
Experimental blood test detects cancer up to four years before symptoms appear - prawn
https://www.scientificamerican.com/article/experimental-blood-test-detects-cancer-up-to-four-years-before-symptoms-appear/
======
kermitje
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.

~~~
patall
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
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.

~~~
refurb
But in this example - stomach cancer - you could just skip the test and do a
routine endoscopy and get some tissue samples. You’d have a much higher
confidence in the result.

Reminds me a bit of the PSA test for prostate cancer. More of an early
warning, but with the weak predictability, doctors are moving away from
routine PSA tests.

~~~
jjk166
If option A is regular blood tests with an endoscopy to confirm should the
blood test come back positive and option B is getting endoscopies on a regular
basis, option A is a no brainer. While it might not be super invasive, I'd
definitely like to keep the number of times a tube has to be shoved down my
throat to a minimum.

~~~
refurb
But if the false positive rate is high, just skip the test and do the
endoscopy.

~~~
jjk166
No, the false positive rate is irrelevant. Let's say you want to check for
cancer annually and the blood test has a 50% false positive rate:

If you only get endoscopies after positive results, you get an endoscopy every
other year. If you skip the test and go straight to the endoscopy, you get one
every year. Thus you get half as many tubes shoved down your throat if you get
the blood test.

For a more reasonable false positive rate like 5%, you would have a 50/50
chance of getting a false positive any given decade. I'd much rather get 4
endoscopies than 40.

Indeed, for any false positive rate less than 100% (which isn't really a test
to begin with) still on average decreases the number of endoscopies you need.

Really the metric that's important is the false negatives: if that's too high
then I can't safely forego the endoscopy just because this year's blood test
was negative. Even then though, if the blood test has a long lead time then
maybe it's safe to wait and see how next year's blood test goes.

------
mchusma
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
Azra Raza was also on the Mindscape podcast, really realy good interview.

[https://www.preposterousuniverse.com/podcast/2019/12/16/77-a...](https://www.preposterousuniverse.com/podcast/2019/12/16/77-azra-
raza-on-the-way-we-should-fight-cancer/)

------
scandox
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.

~~~
thaumasiotes
> 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".

~~~
endymi0n
I've heard it phrased by a doctor as "Almost every man dies WITH prostate
cancer. Almost no man dies FROM prostate cancer."

~~~
tonyedgecombe
Anecdotal but both of my grandfathers died from it, one at age 52.

~~~
yread
10 year survival rate of prostate cancer is 98%.

[https://www.cancer.net/cancer-types/prostate-
cancer/statisti...](https://www.cancer.net/cancer-types/prostate-
cancer/statistics#:~:text=The) 5-year survival rate for most men with
local,prostate cancer combined is 98%25.

~~~
abalone
Note: That’s if it’s detected.

------
civil_engineer
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
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%...

~~~
mtts
> 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.

~~~
ethbro
You're leaving out all choices in your decision pipeline.

If you screen positive, you can elect to have a biopsy or scan.

If your results come back inconclusive, you can elect to pursue surgical (or
other) intervention.

That's what medicine is: a selection from among potential procedures, given
the information at hand, informed by previous outcomes in similar or
applicable situations.

In this case, we simply have more information. If said information turns out
to have limited predictive power on the ultimate occurance of cancer, that
will be incorporated into detection and treatment practices.

But the important thing is having _more_ information than we had before.

~~~
vharuck
If the patient were a robot, this would make sense. But people are easily
scared, especially by the word "cancer," and fright can lead to bad decisions.
And this is a decision that's made by individuals, including the doctors, who
just want to take the "safe" option.

For example, the United States Preventative Services Task Force, which
effectively decides the preventative procedures covered by Medicare and
Medicaid, recommended against routine prostate specific antigen testing for
prostate cancer in 2012. They backed that up with data on mortality and
unnecessary procedures. Prostate doctors around the country flipped out. The
doctors are focused on helping their individual patients. That's good, but it
keeps them from seeing the overall harm to the entire population.

------
sradman
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
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).

------
TaupeRanger
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
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.

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

------
rsync
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
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
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/)

------
vondur
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?

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Cirpop
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.

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Balgair
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!

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cell9840179419
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
That's not what the test is doing. They are looking at methylation in specific
places.

------
jliptzin
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.

------
underdeserver
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

      “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.

