These tests on the other hand detect circulating tumor DNA (ctDNA), among other things. It is well known that tumors shed DNA and other material more than normal cells, even at early cancer stage. (Of course, later stage and more aggressive tumors are more indeed likely to shed more.) The detection limit for some of these tests is in the range of single digit copies of DNA fragment per mL of plasma.
Furthermore, the goal isn’t necessarily to detect every cancer as small as it could possibly be. Even if you don’t do a great job at finding all cancers at stage I, you may still save lives by detecting cancers at an earlier stage than they otherwise would have been found. Finding something at stage II instead of III or stage III instead of IV may well mean the difference of a shot for curative resection / radiation. (Whether these tests would be remotely cost-effective at attempting this at population scale... I leave as an exercise to the reader & healthcare system.)
Grail had a paper with some scant info on their test performance in multiple cancer types across all cancer stages. https://www.annalsofoncology.org/article/S0923-7534(21)02046...
No, I'm very clear on ctDNA, cell-free DNA, whatever you want to call it.
My point stands: early detection goes back to in situ lesions.
The first problem is finding in situ lesions, which is hard.
The second problem is the amount of fear-induced care this generates. These tests are screening tests, so the vendors will lower their operating points to get their false-negative rates down, which will drive up fear, which will drive up follow-on testing, which will drive up follow-on treatment. How much is what matters.
US healthcare costs are already astronomical to the point of becoming a national security problem. And you want to spend more?
> They won't work for in situ tumors, almost by definition.
Which isn't true. The studies from multiple companies' tests demonstrate that they _can_ detect in situ tumors. Not always super duper well, and not always for every single cancer type, but still.
Whether this is a good idea / cost-effective is another question, and certainly a big deal as you point out.
At first diagnosis, the doctors told him to go home.
He later got a call from a doctor who said he would operate. He then called back and said he couldn't. I imagine the hospital looked at the tests, and found it traveled to far, and disallowed the Wonderboy doctor to waste money.
The Wonderboy doctor called back and said sorry. I would have been nice if the doc didn't drag him into office visits, and give him sanctimonious speechs on alcoholism though. This was a good hospital in the Bay Area.
My point is if this study pans out, he probally would still be around?
(If you have money. Get a full body scan. And no they don't pick up on small tumors, but are better than nothing.)
We should also remember that the assays are improving all the time.
Having said all this, early detection is not prevention, and the endgame still remains prevention I think.
This whole field also serves as further confirmation that everything intestesting was discovered in the life sciences in the 1970s [1].
This is true, but you have to not have too many false positives.
A friend of mine went to get her mammogram, and it saw "something". She was a mess until the biopsy came back negative. "Mess" meaning high blood pressure, palpitations, etc.--that false positive could very well have killed her with a cardiac event. A screening test like this that has even worse false positives will kill some people like her.
Another one has always had negative mammograms and extensive 3D imaging. Suddenly, her breast blew up to twice its size. Everyone assumed it was a localized infection because she just had a negative mammogram set less than 30 days earlier. The only reason they bothered to order a biopsy was to try to break whatever lymph clog was causing her "edema". Oops--Stage 3 invasive lobular breast cancer throughout the entire breast.
You can't see lobular breast cancers on mammograms because they never form a lump, they just inflitrate all throughout the normal cells. They're about 30% of all breast cancers and a screening test that can flag these (even with a false positive) would be a godsend. Being able to flag people for a followup MRI would be a significant improvement if it doesn't have too many false positives. A screening test like this would be quite beneficial.
As always in medicine, things are complicated.
Are some types of cancer better treated like HIV/AIDS where it's simply managed.
https://www.cancer.org/healthy/cancer-causes/general-info/li...
You can see a breakout at the bottom of this poster [1] from Grail (developing a methylation based liquid biopsy) showing sensitivity per-cancer and per-stage.
Sensitivity increases as stage increases, as expected, and cancers like Leukemia are well detected. IIRC, the stage classifications vary across different tissue types as to when the cancer breaks through the basement membrane - would be compelling if sensitivity of the assay rises in accordance.
[1] https://grail.com/wp-content/uploads/2020/12/ASCO_2019_CCGA2...
Don't assume your gut feeling correlates with reality in such a quantitative problem. There might be low hanging fruit here - and it might save your freakin life man! Biochemical testing is not intuitive and the details are best lead to quantitative biochemists and such. Heck, even what Theranos embarked on doing could've lead to breakthrough improvements for some tests if they had been honest and focused the money on the research avenues that could've produced results...
The problem with this kind of screening is even tests that are highly accurate in a population with a high incidence rate are super duper inaccurate when used against the general population. False positives often have significant consequences, including invasive tests and surgeries with their own risks. tl;dr Bayes' rule is a bitch. [2, 3] I doubt they've solved this problem - but I sure hope they have because why wouldn't I?!
> "A patient goes to see a doctor. The doctor performs a test with 99 percent reliability--that is, 99 percent of people who are sick test positive and 99 percent of the healthy people test negative. The doctor knows that only 1 percent of the people in the country are sick. Now the question is: if the patient tests positive, what are the chances the patient is sick? - The intuitive answer is 99 percent, but the correct answer is 50 percent...." [3]
[1] https://www.nhs.uk/conditions/prostate-cancer/should-i-have-...
[2] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7082531/
[3] https://sphweb.bumc.bu.edu/otlt/mph-modules/bs/bs704_probabi...
This test would be a fear driven profit center for these companies. I don’t like them at all. Easy way to sell the test isn’t it? “You don’t want cancer do you?”
My father was diagnosed with pancreatic cancer. The doctors gave him six months to live. They said “if she goes on chemo will get a year”. Both myself and my sister-in-law who is in oncology nurse advised him not to go on chemo. But he did. He died a month after starting chemo because it caused his bile duct to clog and it shut down his liver.
Yeah, so doing nothing, that’s my motto.
Science can be a breakthrough and really interesting and yet still no practical for use in medicine.
A really good example was Pfizer's inhaleable insulin. I mean, I don't need some MBA to tell me it's better than sticking yourself with a needle! Turns out it was a wildly impractical solution looking for a problem that doesn't exist.
Same thing with cancer diagnostics. Unless you can draw a line all the way from diagnostic use to results to improved outcomes, it's just data.
Pfizer’s inhaled insulin was approved by the FDA.
But nobody wanted to use it because it didn’t solve a real problem.
> Unless you can draw a line all the way from diagnostic use to results to improved outcomes, it's just data.
This is why we do trials, to figure out if we can draw a straight line from results (pre-clinical) to outcomes (clinical). This is the question that the cancer diagnostic trial will hopefully answer - can we improve outcomes using these diagnostics?
I don't completely see the relevance of your story about inhaled insulin. As far as I can tell it was not better than standard of care in a meaningful way, whereas with this trial there really isn't a standard of care to speak of, and this is going to be the largest such trial to date. Plenty of drugs fail to make an impact in the market, for a variety of reasons, which can't always be predicted ahead of time.
Elsewhere you write that this is not going to provide actionable information. I largely agree with this statement - as of today. I also think that this trial will provide valuable information about the landscape of cancer diagnostics in general, information which may be increasingly relevant in the future and may turn out to be actionable. This is the most relevant quote from the source article that speaks to why they are doing this:
> Q: Given the doubts, why proceed? > A: The exciting thing is, we don’t have screening tests for the lethal cancers like pancreas and ovarian. We’re desperate. But we have to put our emotions aside and do our due diligence to evaluate these technologies and be able to speak with confidence about what this can and can’t do.
For 75 million dollars, the cost of a year of maintenance for a handful of fighter jets, I think it's worth it, and I'd much rather have the NCI running this than a private company. If this trial completely falls on its face and public money keeps being expended in this direction, then I would certainly revisit my opinion about the worthiness of trials of this nature.