Episode 14: Can A Blood Test Really Detect 50+ Cancers?

In this episode, we discuss the viral rise of multi-cancer early detection blood tests (MCEDs) that claim to screen for 50+ cancers with a single blood draw and promise peace of mind (i.e. Galleri & Cancerguard). We unpack why these tests are so compelling, what the marketing gets right (and what it leans on), and what it can feel like to navigate these conversations as patients and as primary care doctors. We also tease the key questions we think matter most—who might consider them, what happens after a “signal detected” result, and why this isn’t a simple yes/no situation in real life. 

00:00 Podcast mission

01:13 Why this topic now

04:43 What these tests promise

05:50 Why it went viral

08:36 Marketing tactics

12:19 Cost and access

14:05 How the test works

18:01 Scary stats vs evidence

19:45 Does it detect cancer

21:04 Sensitivity specificity explained

23:32 Predictive value reality check

25:55 Explaining False Positives

26:41 Why It Cannot Replace Screening

28:12 Pathfinder Study Setup

31:24 Pathfinder Results Breakdown

32:40 Workup Cascade And Harms

36:00 Insurance And Downstream Costs

37:23 NHS Trial Early Signals

40:55 Guidelines And Shared Decisions

44:15 When Doctors Might Use It

49:23 Final Takeaways And Wrap

50:01 Podcast Medical Disclaimer

📖 Read the full episode summary, sources, and resources on our Substack:
 👉www.theantisocialdoctors.com

Transcript

Sonia Singh MD 0:00

You are listening to the Antisocial Doctors Podcast, hosted by me, Sonia Singh, a board certified internal medicine physician with a Master's in nutrition and a special interest in health anxiety

Rebecca Berens MD 0:10

and me, Rebecca Barons, a board certified family medicine physician with a special interest in disordered eating.

Sonia Singh MD 0:16

We're also a millennial women anxious moms and curious humans navigating social media. We've seen firsthand how these platforms can be powerful tools for education and connection, but can also make us unwell.

Rebecca Berens MD 0:28

This podcast is meant to be the antidote to your doom. Scrolling, a solve for the anxiety, stress, guilt, shame, and confusion that comes from social media's messaging around health. In each episode, we discuss a health related talk trending on social media with curiosity, nuance, evidence, humility, and compassion.

Sonia Singh MD 0:45

This is not your average debunking podcast. We wanna explore not just what is trending on social media, but why? Why are so many people drawn to this? What is the nugget of truth here? What are the facts? What can we learn from this as patients and doctors? No shame. No blame, no snark.

Rebecca Berens MD 1:00

We're so glad you're here.

Sonia Singh MD 1:13

Hey Rebecca.

Rebecca Berens MD 1:14

Hey, Sonya.

Sonia Singh MD 1:16

We are recording a second episode in a row, which we have rarely done. So we're on a marathon of talking here. But I'm really excited to talk about this topic 'cause I actually just in the last week, I've had two different patients ask me about this. And so I was like, we gotta get this on the schedule and record it asap. So actually I don't have just one patient story about this topic. I've had several patients ask me about it and I've actually had one or two patients get this testing through other clinics or other providers. And I actually first learned about this particular test through a fellow physician who is advertising it on social media. So it seems like a very appropriate topic to cover. So the topic is blood tests that screen for cancers. I remember when I saw her post about it I immediately googled it and then of course after I Googled it, I started getting a lot of targeted ads everywhere online supporting this. And then I eventually had a rep reach out to me from the company and, wanted to meet with me and wanted to share their studies, quote unquote. And since I do tend to have a lot of patients in my practice with health anxiety. A lot of them are constantly asking me okay, I did this, I did that. What more can I do to make sure that I'm okay? How else can I be proactive? And so the topic of these blood tests for cancer come up a lot. And the last time I had somebody ask about it, I had a very long nuance detailed conversation about that. I shared the data that the rep had given me. And like probably two days later I was driving to my gym and there's an urgent care slash er place that's on the way. And they just had a poster outside that was like, blood test for 50 cancers. Get it done today. And I was like, I wonder if the person in there is having this detailed convers conversation with the patient. But I can see how that. Sign would be very attractive. For sure it seemed like a topic that we should definitely cover here. I'm curious how you first heard about one of these tests and what your thoughts were.

Rebecca Berens MD 3:15

Yeah, I heard about it from a patient actually. They came to me and asked me about the test and, I had never heard of it, so I also Googled it and I was like, let me look more into this because I don't know. And so I did some reading about it and then talked to the patient about what I learned from my reading, and the patient elected to move forward with having the testing done. And so I ordered the test. And so then of course the rep showed up in my office. And since then I've had a couple of other patients who have asked about it and. Some of whom have proceeded after we've discussed it and some of whom have not. But it's not ever one that I have recommended to anyone, but it is one that I am frequently asked about. And I have ordered on occasion when after an informed discussion we mutually decide to move forward with the testing. Yeah. So I have some familiarity with this. And the reports that you get back as well.

Sonia Singh MD 4:05

I always find it a little embarrassing when a patient comes to me with something that I've never heard of and then it's like legit. 'cause then I'm like, man, I should have known about this before they knew about it. I hope this episode, if you have not heard of these blood tests for cancer, I hope this episode and you're a physician or a healthcare provider, I hope this episode allows you to be one step ahead and to have already heard about it and be able to have an informed opinion about it. Unlike you and I.

Rebecca Berens MD 4:30

I think about that every time I see a ad for a new drug and I'm like, what is that drug for? I've never heard of this. Why? Why is it advertised to patients before doctors? That's a topic for a

Sonia Singh MD 4:39

time. I know. It's, I can't even pronounce it. And it's like very embarrassing. I'm like, oh yeah, that one that starts with an R. Okay, so what is the claim about these blood tests for cancer? There's several companies that are doing this. Now again, it's a very rapid area of innovation. So I think we're just gonna see more and more companies that are doing this. The two big ones that people have probably heard about are gallery testing, and then another one that's called Cancer Guard from the makers of Cologuard. Those are the two most popular. We have no affiliation with either of those companies. So what are the claims that are being made about these blood tests? The idea is that you can get screened for 50 or more different cancers with a simple one-time blood test. That this gives you a way to screen for cancers for which there currently is no screening guideline or screening methodology. That it can help detect cancers at earlier stages before they become symptomatic at times when they may be most treatable. And then lastly. It's a way to get ahead of cancer and to give you peace of mind. So those are the claims that are typically made around these products. And I'm gonna go through actually some, I pulled some direct quotes from some of these websites, which I think are really fascinating and I wanna talk about those in more detail. But in terms of why this concept is so viral, I think this is an easy question to answer in a lot of ways. The idea that you can do one simple blood draw and screen for 50 cancers, that sounds amazing compared to you get a colonoscopy at 45 and for that you have to take a day off work to drink this terrible prep, and then you have to go and get this procedure where someone puts a camera in your butt and then you also have to get mammograms every year. Or somebody puts your boob in basically a vice and squeezes it down. Okay. Then you have to wait for results and then the results are like, there's an asymmetry. You probably need more imaging. What does that even mean? Then you have to go back, there's all of that, and then there's go and get a simple blood draw and 50 or more cancers are detected. I think that's very appealing just on its own. As we have talked about on multiple other episodes, I think post pandemic and during the pandemic, everyone just became a lot more aware of their general health and maybe had to face their more. A little bit more. So people, I think there's just been this rise of interest in what can I do to be healthier and how can I get healthier? We've also heard so much in social media and regular media about the rise of cancers in younger patients, certain cancers in younger patients. So many celebrities, it feels like in the past couple of years have died of some devastating cancer that, we wouldn't think of happening in a healthy 45-year-old. And so it's impossible to escape those stories and to not wonder what else can I be doing to not have that happen to me? I also think, as we've talked about in other episodes, that there's this overarching belief developing now that what you get through a doctor or at your doctor's office is just the bare minimum. It's just scratching the surface. The standard screenings are not. Adequate. It's not proactive. We can debate the merits of that particular claim for a long time, I'm sure. But in general, I think faith in traditional medicine and trust in. Doctors as at a, maybe an all time low. I would venture to say

Rebecca Berens MD 7:52

yeah,

Sonia Singh MD 7:53

and even if you do trust your doctor and you do have faith in traditional medicine, it's a hassle and it feels inefficient. And so this idea that you can just get it all checked and taken care of in one day is very attractive. And lastly, as I mentioned, the marketing for it is really good. As somebody who has a couple of businesses and thinks about these things, when I was looking at some of these websites, I was like, this marketing deserves some kind of award 'cause it's so good and so appealing. Even, going into it not being particularly. Pro any of these tests, it was hard to resist some of the marketing that's on there. So actually I have a few quotes that I pulled from the Cancer Guard website. So one of the ones that struck me the most was, your cells have a story, we're listening. Ooh. And it's like your cells have a story, was in small font and we're listening was in really big font. And in the background there's a little sound wave type. Motif going on. And, the way that they describe these tests are that they're detecting a cancer signal. And we'll go into like the whole science and physiology of this in a minute. But so when, they're saying there, it's the cancers, the tumors are sending out these signals and we're detecting those signals. And it's so that phrase is so good and so smart because what they're really picking up on is so many people feel unheard or dismissed or brushed off by their doctor. So when they're asking what else can I do? I'm just really nervous about what this could be or what this pain could be, or do you think, maybe the doctor has told them it's something totally benign, but they're like, but do you think it could be cancer? Is there any way? And so many people have been in that situation and felt gaslit or dismissed. And so this idea of this company's like Nobo, we're listening. We're listening to what your Body is telling us so good. Okay. Then they have a little section that's is cancer guard right for you? You can request the cancer Guard to talk to your doctor if any of the below are true. Number one just says you are proactive about your health. That can be basically anybody. Okay? And we'll go over what the data shows in terms of what populations may benefit from this later on. But remember they're just saying anybody that's proactive about their health you have increased. Risk factors for cancer such as smoking, alcohol, use, obesity, or you're older than 50 you are three years post a cancer diagnosis. That's really more of a, you should probably not be doing this if you are within three years of a cancer diagnosis. Or you have a family history of cancer. I. Family history of cancer is very broad. That many people will say yes to that question. So

Rebecca Berens MD 10:32

yeah, I can't think of anyone who doesn't meet these

Sonia Singh MD 10:34

criteria. You ba they basically positioned it such that it is right for everyone basically. Okay. And then. Another, this is also a direct quote. I thought this was really interesting in telling is they say negative or positive. That's it. Cancer can be intimidating. Understanding your results doesn't have to be no jargon, just clear insight to help you move forward with confidence. So what they're playing on here is so often when you go to the doctor and they say there's a mass, they're like, we don't know what this is. It could be benign. It could be something more. We might have to do additional imaging. We might have to get a biopsy. Anytime you go to the doctor with something it's pretty rare that it's going to be a definitive. Single lab, single imaging result. That's just the entire answer. And that's it. And there's no discussion and there's no questioning. And that's just it. That's just true in medicine. Like it's rare that it's so black and white like that. And the way this test is designed, it will say cancer signal. Cancer signal not detected. And that is it. Even though that's not actually a diagnosis of anything, that is what you are gonna get at the end of this result. And I think they're really playing on people's frustration with getting a mammogram and saying what does indeterminate mass mean? What does a symmetry mean? What does calcification mean? That's the experience that many people are having with their cancer screenings. And this idea that it's just yes or no. It's like a pregnancy test, just yes, no, there's no kind of or in between. Or it might be it's just yes or no.

Rebecca Berens MD 12:04

And even with the pregnancy test, you're like taking a picture and sending it to your friend. You're like, is that a lie?

Sonia Singh MD 12:11

That's why the newer ones are yes or no, or a smiley face.

Rebecca Berens MD 12:15

Yeah, I was too cheap for this.

Sonia Singh MD 12:16

Yeah, you have to splurge on those, Rebecca. Okay. By the way, I should mention the cost of these tests. Let me see. I have it in here somewhere. So the gallery test is $949, and the cancer guard is 6 89. And I don't think either of these at this point, are likely to be covered by insurance just because they're not FDA approved tests and they do not have the data, the evidence behind them at this point to be considered something that is medically necessary. Anyway, so these are quite expensive, typically out of pocket. And I don't think either of these yet are direct to consumer. I do think you have to request the test and some medical professional has to prescribe it or order it for you. So anyway, that's a little bit, and do you have anything to add in terms of why you think this is so popular?

Rebecca Berens MD 13:00

Yeah, no I totally agree with all of that. And I think the, yeah, I hadn't actually seen. This marketing is I've only ever looked at gallery.

Sonia Singh MD 13:09

And so gallery has been out the longest. Yeah. And their website, you can tell, has been scrubbed of any, anything that might look misleading. Like they, I think Oh,

Rebecca Berens MD 13:18

interesting.

Sonia Singh MD 13:19

Their website is very minimal, which makes me think that. They have maybe been burned by making claims on it before. 'cause they say very few things and they have a really big disclaimer. So compared to that cancer guard, which is a lot newer, has a much more robust, like it's quite an experience looking at their website compared to health.

Rebecca Berens MD 13:39

Interesting. I had never even actually heard of Cancer Guard, so I'm really interested to hear, what, if anything, is different about it. But I do remember the first time I looked at the gallery website 'cause I was like, usually a healthy dose of skepticism. Yes. Whenever someone asks me about something that they found on the internet. And I was like, huh, this is not the worst thing in the world, maybe. So we'll talk about that, but

Sonia Singh MD 14:00

Yeah.

Rebecca Berens MD 14:00

But yeah, I'm curious to hear. All of the facts about these,

Sonia Singh MD 14:04

the context and the nuance. Okay. Yeah. So let's get into it. So what are these tests? Actually sometimes in marketing stuff I've heard them referred to as liquid biopsies. I don't know why I just hate that phrase. It just sounds so not medical to me, it makes me think of O Town Liquid Dreams. I'm just picturing that o Town music video from the early aughts when I hear liquid biopsy for some reason. Anyway. So I am not gonna refer to it as that. I am gonna refer to it as an msms E, so a multi cancer early detection blood test. So msms e ds is like the general category of all of these tests. So Cal Gallery and Cancer Guard are the most popular. This is a rapidly evolving technology, so I think we're likely to see more and more of these tests, and they're likely to get more and more advanced. So what we're talking about now here in March of 2026 may not even be, the latest data in March of 2027. So please. Please remember that as you're listening to this. So how do these tests actually work? So all cells, including tumor cells, shed some of their DNA as they're being turned over basically. And so we call that cell-free, DNA, sometimes abbreviated as cf DNA. What these tests are doing are basically looking at methylation patterns on the cell-free DNA that's floating around in your bloodstream. And the methylation pattern is basically a clue as to whether that cell-free DNA. Arose from a tumor and what type of tissue or organ that tumor may have arisen from. So if you're wondering what methylation is, it's basically a epigenetic or biochemical modification that happens to DNA like a little methyl groups gets attached onto the DNA and it alters the gene expression of wherever it's attached. So cancer cells tend to have very bizarre, abnormal methylation patterns and that distinguishes them from regular healthy cells. And then the specific pattern that they have can give clues as to what tissue or site that cell may have originated from. And where there's been a lot of advancement is in AI machine learning models that will now analyze thousands and thousands of regions of DNA and can identify the ones that have specific aberrant patterns and then can predict from those what tissue that may have originated from. So you can use the methylation pattern detection alone, or you can combine that with other technologies like looking for gene mutations in the cell-free DNA, or looking for cell-free RNA or certain proteins or metabolites that are known to be associated with cancers. So you can basically Beef up the screening test by adding a couple other technologies. But the main, the primary methodology is looking for these methylation patterns. So at the end, most of these tests are either gonna report a positive or negative signal. And if the signal is positive, like cancer signal detected, it will also provide you a suspected tissue or organ where they think that tumor. Cell-free DNA may have originated. And, in terms of positive and negative it, there's really just a threshold in terms of how much DNA they, they detect. And so that's, they have a cutoff over which they're calling it positive and under which they're calling it negative. It's not like there is zero in somebody who's negative and one in somebody who's positive. There's like a measurement threshold. So I guess let's put this in a little bit more scientific context. One important fact about the science here is that the amount of cell-free DNA that's shed by a tumor is very proportional and dependent on the overall size of the tumor or the tumor burden. So if you have a really tiny tumor, a very small, tiny tumor, it's going to shed. DDNA. So actually the very tumors that these tests are most interested in picking up, which are like the really early cancers that are not gonna be symptomatic, that are not gonna be picked up with other modalities, are the ones that also shed the least of this DNA that they're trying to detect interest. Okay, so side note here. Now when you go to these websites, I'm already really hating on these websites, but when you go to these websites or when you talk to these reps, something that they lean very heavily on is just general scary stats about cancer. So that is something that I want you to just have your radar up for immediately because. Most of the data they share is actually just about cancer and not really about the tests that they're trying to sell you or convince you to order. So they love to say things like, one out of three patients will be diagnosed with a cancer. They love to say that 70% of cancer deaths happen from cancers that we have no screening guidelines for, they love to say the rates of curing cancer for different stages. That basically the rate for curing a stage one cancer is, or the rate of survival is so much better than stage three or stage four. That's all fine. I don't dispute that those are facts and that they're true. But they say nothing about whether this test is good or helpful or anything like that, and that is 90% of the stuff that they are spewing out on their website, on their social media. When the reps talk to you like this fact about 70% of cancer deaths are happening in for cancers that we have no screening for. They love telling you that when you talk about guideline directed screening, and the reality is that fact does not say anything about whether this test is. Helpful or can reduce those rates or anything like that. Right?

Rebecca Berens MD 19:32

Yeah.

Sonia Singh MD 19:32

So just keep your eyes and ears open for when they're, just flooding you with scary cancer stats as opposed to anything about the how this test performs and its effectiveness or its outcomes. Okay, so moving on. How good are these tests? At detecting cancer. There's a few landmark studies that have looked, that have studied these and most of them are on the gallery test, which has been out and available the longest. So the first big study was the CC GA study, which is circulating cell-free genome Atlas study. It was published in 2001, so it was quite a while ago. And basically it was a perspective case controlled observational validation study. What they were doing in this was they were looking at patients with known cancer and patients with no known cancer and they were trying to see how does our test perform at picking up cases of cancer And, what's the rate of false positives and false negatives. It was a validation study. Okay. And there was actually three sub studies in this whole thing three kind of phases of it. I'm only gonna focus on the clinical validation part of it, 'cause that's what's most relevant for this discussion. But basically the study was Developing the test. And then the last arm of it was invalidating it. So the outcomes they were looking at were sensitivity, specificity of detecting cancer, and then accuracy in terms of predicting the origin of that cancer. So they had a group of people couple thousand people I think, with known cancers, and then they had a group of people with no known cancers. And then they did the ME the gallery test on all of them. There were over 5,000 participants total. So the sensitivity. For detecting cancer, so that means how many of the true cancer cases the test correctly identified as cancer signal detected. Was 51.5%.

Rebecca Berens MD 21:16

Ooh.

Sonia Singh MD 21:16

So yeah not great sensitivity. Okay. Sensitivity was strongly stage dependent, so the sensitivity for stage one cancers was only 16.8%, which is pretty abysmal. The sensitivity for a stage four cancer, which. It's metastasized to a distant location. Like it is quite significant. That was 90.1%. And so it was very dependent on, the stage. It was the best at detecting head and neck, liver and bile and cancers of unknown primary. The unknown primary kinda makes sense to me 'cause I feel like those are the most bizarre.

Rebecca Berens MD 21:49

Yeah.

Sonia Singh MD 21:50

In terms of the way they probably look pathologic or histologically and in terms of the cell, DNA those were the ones that it was best at detecting. The worst that it was at detecting was thyroid, which in the study population there were 14 thyroid cancers and it detected zero of them. Okay. Prostate cancer, it only detected 47 of 420 myeloid neoplasms and then uterine and breast and of note. For breast cancer, the sensitivity was only 30.5%. The sensitivity of mammography for detecting breast cancers is 70 to 90%. So you can see how it compares to our routine, standard screening for that particular cancer. Now specificity for cancer was 99.5%. So what that tells us is that the rate overall of false positives, so of people who are being told you have a cancer signal detected but they actually do not have cancer. The rate of that is very low. But we're gonna talk a little bit more about more nerdy stats stuff in a bit. A bit 'cause there's caveats with that. Okay. So for patients. Without cancer. What the specificity tells us is that it will correctly confirm that they do not have cancer 99.5% of the time. So this suggests a false positive rate of only 0.5%. So I've seen a lot of marketing materials that are like false positive rate less than 1%. So I've seen that advertised. Okay. But there's more to the story, so we'll go on. In terms of accuracy it's pretty decent at figuring out where the cancer signal is from if it picks up the cancer signal. So accuracy of the origin prediction was 88.7%, so it's pretty good at telling you where to look. Now there's two other stats that. I think a lot of people oftentimes, they just look at sensitivity and specificity, and maybe they move on. But the two other ones that are really interesting are the positive predictive value and the negative predictive value. So what the positive predictive value tells you is that for somebody who had a positive result on the test. What is then the likelihood that they are a true case. So for somebody who got cancer signal detected, what is the likelihood that they actually have a cancer? So the positive predictive value for this testing was 44.4%. Okay? So you may be wondering. How can you reconcile the fact that the false positives is less than 1%, but the positive predictive value, like I'm telling you, that if you get a positive signal over half of the time, that is actually not going to be from a cancer. And the answer to that is just like a biostats phenomenon that when the. Thing that you're trying to detect is already an extremely rare entity. It's like a very rare phenomenon. Then even with a very good specificity, sometimes you're going to have, like you, you can have a very bad, positive predictive value and still have a very. Good specificity and a low rate of false negatives. Yeah. And that's really just because the thing that you're measuring happens so infrequently. 'Cause the vast majority of people are gonna get a negative signal or a no cancer signal detected, and that's gonna be correct for them. The negative predictive value. So that means if you got a negative result the likelihood that result is accurate and you do not have cancer is 99.4%. So that's very high. So basically the bottom line here is that it's. Not so great at picking up cancers especially of certain types. If it does detect a signal, it's pretty good at telling you the origin of that signal. But. Even if you get a sign cancer signal detected result, there's an over 50% chance at that point that you do not have a cancer, that you have been falsely told that you have a cancer. But on the whole, when you look at the entire group of people that was screened, that still statistically is a very tiny percentage of people. Does that make sense? Are you, are we following?

Rebecca Berens MD 25:56

I'm following, but this is very hard to communicate to patients.

Sonia Singh MD 26:00

Yes.

Rebecca Berens MD 26:01

When I get to this point, which is why it's such a long conversation,

Sonia Singh MD 26:04

when I get to this point in the conversation, I'm always like. I'm gonna start saying some real nerdy biostat stuff and I don't know if it's gonna make sense, but just try to follow me and let me know if you feel like you're getting this. I have had this talk with people before where, I think most people, I think honestly the specificity and sensitivity are. Sometimes a little harder for people to grasp, but understanding this idea that, okay, if I get a cancer signal detected result over 50% of the time there's actually not a cancer, is I think one of the key facts that I want people to know. Who go into this test or want to get this test. Okay. And also I think that comparison of it only had 30.5% sensitivity for a breast cancer when mammograms have 70 to 90%. I think that's also a good take home fact to hold in the back of your, as a physician to have in your back pocket and as a patient to really be aware of and that this cannot replace or does not substitute for our standard screenings.

Rebecca Berens MD 27:02

Yeah, it's so funny because I remember seeing a. Clinic locally that was advertising this on their website and they talked about a case of a woman whose breast cancer they diagnosed the same day that she came in because she got this test and it's thank goodness we caught this. And my immediate thought was like, I'm quite sure she'd never had a mammogram. That's great. Because it, I think it was like. I can't remember exactly how they word it, but I think it was a fairly advanced breast cancer. And I was just like. I don't know if this is selling the test so much as it is selling, getting a mammogram done, but I didn't know this stat actually about the breast cancer specificity. So that's really even more interesting now. The sensitivity, I think. Sensitivity, yeah. Sorry. Sensitivity.

Sonia Singh MD 27:48

But also, and it, this is very clear on the gallery site, they have a whole disclaimer saying this does not replace your standard screenings. And it does not make any diagnosis that is so important to remind people this does not make a di so that woman technically. She did not get diagnosed with breast cancer, that there was

Rebecca Berens MD 28:03

a lot of things wrong with the way this was framed in this blog post,

Sonia Singh MD 28:07

but yes. Yeah. So anyway yeah. Okay. So let's move on. We'll, and we'll talk about all the caveats and everything, but okay. So the next big study on SEDS was the Pathfinder study. And that was published in The Lancet in 2023. So this was. Perspective cohort study. They enrolled thousands of patients from seven different health systems all over the us. The participants had to be 50 or older, and they were allowed to either have or not have additional risk factors for cancer. So they did not exclude people who were at higher risk, and they did not exclusively do this in patients who are higher risk. Risk factors for higher rates of cancer that they identified or that they were tracking, were. History of smoking cancer predisposition based on NCCN, national Cancer Network guidelines. So that's it has to do with family history and things like that. Heritage, all kinds of other things. Having a hereditary cancer syndrome, having a personal history of cancer that's already had definitive treatment at least three years ago prior to enrollment. So all these participants were given the SA test. And then if a cancer signal was detected, they were further evaluated and worked up by their primary doctor. So there were no, they didn't give them any guidelines of if you get a cancer signal detected, this is an algorithm you follow to evaluate this. The doctor was left to do it at their own discretion. And then they did a review of the electronic medical records 12 months after the test was conducted. And interestingly, their primary objective here was not really outcomes. The primary objective was determine the time to diagnostic resolution following the result of the test. So once the person got a cancer signal detected result, they wanted to see how long does it take from that point to get an answer of yes or no or a diagnosis of cancer for that. Particular patient and what was the extent of testing? What kinds of things were ordered? So I guess this is like a real world use, like what happens when you give people this test and you get results? They did have secondary objectives, which were identifying the positive and negative predictive value, what we just discussed identifying the specificity and then looking at the accuracy of the predicted origin site according to what was ultimately diagnosed in that patient. So the participants were over 6,000 adults over the age of 50. 56% had additional risk factors. So one important note to remember here is if you're already over 50, that comes with some increased risk. So this is not data that we would then generalize to a healthy 30 5-year-old that has no increased risk. Over half of them had some other risk factor that would increase their risk of having a cancer. When you use these populations, you're skewing the numbers in your favor because there's more people that are gonna have something that you can find, right? 90% of these patients were white, which I thought was so interesting because they did it in seven different centers all over the country. So I'm not sure what kind of selection, bias played into that, but the majority of this population was Caucasian. 24.5% had a prior cancer history, which was also interesting. So again, a higher risk population at baseline. And. Working in their favor. This population already seemed very proactive about getting their guideline based screening. So 92% reported being up to date on their colorectal cancer screening. That's probably way more than the general population. 80% reported that they have had recent mammography. So this was a generally proactive bunch that was very plugged in with the healthcare system. So they had a cancer signal detected result in 1.4% of participants. And then the rates were 1.5% in the people who had some risk factor for cancer. And then additional risk factor besides being over 50. And then it was 1.2% in those that did not have additional risk factors. Of those that had the cancer signal detected, 38% were ultimately diagnosed with an actual cancer at the one year follow up mark. Now, could there have been people in whom they could not find it, but maybe there was something? Possibly, but 38% is still even lower than their previous validation study suggested, Their positive predictive value was 44% in that validation study. And according to this, even fewer, which is 38% actually got diagnosed with a cancer. Of those who had no cancer signal detected, 95% remained cancer free at one year. And so then there was only a 1% rate of those people. Within that year being diagnosed with a cancer. And then there was like a three or 4% that were lost to follow up and they did not have a definitive answer about whether they had a cancer or not. Is that again, you could argue that 1% that were diagnosed with cancer at the 12 month mark, maybe they developed the cancer since the time they have a test. So it's not really, it's not telling us.

Rebecca Berens MD 32:38

Yeah.

Sonia Singh MD 32:39

Perfectly. The median time to diagnostic resolution. So the amount of time people lived where they had gotten the result of cancer signal detected to the time they either definitively were told, we do not think you have cancer, or we officially have diagnosed you with a cancer was 79 days. So that's almost two and a half, three months of, workup and waiting basically. True positives, like the ones that did end up having cancer were often resolved earlier. So that was 57 days. So you gotta think okay, for somebody who cancer signals detected, they say, oh, it's in this region. You scan that region, you see it, you biopsy it done. Versus some of these false positives where. There maybe was nothing visible in the places that they identified as the origin and there was nothing to biopsy. I can imagine those took longer. So those took up to 162 days. An average time of 162 days. The false positives most positive patients had additional labs, so the labs that were most commonly ordered following a positive result was C-B-C-C-M-P, which are standard labs that most patients are getting. Blood comprehensive blood counts and comprehensive metabolic panel protein tumor markers, and 92% had imaging. So the vast majority of these patients had some imaging tests done after getting that positive cancer signal result. Most of the time it was either a pet ct, CT or MRI 53% had more than one imaging studies. They have multiple imaging. 49%. So almost half ended up having at least one procedure of some kind, I'm assuming a lot of those were biopsies. And then three of the true positive patients ended up having a surgery following their test result. And one false positive patient ended up having a surgery following their test result. They ended up having an inguinal orchiectomy, so they had a testicle removed because of. Questionable findings on imaging following their cancer signal detected result. So yeah, it went as far as somebody removing a testicle based on wow, the cascade of events that started with this test. That was one patient out of over 6,000. But something to note. Okay. During the 12 months of the study, 122 cancers were diagnosed in the original study population, and only 35 of those were picked up by the SE. The rest of those, so the vast majority were detected via standard screening methods, perhaps incidentally, on another test order for another reason, or based on their clinical symptoms and presentation and the workup that ensued from that. Adverse events related to this test. I was proud that they even reported this, but were four patients, two reported anxiety and bruising at the blood draw itself, and then two reported high levels of anxiety when they were awaiting or receiving their results. The positive,

Rebecca Berens MD 35:22

that's a low number.

Sonia Singh MD 35:23

It's a i that sounds to me like it's very under-reported.

Rebecca Berens MD 35:27

Yeah, that feels underreported. I can't imagine more people were not a little bit anxious.

Sonia Singh MD 35:32

Yeah. Positive predictive value I mentioned was 38% negative. Predictive value was 98.6%. Specificity in this case was 99.1%. So this was really a feasibility study. It was not a study of clinical utility or effects on cancer outcomes or mortality or anything else. Okay. This is just telling us about how the test looked when it was given to a population and what. Kind of diagnostic testing ensued.

Rebecca Berens MD 36:00

Question.

Sonia Singh MD 36:01

Yes.

Rebecca Berens MD 36:01

Who paid for all this stuff?

Sonia Singh MD 36:03

Oh, grail. The company that makes gallery.

Rebecca Berens MD 36:05

Okay. So because in the real world, in the real world, if you're having this test, you would insurance cover it is my question?

Sonia Singh MD 36:13

No.

Rebecca Berens MD 36:14

And so this is the thing that. That I always mention to patients, I'm like I don't know how to get insurance to cover this uhhuh because they didn't cover the initial test. I can try, but

Sonia Singh MD 36:24

oh, you mean to cover the downstream workup?

Rebecca Berens MD 36:26

Yes. The downstream workup.

Sonia Singh MD 36:27

Yes. Okay. That's a great question. I did not think about that, but.

Rebecca Berens MD 36:32

Because that's a, that is an adverse event that we did not talk about. Yes. That,

Sonia Singh MD 36:36

yes.

Rebecca Berens MD 36:36

I'm quite sure people would've been reporting had they been paying out of their own pocket for this, although, I don't know, maybe they were, or maybe their insurance was covering it. I don't know. But

Sonia Singh MD 36:44

no that's such a good point because if someone comes to you and they've got, so you do this test, it says cancer signal detected, it says you've got something in your abdomen or whatever. If you wanna order a CT or an MRI, you have to justify that. And saying they had this test that said cancer signal detected. I don't know. I feel like the authorization people's brain. Yeah. I don't think

Rebecca Berens MD 37:03

The insurance companies are gonna take that. They don't take, they would be, they don't take the normal steps, so

Sonia Singh MD 37:07

Yeah, they don't take the legit reasons. So I think they would just be like, Nope, we've never heard of that. Have a nice day. Okay. Anyway, so that, that is honestly where the published data. Ends. Okay. That's pretty much, that's crazy. Okay. There are several studies that are ongoing right now. There's a Pathfinder two, and then there's a big NHS study on gallery that is not yet published, but that has not stopped the gallery people from trying to disseminate some of the preliminary data. So you actually sent me this 'cause the rep had sent it to you and I have the pdf so I'm gonna link it in the substack, but. Basically there is a gallery study going on right now in England through the National Health Service. So this is the first and only randomized controlled trial on NSAIDs that's happening. They have enrolled 142,000 people between the ages of 50 and 77. They are giving these people the gallery test yearly for three years, and then they're planning to follow for one year after they complete. Three years of testing. The goal is to determine, and this is the point of a lot of controversy, whether using Gall could diagnose more cancers at an earlier stage. So they have very specifically chosen this outcome of can we reduce the number of. Late stage cancers that we diagnose by doing this testing proactively every year. Note, they are not looking at do we change outcomes? Do we decrease mortality? And I think part of the reason they've chosen this. Metric to follow is that real data on outcomes and mortality is going to take decades. And there is clearly demand for this product now. So I feel like they're like, what outcome are we like the most likely to maybe find a positive result for? And can we do the quickest? And so I think they've determined that this might be it. The preliminary data is that while there is a favorable trend towards reduction of stage three and stage four diagnoses towards the end of the trial, there has been no statistically significant reduction in the combined rate of stage three and stage four cancers after screening annually for three years. So basically the thing that they were hoping they would show, they have not been able to show in a statistically significant way. The trial did find that stage four cancer diagnoses decreased at the end of the screening with a greater than 20% reduction in second and third in the second and third years of screening with the gallery test. To me, that's a little bit of data mining. I'm like, okay, that's fine. But that wasn't your primary outcome and you did not achieve, not prove your primary outcome in a statistically significant way. And then they reported on that little PDF of preliminary data. No safety concerns, which I was like, okay, how can I trust anything that you're saying when you think there's absolutely no safety concerns? Did you do that step that they did in the previous trial of looking at anxiety, unnecessary workup, incidental omas and the downstream effects of that? I don't know if they're doing that. It's not in the two page PDF or whatever that, that I have.

Rebecca Berens MD 40:12

What I know of the NHS is they will definitely make sure they know if it costs more or not. So I think. I'm actually really excited to see what the final product of this is. Yeah, because I'm excited that the NHS is doing this study because it I think this will give us real information of what is the real Value of this? Yeah. Yeah, not just financially, but also I think there's the assumption is if we can detect more cancers at stage one and two, they're easier to treat at that stage. So the assumption is that outcome will be. Better for the patient. Of course, like you said, we can't prove that for quite some time.

Sonia Singh MD 40:46

Yes. And the sensitivity of these tests is the worst, for stage one and two cancers.

Rebecca Berens MD 40:51

Yeah.

40:51

Yeah.

Sonia Singh MD 40:51

So it seems like a little bit of a reach, at this point. Yeah. Yeah. So the bottom line is none of these companies or product. Have proven that performing this screening in any population reduces the risk of death from cancer, nor have they determined the optimal population, the optimal timing. Those studies are happening, they're underway, but they're probably gonna take a very long time before we have more of a clear or definitive answer around some of these things. So right now, seds are not part of any society guidelines or recommendations. The American Cancer Society has a little information section and sheet about them, and basically they recommend. Using shared decision making with a medical professional and deciding whether you want to proceed with this test. It doesn't sound, it sounds like they're very excited about the potential of these tests. They've actually funded some laws, supporting funding for them and trying to make them available to more people and accessible. 'cause right now the cost is very prohibitive, but they're, they do not recommend them generally or in any particular patient population. And they just say it should be something that, it's a discussion with your doctor in terms of whether you, pursue this, and their recommendation is that when patients inquire shared decision making should emphasize high specificity, but limited early stage sensitivity. So exactly what we just talked about, the potential for false positives requiring extensive workup, absence of data on mortality and out-of-pocket costs. So I think that's a good summary of a lot of the. Highlights of, what I've just shared. And then they also emphasize that when patients bring it up to you, that is a door opening that is an excellent opportunity to talk to them about evidence-based screenings that already exist. There may be things, intervention, screenings that patients just don't realize they could be doing. So if they are just feeling anxious about their cancer risk or wanna know ways that they can reduce that, this is an opportunity to talk to them about some of those things. Anything you wanna add to that?

Rebecca Berens MD 42:48

Yeah, no, I think that is the shared decision making conversation that we have also. I think the other thing that often comes up when we have these conversations is if it's based on family history that they're concerned. Sometimes it is an opening to talk about do you qualify for genetic testing for a cancer syndrome? Yeah, absolute. Absolutely. Because I think that's something that, that, that would potentially change the screening guidelines for that patient. And is often. Missed. There's so many things PCPs are supposed to be doing now in their visits. Yes.

Sonia Singh MD 43:16

Yes,

Rebecca Berens MD 43:17

it's really hard to keep track of all these things There are other potential options that have more evidence behind them that potentially could be beneficial for patients who are concerned based on their family history?

Sonia Singh MD 43:26

No, a hundred percent, yes. And I feel like one that I recently have tried to get better about screening for is, if women have, just based on. History factors greater than 20% lifetime risk of cancer, they may qualify for additional breast cancer screening and or genetic testing. Yeah. Even with negative genetic testing, they might qualify for higher screening. Yeah. And so I think there's a lot of these little things that people don't realize, or even. Things they have the option to do. And if sadly as the PCP, I will admit that sometimes if they don't bring it up to me, sometimes those things get missed, in just the standard process of doing a physical sometimes that that, that is not front and center. And so bringing that to your doctor's attention and telling them that you're concerned about and reviewing that family history is a great pla a great opportunity to advocate for yourself.

Rebecca Berens MD 44:13

Yeah. Yeah.

Sonia Singh MD 44:15

Okay, so what can we learn from this as patients and doctors? I think as a doctor this technology and the availability of this testing I think is really interesting and I'm glad that I had the opportunity to learn more about it and read more about it. I think it has a lot of potential. It's not just. Scam. I think there's a lot of doctors who if they haven't heard about something in any sort of official guideline or from any medical source and they hear it from a patient, they're automatically like, oh, that's mombo jumbo. There's no blood test for cancer, and this is, that is, that's not true in this case. I think this is a pretty legitimate technology and it's rapidly evolving and it's actively being studied, there may be data to support its use very soon, but right now it doesn't seem like it's fully there. So I don't think there's enough data to recommend it broadly. I certainly would not send out a blast to my practice and be like, Hey guys, like I'm offering gallery testing. Anybody want it?

Rebecca Berens MD 45:07

You wanna put a billboard on outside your clinic?

Sonia Singh MD 45:09

No, we not Hang up the sign. No. But I do think that there's definitely some potential clinical utility and I can think of a few specific clinical scenarios where if the suspicion of cancer for some reason is high having it be part of the conversation I think is reasonable. I've had one or two patients that I've brought it up to when we've been. A discussion about this. In most of those cases there was some conventional medical option of what would be the next step, but sometimes it was laparoscopy or CT with radiation or something that involved risk. And so I thought maybe I should talk to 'em about this option because I should respect their. And this exists. And if they prefer to try this, having fully informed consent going into it, then no, this wouldn't be unreasonable. I wouldn't be opposed to ordering it. I have a patient who's Ashkenazi has a lot of cancer history in her family. I've already done the genetic testing. It was all negative. But when she turns 50, if she wants this, I would probably be open to it. Just 'cause I think again, the pre, when you raise the pretest probability of something that the test becomes a lot better. So if you're already highly suspicious for some reason, I think you and I both sometimes I have a spidey sense where I'm like, yeah, I can't justify this to the insurance company. And I, there's no algorithm that I can follow, but I. Feel as though something is happening with you that I cannot put my finger on. And so I think for those cases, it's not unreasonable to have a conversation with a patient about it.

Rebecca Berens MD 46:32

Yeah, and again, like I said, this is something that I've never recommended it to a patient, but it's been patients have asked me about it several times and I have ordered it a handful of times. I have a few patients who own companies and they are like, I need to be on, I need to know what's going on with me because my company will. Self-destructive, I disappear. Which again, there's a lot of anxiety there, but really they just wanna know that they're okay and obviously this doesn't prove that you're okay. But there still could be false negatives. There could be false positives. There are PBP costs. But for those patients, after discussing all of those limitations and risks and, they still wanted to proceed with the test. And I think that's the thing is if you have the resources and fully understand what you're getting yourself into. I think it is very reasonable to proceed with something like this, but. It's not something that I would be recommending in most clinical scenarios at this point with the data we currently have.

Sonia Singh MD 47:27

Yeah. Yeah, I totally agree. I feel like I have a lot of patients who come back to this idea of I wanna feel that I did everything I could, that I wanna feel that I did everything that was available and. If I go into it understanding that, okay. Half the time, actually, I think it's just I really emphasize this okay, if this thing comes back and it says cancer signal detected, we are not gonna panic. Yes. We are not gonna, start writing our last will and testament and giving away all of our. Things we are going to remember that even in the studies of this, which were in different populations than probably what a lot of these patients are, even then, more than half the time it was not akin I think as long as they go into it with that understanding and with the guidance of a qualified medical professional and they're already up to date on all of the routine, age appropriate, recommended screenings that exist. Then I think it is not unreasonable for that PA and they have the resources. They have the resources and it's not like they're foregoing something else that would be really be beneficial to them health wise in order to pay for this thousand dollars blanket.

Rebecca Berens MD 48:31

Yeah, because similar to our full body MRI episode, like I could see a world in which someone's I can't afford health insurance, but I'll just go get these, this scan and this blood test, and then I'll be good. No.

Sonia Singh MD 48:42

Yes. If you think about the amount of time, money, effort, hassle that goes into getting a mammogram, getting a colonoscopy, getting your pap smear, all of it sucks. Like it's all bad.

Rebecca Berens MD 48:52

It's very unpleasant.

Sonia Singh MD 48:54

It's very unpleasant. It's a pain. You have to miss days of work. It's not fun. It's physically unpleasant, and so I think. This idea of this simple blood test is so appealing, we really have to emphasize over and over, it is not a replacement for any of those things. And it should not be used that way. You should not be like I had a no cancer signal detected, so I'm not gonna rush on getting my mammogram and I'm not, I'm gonna wait a few years before I get my colonoscopy. You cannot rely on it from that, in that way, based on the data that we have so far.

Rebecca Berens MD 49:21

Yeah.

Sonia Singh MD 49:22

Okay. I think that brings us to the end of the episode. I am gonna put all the references, including all of those kind of landmark studies in the Substack post for this. I'm also gonna put a link to the page from the American Cancer Society for patients on this topic, which hopefully will be a helpful resource for physicians who are looking for a quick and easy thing to send people who may not wanna listen to our. 45 minute conversation on this topic. And I will also link that PDF that you were given by the rep. That is the talking points for healthcare providers around the NHS data that's coming up. So

Rebecca Berens MD 49:56

that's

Sonia Singh MD 49:56

it. Thanks Rebecca.

Rebecca Berens MD 49:57

Thanks Nia.

Sonia Singh MD 50:00

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