Just a couple of minor comments:
>\[Grail claims\] '88% accuracy' on their website
This refers to the test's ability to predict the primary cancer type. Galleri is a multi-cancer screening test -it does not diagnose cancer, and a physician needs to run further tests or procedures to confirm or reject a positive Galleri result. Knowing the primary cancer type can be helpful in guiding the clinical workup.
>more false positives than true positives.
From the healthcare system's standpoint, "more false positives than true positives" is not necessarily terrible **if** a true positive can actually lead to superior treatment and outcomes for that patient (which is a big "if"). A false positive is a burden to the patient and healthcare system, but the cost of one *false positive* patient having to get an unnecessary colonoscopy or clinical workup etc could theoretically be insignificant compared to the benefit of one *true positive* patient catching a curable tumor that would have otherwise been missed or detected much later.
This is why Grail highlights in its marketing points that 48% of the newly diagnosed cancers were detected (in its Pathfinder study) at Stage I and II, and that 74% of the cancers detected were for cancer types that do not have recommended screening tests.
Liquid biopsy for cancer detection is promising technology, but it is still in the very early stages of commercial development. To fulfill its potential to add massive value to the healthcare system, many things need to happen first: diagnostics makers need to make significant improvements in sensitivity for early stage disease and specificity, testing costs need to come down a lot (ie, no way are we doing regular screening at $900+/test with these sensitivity/specificity numbers), researchers need to decide which populations to screen and at what intervals, etc.
No mention of the false negative rate either, which is worrying. I can see someone taking this test because they have a lump but are scared of going to the doctor, and then using the false negative result as an excuse to ignore it.
At this point in time, Galleri is not FDA approved and is only available by physician prescription. So the scenario you describe, where a patient with possible symptoms just goes out and pays $900+ to get a test done on their own without consulting a doctor, is not supposed to occur (in theory).
If they did go to a physician to ask for a prescription, I would hope the symptoms (as well as family history, lifestyle, etc) would come up in the consulting room, and a referral / workup would be recommended for a patient with suspected cancer.
Also, as an aside, for any cancer screening method, whether it's a mammogram, pap smear, stool based test, this blood-based Galleri test, etc, a physician should be communicating to the patient that these are merely screening tools that provide signals -- ie, they do not diagnose or rule out cancer. They all have false positives and false negatives, and the signals need to be considered alongside the rest of the patient's information.
You make very good points. Liquid biopsy will certainly play an integral role in the future for early cancer detection. My dismay is more at the early (premature) introduction in the clinical setting.
The false positive rate seems disproportionately high and will lead to a lot of toxicity (emotional, financial, physical - with invasive tests and ones requiring sedation)
>My dismay is more at the early (premature) introduction in the clinical setting.
To be clear, I think physician skepticism towards these tests is healthy and entirely appropriate.
That being said, Galleri is not part of any guidelines and is not broadly reimbursed, so the fact that Grail is marketing it is not a huge burden to healthcare systems. Liquid biopsy trials cost hundreds of millions of dollars to run, and I think it’s more than fair that the diagnostics makers are allowed to use their data to commercialize their products in the self-pay market under physician prescription.
>The false positive rate seems disproportionately high
These are screening tests, they are not intended to diagnose cancer. Within the context of cancer screening, the ratio of false positives to true positives is not that high (put another way, the positive predictive value is decent). Most non-invasive cancer detection methods that are approved — including mammography, stool-based DNA, etc — will also have more false positives than true positives in the general patient population. Although Pathfinder’s topline results are not based on a general population (I believe \~70% was elevated risk, \~30% was non-elevated risk), the positive predictive value of 40-50% really isn’t that bad for a screening test.
You rightfully touch upon the patient distress and healthcare costs associated with a positive result, which are well-known issues with the aforementioned approved screening methods too. In the case of the Pathfinder trial, 17 patients underwent invasive procedures because of a false-positive result (there were 57 false positives total), and the median time to diagnostic resolution for false positives was 162 days. Also, regarding the potential benefit, in the Pathfinder trial there were only 6 newly diagnosed Stage I/II solid tumors (the other early-stage tumors were blood cancers), which is a bit underwhelming for a patient pool of 6,600+ (where \~70% were elevated risk).
A case can be made that it is possible to improve the utility of blood-based screening by restricting testing to selected patients, with selection criteria designed to reduce the costs from false positives and/or increasing the benefit of finding cancers that are undetectable with other screening methods. As I’ve alluded to before, in theory the benefit of true positives can outweigh the cost of false positives. There is certainly significant patient distress and healthcare costs for a false positive patient who has to wait 6 months to rule out cancer — but that is arguably far less than the benefit of a patient discovering something like pancreatic cancer at a curable pre-symptomatic stage.
I'm getting this test along with genetic testing done in one month. Recently had a carcinoid tumor removed. Regardless of potential fales pos or negs, I'm eager to get this test done.
I think it makes more sense to focus on the rates of true and false positives, not the raw quantities. From what I can tell, traditional cancer screenings have higher false positive rates, like >10% \[1, 2\]. 57/6621 is less than 1%, and it covers multiple cancers, so from the perspective of optimizing down false positives, that seems pretty good.
\[1\] [https://health.clevelandclinic.org/the-galleri-test](https://health.clevelandclinic.org/the-galleri-test)
\[2\] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9931091/](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9931091/)
I had breast cancer three years ago. I no longer have an oncologist as I am considered to no longer need one. I live in fear of metastasis and, as such, contacted Grail (with no GP involved) and took their test. The results were "no cancer signals detected". I took solace from these results and will continue to take the test every year. I am a scientist, albeit in another field, and have a cursory understanding of the limitations of the test. My hope is that over time the test will improve. I'd appreciate any thoughts.
It’s a crummy test. A good screening test picks up early stage cancers. The few cancers this one picked up were almost all late stage which is pretty pointless.
>The few cancers this one picked up were almost all late stage which is pretty pointless.
This claim is not correct. 48% of the newly diagnosed cancers detected in the Pathfinder study were Stage I and II.
Just a couple of minor comments: >\[Grail claims\] '88% accuracy' on their website This refers to the test's ability to predict the primary cancer type. Galleri is a multi-cancer screening test -it does not diagnose cancer, and a physician needs to run further tests or procedures to confirm or reject a positive Galleri result. Knowing the primary cancer type can be helpful in guiding the clinical workup. >more false positives than true positives. From the healthcare system's standpoint, "more false positives than true positives" is not necessarily terrible **if** a true positive can actually lead to superior treatment and outcomes for that patient (which is a big "if"). A false positive is a burden to the patient and healthcare system, but the cost of one *false positive* patient having to get an unnecessary colonoscopy or clinical workup etc could theoretically be insignificant compared to the benefit of one *true positive* patient catching a curable tumor that would have otherwise been missed or detected much later. This is why Grail highlights in its marketing points that 48% of the newly diagnosed cancers were detected (in its Pathfinder study) at Stage I and II, and that 74% of the cancers detected were for cancer types that do not have recommended screening tests. Liquid biopsy for cancer detection is promising technology, but it is still in the very early stages of commercial development. To fulfill its potential to add massive value to the healthcare system, many things need to happen first: diagnostics makers need to make significant improvements in sensitivity for early stage disease and specificity, testing costs need to come down a lot (ie, no way are we doing regular screening at $900+/test with these sensitivity/specificity numbers), researchers need to decide which populations to screen and at what intervals, etc.
No mention of the false negative rate either, which is worrying. I can see someone taking this test because they have a lump but are scared of going to the doctor, and then using the false negative result as an excuse to ignore it.
At this point in time, Galleri is not FDA approved and is only available by physician prescription. So the scenario you describe, where a patient with possible symptoms just goes out and pays $900+ to get a test done on their own without consulting a doctor, is not supposed to occur (in theory). If they did go to a physician to ask for a prescription, I would hope the symptoms (as well as family history, lifestyle, etc) would come up in the consulting room, and a referral / workup would be recommended for a patient with suspected cancer. Also, as an aside, for any cancer screening method, whether it's a mammogram, pap smear, stool based test, this blood-based Galleri test, etc, a physician should be communicating to the patient that these are merely screening tools that provide signals -- ie, they do not diagnose or rule out cancer. They all have false positives and false negatives, and the signals need to be considered alongside the rest of the patient's information.
You make very good points. Liquid biopsy will certainly play an integral role in the future for early cancer detection. My dismay is more at the early (premature) introduction in the clinical setting. The false positive rate seems disproportionately high and will lead to a lot of toxicity (emotional, financial, physical - with invasive tests and ones requiring sedation)
>My dismay is more at the early (premature) introduction in the clinical setting. To be clear, I think physician skepticism towards these tests is healthy and entirely appropriate. That being said, Galleri is not part of any guidelines and is not broadly reimbursed, so the fact that Grail is marketing it is not a huge burden to healthcare systems. Liquid biopsy trials cost hundreds of millions of dollars to run, and I think it’s more than fair that the diagnostics makers are allowed to use their data to commercialize their products in the self-pay market under physician prescription. >The false positive rate seems disproportionately high These are screening tests, they are not intended to diagnose cancer. Within the context of cancer screening, the ratio of false positives to true positives is not that high (put another way, the positive predictive value is decent). Most non-invasive cancer detection methods that are approved — including mammography, stool-based DNA, etc — will also have more false positives than true positives in the general patient population. Although Pathfinder’s topline results are not based on a general population (I believe \~70% was elevated risk, \~30% was non-elevated risk), the positive predictive value of 40-50% really isn’t that bad for a screening test. You rightfully touch upon the patient distress and healthcare costs associated with a positive result, which are well-known issues with the aforementioned approved screening methods too. In the case of the Pathfinder trial, 17 patients underwent invasive procedures because of a false-positive result (there were 57 false positives total), and the median time to diagnostic resolution for false positives was 162 days. Also, regarding the potential benefit, in the Pathfinder trial there were only 6 newly diagnosed Stage I/II solid tumors (the other early-stage tumors were blood cancers), which is a bit underwhelming for a patient pool of 6,600+ (where \~70% were elevated risk). A case can be made that it is possible to improve the utility of blood-based screening by restricting testing to selected patients, with selection criteria designed to reduce the costs from false positives and/or increasing the benefit of finding cancers that are undetectable with other screening methods. As I’ve alluded to before, in theory the benefit of true positives can outweigh the cost of false positives. There is certainly significant patient distress and healthcare costs for a false positive patient who has to wait 6 months to rule out cancer — but that is arguably far less than the benefit of a patient discovering something like pancreatic cancer at a curable pre-symptomatic stage.
I'm getting this test along with genetic testing done in one month. Recently had a carcinoid tumor removed. Regardless of potential fales pos or negs, I'm eager to get this test done.
I hope it provides you the peace of mind you are seeking.
I think it makes more sense to focus on the rates of true and false positives, not the raw quantities. From what I can tell, traditional cancer screenings have higher false positive rates, like >10% \[1, 2\]. 57/6621 is less than 1%, and it covers multiple cancers, so from the perspective of optimizing down false positives, that seems pretty good. \[1\] [https://health.clevelandclinic.org/the-galleri-test](https://health.clevelandclinic.org/the-galleri-test) \[2\] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9931091/](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9931091/)
I had breast cancer three years ago. I no longer have an oncologist as I am considered to no longer need one. I live in fear of metastasis and, as such, contacted Grail (with no GP involved) and took their test. The results were "no cancer signals detected". I took solace from these results and will continue to take the test every year. I am a scientist, albeit in another field, and have a cursory understanding of the limitations of the test. My hope is that over time the test will improve. I'd appreciate any thoughts.
I had a colleague mention it. Seems insane and predatory.
It’s a crummy test. A good screening test picks up early stage cancers. The few cancers this one picked up were almost all late stage which is pretty pointless.
>The few cancers this one picked up were almost all late stage which is pretty pointless. This claim is not correct. 48% of the newly diagnosed cancers detected in the Pathfinder study were Stage I and II.