good surgeons, has low (single digit) complication rates. Tip: Ask your surgeon how often he does this specific surgery. Removing the prostate requires foremost experience to not severe any nerves surrounding the organ, which are important for potency and continence. As you would not want your cars brake firmware to be written by someone who usually writes marketing apps, you do not want to get this surgery from anyone who has not specialized on it. There are specialists who do this surgery >200 times a year.
  - raducu 6y ago
    I'm in my mid thirties, I'll look into PSA, and my father has prostatitis, but no family history of prostate cancer(my grandfather died 86 years old, but lived a much healthier life than me or my father). So I'll definitely keep it under observation, I just hope those percentages will improve in the next decades.
Zenst 6y ago
>That at least was the general topic of the article. The question it raises is interesting: is it sometimes too early to know. reply Bit like near earth objects, we can detect one far far away and whilst could be 95% sure it will hit, either way, unable to do anything to it until it gets closer. But always good to know ahead of time so can prepare and eventually able to deal with it further out.
abalone 6y ago
I’ve studied this topic a lot and consulted with top prostate cancer centers of excellence. Key points: - Disregard what you may read about PSA testing / screening being “more harm than good”. This was a relatively recent recommendation in the US by a non specialist task force that is looking to be bad advice. Studies now show it has led to an increase in metastatic cancer.[1] You don’t want that. - Every man should get their PSA checked by 45, or earlier if it runs in your family. It is a simple blood test. We are lucky to have a tool like that at our disposal; not always the case for other cancers. - Prostate cancer treatment can have major impacts on quality of life including sexual function. You are much better off getting treated before it reaches stage 3. Quality of life is better. This is not reflected in mortality stats. - People do die from it and it is a slow and painful death like most cancers. About 2.4% of men die from prostate cancer.[2] With early detection it is very treatable, however, even curable. - There are advances in screening techniques. PSA is an imperfect but easy and cheap initial screening tool. Doing it early can also establish a baseline. If it’s abnormal it just opens up a conversation and more screening options. Biopsies are also more accurate these days. Men, go ahead and get your PSA test. [1] https://jamanetwork.com/journals/jamaoncology/fullarticle/2594540 https://jamanetwork.com/journals/jamaoncology/fullarticle/25... [2] https://www.cancer.org/cancer/prostate-cancer/about/key-statistics.html https://www.cancer.org/cancer/prostate-cancer/about/key-stat...

sradman 6y ago

Original paper [1]: > Here we report the preliminary results of PanSeer, a noninvasive blood test based on circulating tumor DNA methylation... I’m very surprised that parts of the methylome, the per-cell state-machine that controls what genes are transcribed, have sufficient serum concentration to be detected. I suspect that this approach should work for any diseased cell targeted by the immune system as long as the disease results in a small but unique methylation signature. [1] https://www.nature.com/articles/s41467-020-17316-z https://www.nature.com/articles/s41467-020-17316-z

patall 6y ago
With most of these (cell free DNA) assays, its not a single site that you are measuring but a statistical aggregate about profiles that have been defined for a certain cell type. If you know the overall profile of prostate cells and the profile of normal blood, you can subtract the expected profile from a patient sample and the analyse the left-over fraction for whether it is just noise or is matching to one or multiple known cell types. The surprise from this publication is only that they detect such signatures 4 years earlier than other non-invasive testing. (although nobody in the cfDNA field would be surprised about that).
gww 6y ago
There are newer methods that use antibodies to enrich for methylated dna prior to sequencing [1]. The method increases sensitivity as the majority of plasma cfDNA is unmethylated and hematopoietic in origin. [1] https://www.nature.com/articles/s41586-018-0703-0 https://www.nature.com/articles/s41586-018-0703-0
sradman 6y ago
gww and patall both point out that this is related to cfDNA [1]: > Circulating free DNA (cfDNA) are degraded DNA fragments released to the blood plasma. [1] https://en.wikipedia.org/wiki/Circulating_free_DNA https://en.wikipedia.org/wiki/Circulating_free_DNA

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underdeserver 6y ago

Breakthrough medicinal research is great, but we should always remember that even most promising results - see the COVID vaccines/treatments we've been hearing about over the past few months - end up not viable at the late stages. So, cautious optimism, not great hope and sensationalism, is the right attitude to take here.

qayxc 6y ago
“We are still a ways away from having an accurate blood-based ‘pan-cancer’ screening test. But it is not impossible to achieve,” Pritchard says. I think the article itself got you covered there.

boringcuriosity 6y ago

If this could happen, I would like to envade Mars

kermitje 6y ago

The real false positive rate is much higher than the 5% reported. The false positive rate reported is ~5% in a sample with an equal number of people that did and did not develop cancer, while the ratio in reality is 1/122 (i.e., 1000 people developed cancer, 122000 did not). Could still be a useful development, but it does make me wonder about the cost/benefits at this stage.

deleted 6y ago
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patall 6y ago
Eventually, this is all about cost. cfDNA assays are targetted to in the end cost less than 100 bucks per sample which for the detection of a single cancer puts you in the range of $12000 for one tumor diagnosis. Ideally, you can now decrease the therapy cost of that one diagnosis while also boosting survival chances. And $12000 is not much in tumor therapy. The key however here is the advanced prognosis that may allow totally different therapeutic approaches, extend the understanding risk factors etc. and the fact that you do not need to have a specialist on side, taking a blood sample can in principle be done at home and the rest is automatic. Edit: Oh, and 5% false positives is not that bad actually, I do not have numbers is my head but would expect other essays like breast cancer screening to be also in that range.
- helsinkiandrew 6y ago
  5% false positives on people who have some symptoms of cancer isn’t bad. But 5% of a ‘high risk group’ could be a lot - particularly if the cancer is too early to confirm detection any other way yet and possibly not treatable for several years.
  - minerjoe 6y ago
    They'll find something to sell in this case.
    - 6y ago

billpg 6y ago

We call it the "Do I qualify for health insurance?" test.

civil_engineer 6y ago

If false positive rate is 5%, and 1000 of 123,000 were diagnosed with cancer over 10 years, this test would produce 6,100 false positives, and 1,000 true positives. Six out of seven positive tests would be false positives.

whichquestion 6y ago
Would having 6000 false positives be okay for being able to find the 1000 true positives? Would further testing be able to show whether or not there is actually cancer? Maybe they will be able to improve the accuracy of the test enough where the false positive rate of the test is <<5%...
- TeaDrunk 6y ago
  It also means that the test fails at detecting cancer more often than not, and will mean that if it detects a true cancer this time doctors will be inclined to not take it seriously because evidence/experience is that the test is useless
  - shard 6y ago
    I suppose this takes into account the fact that doctors are humans too, and humans are typically not good at statistics. The probability of cancer from a positive test rises from 0.8% to 14.1%, a significant increase, and seems to warrant a closer look, from a layman's point of view at least.
- mtts 6y ago
  > Would having 6000 false positives be okay for being able to find the 1000 true positives? I’d say no. That’s 5000 people who are told they might have cancer while in fact they don’t and who will then undergo further testing that is at best traumatic and at worst extremely invasive if not outright damaging. Take intestinal cancer, for example. You can get screened for that and if you screen positive, they will take a biopsy - a fairly unpleasant and not entirely risk free procedure. Then it gets worse. If the biopsy shows some part of your intestines isn’t quite in order (a likely outcome, though not necessarily one that indicates cancer) they will take out that bit of intestine, just to be safe. This is a very invasive procedure and because it’s your intestines we’re talking about, you digestive system will be seriously out of whack for a while - if it ever heals completely - seriously and significantly degrading your quality of life. All this for a, let’s use your figures, 1 in 6 chance that you might have had cancer.

cell9840179419 6y ago

Call me silly, but, methylation is a hallmark of aging as well. So all cancer patients would show methylation, but all methylation will not indicate cancer. If that were the case, cancer would be the only cause of natual death.

DangerousPie 6y ago
That's not what the test is doing. They are looking at methylation in specific places.

mchusma 6y ago

A good econ talk on why this kind of thing (improving cancer diagnostics) is by far the most promising "cure for cancer". http://www.econtalk.org/azra-raza-on-the-first-cell/ http://www.econtalk.org/azra-raza-on-the-first-cell/ I hope we have many more tests like this that can be done frequently and add to the arsenal. Great work to these researchers.

ramidarigaz 6y ago
Azra Raza was also on the Mindscape podcast, really realy good interview. https://www.preposterousuniverse.com/podcast/2019/12/16/77-azra-raza-on-the-way-we-should-fight-cancer/ https://www.preposterousuniverse.com/podcast/2019/12/16/77-a...

Cirpop 6y ago

Interesting, especially considering pancreatic cancer. That one can be treated if caught early on, but it hardly ever is, making it incredibly lethal, even for a cancer to be.

TaupeRanger 6y ago

Guess it's time to share this again. "Cancer screening has never been shown to save lives" - Oncologist Vinay Prasad. Detection is not the problem. It's what to do once you find it. Iatrogenic harms are real. https://www.bmj.com/content/352/bmj.h6080 https://www.bmj.com/content/352/bmj.h6080 With better testing, we might be able to save some people, but we might also be subjecting a great deal more people to harms through unnecessary treatment and psychological trauma.

jforman 6y ago
You can't design interventions for problems that you cannot see. Detection alone doesn't save lives, but it is a necessary step to the discovery of interventions that do.
eloff 6y ago
There's a lot to this, if you look hard enough you'll find something wrong. But that something wrong probably would have never progressed into something that kills you - however the interventions you then undergo are not without risk. Like if you have the slow-growing prostate cancer, you'll die of something else. But if you operate you're taking risks of surgery and lifetime incontinence, and might spread it elsewhere in the body. However, I still think early detection is an important first step to finding better interventions. Once you know it's there you can start to come up with less risky/invasive treatments. The odds of dealing with it at an early stage are so much better and the scope of the intervention required so much smaller.

jliptzin 6y ago

Cures and vaccines would be great but I feel like we are missing an opportunity with improved testing not just for cancer but also for infectious diseases. Imagine a toilet that can detect a UTI/STI or parasite or a monitor in my room that can detect airborne viral particles which might tell me I have a cold, flu or COVID before I even know about it. Then I know to treat and isolate before spreading it to others. If we had cheap, instant, accurate tests for infectious diseases then I’d imagine we could begin eradicating some of them.

vondur 6y ago

Seems really cool, but how many cancers progress from something minor to something life threatening? Some of the treatments can be pretty invasive/lot's of side effects. I wonder how much cancer the body can deal with on it's own and never progresses?

rsync 6y ago

If you care even the smallest amount about your own, personal, cancer risk you should immediately cut your feeding window to 8 (or even 6) hours per day and start walking a few miles, daily. I did not mention "fasting" or "diet" or "weight loss". Just condense your caloric input into a tighter window and walk more than zero miles per day. It's silly to pursue fine grained, specific optimizations when the juiciest, lowest hanging fruit is stubbornly, inexplicably, left unpicked.

wonderlg 6y ago
Source? There’s so much information about nutrition online that one should not just trust the first comment found on a forum. Edit: I’m referring to the “feeding window”
- waterhouse 6y ago
  I think the common term is "intermittent fasting" (despite the protest about the word "fasting"), which covers a range of strategies—"time-restricted feeding" is the type where the fasting period is less than a day. https://en.wikipedia.org/wiki/Intermittent_fasting#Types https://en.wikipedia.org/wiki/Intermittent_fasting#Types There is at least some research supporting the claim that time-restricted feeding inhibits the growth of cancer in humans: "In repeated-measures Cox proportional hazards regression models, fasting less than 13 hours per night (lower 2 tertiles of nightly fasting distribution) was associated with an increase in the risk of breast cancer recurrence compared with fasting 13 or more hours per night (hazard ratio, 1.36; 95% CI, 1.05-1.76)." https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4982776/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4982776/ There have also been studies in mice: "Results and Conclusion: TRF had a dramatic effect, reducing tumor growth in obese mice fed a high fat diet (HFD) to levels seen in lean mice. Tumor growth and initiation was also delayed in the transgenic PyMT model of mammary tumorigenesis. Our results further suggest that the antitumor effect of TRF is at least partially mediated by reducing hyperinsulinemia, suggesting that this intervention may be effective in breast cancer prevention and therapy." https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6552025/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6552025/

Balgair 6y ago

To be clear here: these are only circulating cancers. Cancers that break through mesenchymal barriers or can affect the blood are not very common. It's great, amazing even, if you can catch them. But many cancers will never show up in the blood. Still, great work!

skumar88023 6y ago

Very well