Early Detection, Part 1: Finding Cancer in the Blood, Years Before Symptoms

Chuck: Welcome to the Good News About Cancer. I'm Dr. Chuck Ryan.

In each episode of this show, we talk to one of our colleagues about a promising development in cancer. We'll break down what's new, why it matters, and how it points the way forward.

Nick: The earlier we can detect cancers, the better the chances to provide either surgeries or therapies with intent to cure. So it was a basic question in the field. There wasn't any organized study to address, ‘Well, how early can we detect them?’ So that's what we tried to do.

Chuck: For a long time, the way cancers were detected was that they began causing symptoms, and a person went to their doctor and received a diagnosis as part of a workup for those symptoms

Many other cancers are detected when a patient does not have symptoms, but they undergo a specific screening test that could be a mammogram, or a pap smear, or PSA tests for prostate cancer.

Now, these are all very good examples of early detection of cancer. This kind of technology has allowed us to save many, many lives over the years and improve the outcomes for those patients who are diagnosed with those diseases. But there's more work to be done to advance early detection so that more cancers – multiple cancers – can be caught as early as possible.

And in fact, for as much as we talk about the importance of colonoscopies and mammograms in those tests, many cancers – in fact, perhaps even most cancers – do not have a means of early detection.

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So today on the show, we're going to hear a conversation. My co-host, Dr. Alicia Morgans, and I had with Dr. Nick Papadopoulos, a professor of oncology, pathology and human genetics at the Johns Hopkins University School of Medicine.

He's one of the many researchers working to understand how blood tests can detect cancers even earlier – possibly years –before symptoms begin, or a three dimensional tumor develops.

Here’s our conversation.

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Chuck: Nick Papadopoulos from the Ludwig Center at Johns Hopkins. Thank

you for joining us on the Good News About Cancer.

We were intrigued by some of your data that we recently saw published in Cancer Discovery in May around the issue of early detection of cancer, sometimes years before patients had a clinical presentation, as we call it, or a tumor, that might've caused the symptom. And we thought that this was really interesting about where it might take the field. So tell us about your work.

Nick: Thank you for inviting me, and I'm excited to share with you our thoughts on early detection and this particular study.

In this study we were trying to ask a simple question: how early before symptoms can we detect cancer? And why this question is important is because we develop tests, non-invasive tests, to be able to detect cancer as early as we can. It will make sense to detect the cancer not the day before diagnosis or the week before diagnosis but rather, you know, give years if possible before diagnosis.

The earlier we can detect cancers, the better the chances to provide either surgeries or therapies with intent to cure. So it was a basic question in the field. There wasn't any organized study to address well, how early can we detect them? So that's what we tried to do.

Chuck: So when you say detect cancer, many people will think, ‘Oh, a tumor that I can feel, something that's on a mammogram or an x-ray or a biopsy.’ But that's not what you did. So tell us about what you're actually detecting.

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Nick: That's a very important question. The tests that we're using, actually they are blood tests, right? That's what we used, and other people have developed that. Those tests, in essence, they don't detect cancer directly. We are able to discriminate between the DNA that comes from a cancer cell versus a DNA that comes from a normal cell.

So what we really detect is signals that, most likely come from cancer cells. That's what those tests do. So they need to be followed with imaging or some other procedure in order to really diagnose and detect the cancer that is in the body.

Alicia: You know, I think this is so exciting, especially as we try to imagine the way that we could use this in the world. I mean, if I hear this as a person who doesn't take care of cancer patients all day long, I think, ‘Okay, you're gonna be able to do this test and tell me that I have this intruder in my body, I have a cancer in my body, and I could get it out so much sooner than if I had a mammogram or if I had a PSA for screening for prostate cancer.’

What steps do we actually have to take to get there? Because this is an early study and it's so exciting, it's great news, but what actually needs to happen to get to that ideal state of where we can find these and help really get rid of cancers as they're really just beginning?

Nick: Yeah, we need, both technical innovation, and performing the appropriate, clinical, if you will, trials or studies to show that actually it has clinical utility.

So the data indicate that yes, we can detect cancer, yes, we can actually follow individuals, and in some cases we find early cancers and it seems to be making a big difference in the lives of those individuals. So it shows some feasibility. What we're missing is to have good sensitivity for cancers that actually we can do something about it.

Those are stage one, stage two cancers. And it is, of course, different than different types of cancer. You know, you can do a lot more even with stage three of colon cancer than you can do with stage one of pancreatic cancer.

So we know it can work, but we need to increase the sensitivity of the test to be able to detect those cancers that are very early, in their development.

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Alicia: You know, it's just, it's so important when we have a screening test that we want it to be highly sensitive. We want it to detect the cancer if it's there in a person, even if they're not having symptoms.

Now you did develop a test, have been working on this, and you did a really interesting study that I would love to hear you speak more about within a data set that you've been able to work with over the last few years called the ARIC Data Set. I wonder if you could tell us about the study that you did that really helped to identify and then really kind of show that you could identify cancers, even before people realized they had them.

Nick: Yes, ARIC actually is a cohort of individuals. There were a few thousand individuals that actually over, um, since I think the eighties, every few years they will give blood to create a biobank. And the goal of the study was really to take the blood and follow these individuals and study atherosclerosis. So nothing to do with cancer.

Of course, during the course of these years, from the eighties till 2013 or so, some people, besides the issues that they had with cardiovascular atherosclerosis, they were diagnosed with cancer, different types of cancer.

Now why we thought that this is a great population to answer this question that we wanted to answer you know, how early can we detect: one, they had all these bloods over the years, and two, they were not part of a cancer study, which means that there was not any management for cancer, which can change the course the disease, the cancer disease, right?

They just, one day they went to the doctor and they were diagnosed. So we thought in this environment we can really see if going back, within the history of collecting the blood, if we can really detect it.

So then we got permission to actually take blood from eight individuals from three years before diagnosis. That's where we actually were able to detect signal in bloods from individuals, three years before they were diagnosed with,cancer.

Chuck: So what kinds of cancers did you detect in those eight individuals? Was it the common cancers – prostate, breast, colorectal, and lung – or were there some unusual cancers?

Nick: They were actually common cancers. There were colon cancer, there was a pancreatic cancer, there was a breast cancer, rectal cancer. They were from common cancers that we can detect.

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Alicia: I think it's really fascinating that these cancers were identifiable in these samples by these very low levels, of course, three years before they would've been diagnosed.

And the reason is that these are not necessarily cancers that we would expect would be slow-growing. As an example, pancreatic cancer is notoriously hard for us to identify at a time point where we are able to intervene because it is relatively fast-moving and it doesn't typically have symptoms until it is really manifest in a way that is more advanced.

So this suggests that even those cancers that we consider to maybe be some of the scariest and the most aggressive, even these may have some lead-in time.

Nick: Yes. That's a great point and I agree with what you said.

So the thing that we do not know – and we cannot know in this study – is that obviously three years before diagnosis, we don't have a sample from how the lesion looked back then, right?

I think it could have been a very early lesion, very small. Who knows if it was– how visible it was in imaging or so, but they didn't have symptoms, so we do not know. Maybe it was a precancer even that, it was, detected.

I don't think that every single cancer, it will have that lightened stage. I mean, you, you kind of insinuated that there are some cancers that have an imaging and then a year later it’s stage three and four, and you know, this is bad. But not every cancer is the same, and we hope that we can catch those, that actually we can do something about it.

Chuck: So the other piece that comes up here is when we think about cancer screening, it's a very challenging area. But you have to go to a mammogram suite for your mammogram. You have to prep for a colonoscopy. You maybe go to a urologist if you want to be screened for prostate cancer.

That's a lot of visits, that's a lot of different subspecialties, that's a lot of different procedures. And this early detection through a blood test really offers the opportunity to get around all of those different individual tests, and really start with one test. That might lead to subsequent tests, of course. But it really allows one test to happen. Is that the vision that you think that we can foresee with multi-cancer early detection?

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Nick: This is the vision. I mean the acronym is MCED, for Multi-Cancer Early Detection tests. And that's the test that we and others develop.

I want to point out, although, that I'm not advocating right now, that we have to stop the standard of care screenings. You mentioned some of them. And just, um, initially perhaps this can be a test that, next to the standard of care, also it starts detecting cancers that we do not have a standard of care screening.

Alicia: So I think the good news here is that we might be able to find cancer sooner, but it's not exactly that we're finding cancers – detecting DNA is not detecting a cancer. So I think we feel like we're shifting screening. We're going to tell people they have a cancer when they don't know it, or we wouldn't catch it otherwise.

But what does that actually mean downstream? So let's imagine that there's a test and it says, ‘It looks like you've got a lung cancer, or it looks like you have a pancreatic cancer.’

What happens next to that person, Nick, and how do they actually get a diagnosis? Because it's not– it doesn't end with this test, does it?

Nick: Yeah, no, it doesn't. It needs follow-ups. This is where a different type of studies, different than the ARIC one, are very important. And we performed one a few years ago, where you give the test to some individual and then you follow them as you in the future to see if they're going to have cancer or not. If there is a signal for cancer in their blood, then usually there is some imaging that follows up to try to detect it.

And then it is possible that there will be some more invasive or minimally invasive procedures. Sometimes I call it, you know, the diagnostic odyssey that somebody has to go through.

One thing that we found was that the test result, plus imaging, actually, at least in our study, eliminated 64% of individuals that – they had a positive test, but there was an imaging that actually precluded them from having cancer, and saved them any downstream procedure, like a more invasive procedure.

And I think those tests are going to work in combination. So having this test plus, you know, the least invasive, if you will, procedure, which will be imaging, especially if it's imaging without radiation. I think that, how I see it in the end, you know, this test working.

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Chuck: I am going to go one step further. I have a blue-sky projection here where – maybe not for all cancers of course, but for some – we might be able to detect a cancer in the blood. We may not even detect a tumor with imaging. And then we might skip right to a therapy. And when you look at what's happening with tumor vaccines, and other approaches, you may see a path down the road where a person has a test, it's positive. It says, okay, this indicates, I'll say melanoma for example, and we have melanoma vaccines that we can deliver that are already showing clinical benefit.

Now, we're not there yet, but your work and the work of others is making progress along one of those two arms, which is that early detection. So what we now need to do are the trials that look at the intervention. But I don't think imaging is the next step in all cases. It may be other factors.

Nick: Actually this is, I have to say this is music in my ears and it was something I'm glad that came up. We do believe in that. Again, it has to do with how good those tests work.

Currently, I think without imaging, I don't think anything is going to, you know, it has to prove. But as you said, this is more futuristic.

I don't think it's farfetched, by the way. I think that this is something that us and others have been thinking for a long time, and I think for certain situations it may be closer than we think.

Chuck: Right. Very treatable cancers, detecting them early. We might detect them before a tumor develops. We might be able to spare the organ, whether it's the colon or the breast or the prostate or whatever. We might be able to spare the patient a lot of potential morbid, or high side-effect, types of therapies.

Alicia: Nick, as you consider where we go next steps, what are really concrete next steps in the next two years, five years or so, even 10 years, that you think: we can achieve these, and this is where we're going, I really want people to take home this message, as they think about these multi-cancer early detection tests.

Nick: We need the studies. Prospective interventional studies, to understand not only what we can detect, but how this affects the individuals. That’s what I think needs to happen. I know it doesn't sound like a huge innovation, we can innovate, but that is some concrete steps that we have to do. Plus education, potentially even to the physicians, not only the public.

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The other thing that we need to keep in mind is: early detection and development in therapeutics, it goes hand in hand, right? I mean, we need to be able to have weapons to treat these cancers, even pre-cancers, right? So drugs that we use now in stage four cancers, they have a great chance to work better when you have a smaller cancer, which usually it's early stage and that I has a higher chance for a good outcome.

Chuck: So those clinical trials are going to need to be done. They're going to take a fair amount of time. But, I think worth doing, because they offer so much to the prospective patient, to spare them potentially toxic therapy.

Well, Nick Papadopoulos from Johns Hopkins, thank you so much for your time today and for all of your work in this area, both past work in this area, sharing it with us today, and then the future work that we're going to be watching with keen interest.

Nick: My pleasure and, thank you for having me at your podcast. ____________

Chuck: That was Dr. Nick Papadopoulos, a professor of oncology, pathology and human genetics at the Johns Hopkins University School of Medicine, talking with me and my co-host, Dr. Alicia Morgans.

You know, I think the big takeaway from this conversation is a couple of things. One is that tumors can be detected in the blood years and years, perhaps, before a clinical cancer develops. And by clinical cancer, I mean a symptom or something even that shows up on a scan. And that's big news.

The other key takeaway is that this is not testing for one cancer at a time. The whole point about the next generation of early detection is we're going to break away from that linearity: today I test for prostate cancer, tomorrow I test for colon cancer. No, today it's: we're gonna test for 50 cancers, and that's a big deal.

And as a matter of fact, we're going to talk about that in an upcoming episode with Dr. Tom Beer from Exact Sciences, where they have developed and already rolled out a multi-cancer early detection test that is commercially available. So stay tuned for that. And thanks for listening to the Good News About Cancer.

I'm Dr. Chuck Ryan at Memorial Sloan Kettering Cancer Center in New York.
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The views we express on this show are our own and do not represent the views or opinions of the institutions where we work.

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