Cancer Early Detection: Beyond Mammograms and Colonoscopy

Dr. Alicia Morgans: This is The Good News About Cancer. I'm Dr. Alicia Morgans.

Dr. Charles Ryan: And I'm Dr. Chuck Ryan.

Alicia: We're oncologists, and we've spent our careers working to understand cancer. We believe that there's more progress now in research and treatment than there ever has been, and we're here to share that with you.

Chuck: In each episode of the show, we're going to talk to one of our colleagues about a new development in cancer treatment or diagnosis. We'll break down what's new, why it matters and how it points a new way forward.

Dr. Margaret Tempero: Now we have a number of cancers for which screening has clearly proven to be useful in preventing the incidence or decreasing the mortality, so the fact that I've been able to see that in my career just gives me a tremendous hope.

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Alicia: All right, Chuck, what do you think is the easiest cancer to treat? 

Chuck: Well, I would say that there's two answers to that question. The first is the cancer that never develops, like when you prevent one through a vaccine or through something like that. But after that, the easiest way to treat a cancer would be to detect it before it even forms a tumor or causes a symptom or causes a problem for a patient when you can eliminate it minimally.

Alicia: You know, when I think about people out in the world, nobody wants to worry about cancer. And if they can do a test to find it before it's really even a tumor, if it's just some DNA floating around, or if they can know that they're going to get something and then take a medicine or do something to prevent it, it would just be so transformative and really just sort of lower the temperature on cancer for everybody.

Chuck: Do you know that it takes over 2 billion cancer cells to make a measurable tumor that you would see on a cat scan? About a two centimeter tumor. At least that's what we know about in prostate cancer. And think about it: that means that somebody could have 1 billion cancer cells in their body and not have a tumor, but if we could detect half a billion or a hundred million or a million cancer cells and get rid of them before they multiply even further, that's the promise of early detection.

Alicia: You know, when I think about early detection, I really just want to make sure we all are on the same page around that. There are different ways we can have early detection. We can detect something when we measure something like a PSA in blood, and then we know that somebody might have a prostate cancer. We use early detection when we do a mammogram and we find a small breast cancer that we can remove and maybe do some radiation after that surgery to try to cure the person.

But early detection at present, at least, is really finding a tumor in most cases, so that we can do early surgery or do early radiation or do some early medicine to try to stop it from spreading and causing long term problems. 

But early detection, I think, is moving even earlier and it's expanding from those few cancers that I talked about to cancers that are more broad so that more and more people can be affected and hopefully not have to worry about cancer over their lifetime because things can be treated or detected before they ever become problems and it's so important and exciting that this might be possible.

Chuck: This is something that you and I aren't going to solve but Dr Margaret Tempero from the University of California, San Francisco has started an initiative there on early detection of cancer. She is a pancreatic cancer specialist for many years and has had a great career.

She has been the president of the American Society of Clinical Oncology. She edited the journal of the National Comprehensive Cancer Network. And when I was recruited to UCSF some 20 plus years ago, she was the chief of oncology there. So I've known her for a long time and owe her a debt of gratitude for my career. 

So here's my conversation with Dr. Margaret Tempero from UCSF on the topic of cancer early detection.

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Chuck: Margaret, it's great to see you after so many years of working together and seeing new initiatives pop up in your life and in cancer in general. You are now leading the Cancer Early Detection and Interception Initiative at UCSF and this caught our eye as something that's really interesting that we thought the public should know about. So tell us a little bit about what it is and how it came to be.

Dr. Margaret Tempero: This all came about because I had spent 40 years taking care of pancreas cancer patients. And most of the time I was saying goodbye to them. And I couldn't do it anymore. 

And I thought I needed a break, and I needed to do something different. And so I thought about early detection. Maybe I would take a sabbatical and focus on early detection of pancreas cancer. So as I thought about it, and I realized all the tools and technology that are now available to us, I thought my vision was too narrow.

So I went to our cancer center director, Dr. Alan Ashworth, and I said, you know, I think I have a vision for something bigger, and that's a unit that's focused on early detection of cancers for which we have no strategy right now. And providing services related to that and doing research related to that. And I was really just asking for advice. But after the end of a very animated hour, I had a new job. And that was this new initiative. 

So I have been on sabbatical, working on it, and realizing the complexity of it. But I'm no less enthusiastic than I was last year at this time. I'm very excited about what the future holds. With new technology, new strategies, it's a whole different world than the world I trained in, for example, or even the world that you trained in.

Chuck: Right, right. Early detection of cancer – what did that mean earlier in your career, versus what does it mean now?

Margaret: When I started my career, we had no strategies for early detection. If we detected a cancer early, it was pretty much an accident, with the exception maybe of breast cancer because we were already doing at least self-exam and some imaging – but the imaging has improved so greatly over time.

And now we have a number of cancers for which screening has clearly proven to be useful in preventing the incidence or decreasing the mortality. So the fact that I've been able to see that in my career just gives me a tremendous hope that we can carry on and do it faster. 

Chuck: Where is it now that early detection is done, and pays off?

Margaret: I think the most glorious example, actually, is in colorectal cancer. Where we've seen sharp decreases in mortality every time the statistics come out. And it's largely due to screening and early intervention. 

This is a disease that develops from a benign process to a cancerous one. And so with the use of colonoscopy, identifying the benign tumors, removing them – or early cancers – and having those addressed surgically, we've made a huge impact.

That said, you know, only 60% of eligible people are undergoing screening. And there are a lot of reasons for that. They might just not want to have a colonoscopy, or maybe they're a service worker and taking off time for a colonoscopy prep and the procedure means you don't get paid for two days.

So now there's advances with looking for tumor-associated DNA in the stool and now in the blood. So when you think about it, this is going to really increase the number of – I hope – increase the number of people that are willing to do some form of screening. Because it's absolutely true that even an inferior form of screening is better than none at all.

And so this could make a huge difference, a recent approval of a blood test now to detect colon cancer.

Chuck: So tell us a little bit about the blood test. 

Margaret: So the blood test is picking up circulating tumor DNA, minute amounts. It's very good at detecting stage 2 disease, which would be not confined to the colon, but into the muscle layer. It's not so sensitive it can pick up stage 1, but it probably doesn't matter. Because most stage 2's are curable, even most stage 3's are curable, and that's where it's grown all the way through the muscle wall of the colon. 

So it doesn't mean that we should walk away from the gold standard of colonoscopy, but for folks who, for whatever reason, can't get that done, this is a great option. And you can think of, too, of the advantages in a resource-constrained country where perhaps they can't even do colonoscopy because they don't have the capacity to do it.

Chuck: So, that's the paradigm. That's the model. We want other cancers to be like colon cancer in that regard. Saving lives, early detection, leading to an early recovery, interception. And cancer early detection done up until now has depended on the presence of a three dimensional tumor that you can see, that you can measure on a CAT scan or an x-ray or a mammogram or something like that. And I think one of the hopes of early detection might be that we can detect cancer before there's a tumor. Explain for listeners what I mean here, the difference between cancer and a tumor.

Margaret: So I'll use pancreas cancer as an example here because it's a really good one. Pancreas cancer is– when you look at the tumor on an x-ray, a CT scan, for example, the majority of that lump that we call a tumor is not actually cancerous. It's kind of an inflammatory reaction around the cancer cells. So it makes the tumor look really big, but actually the number of cancer cells in that lump are quite scant. 

In fact, here's the challenge, because the tumor detection assays in the blood that depend on circulating tumor DNA means the tumors have to die, and that DNA has to be shed. And if you don't have very many cancer cells in that lump we call a tumor, it's unlikely that that will be picked up on a blood test. 

So we have to think about other things that we can measure that might say that that lump or absence of a lump, you don't even– haven't even looked for a lump yet, right? That there might be a signal. 

So things like immune cells that sense that something is not right, they will give off proteins that can be measured in the blood. And some of these have profiles that are characteristic of different types of cancers. So, we think that the blood-based assays are going to need to be optimized to look at other types of material things that could signal an underlying cancer.

So not just the tumor-associated DNA, but the body's reaction, if you will, to the tumor as it's evolving and growing.

Chuck: So that’s a whole new body of technology. And you started by saying cell-free DNA or circulating tumor DNA. And that requires that there be a tumor. You have to have a certain number of cells. So the circulating tumor DNA will probably never be early enough, is I think what you’re saying. 

Margaret: In some diseases I think going to be true. That's going to be true. So then we have to be thinking about, okay, how do we take advantage of circulating tumor DNA to find some cancers, but take advantage of others processes, physiological processes that happen as a cancer is evolving, and add those into the– into the test, if you will.

So you're, you're looking at multiple different, we call them analytes, different types of, of things that you would be measuring in the blood that could reflect an underlying diagnosis of cancer.

Chuck: Tell us a little bit about whether or not you envision a day when we have a pan-cancer – which means any kind of cancer – test, that would be administered by a family doctor. Is that something that we are– is that your goal? Or is the goal for this to be used by specialists who are concerned about at-risk individuals and doing the test only in at-risk individuals?

Margaret: I think the job of cancer screening has always been in the primary care area. And I think it will always remain in the primary care area. But where I see a shift is that as a primary care doctor, you are dealing with lots of things. Cancer is only one of them, right? You are watching out for hypertension, high blood pressure, you're watching out for cardiac disease, you're watching out for diabetes, you're watching out for obesity, you're watching out– trying to make sure that your patients are healthy across the board. And cancer is only one of those things. 

So for the primary care doctor to be able to do the testing – in the ideal world, a blood test that would detect clinically significant cancers, so clinically significant ones, and then to be able to hand that patient off to a diagnostic center so that they can get an efficient workup. The primary care doc isn't necessarily connected to the specialist in advanced endoscopy, for example, who might be the person who would help you work up a pancreatic cancer. 

So that's why we are developing a cancer diagnostic service at UCSF. So that patients, if they have a positive signal, can come to us. We can do the workup very efficiently, and then we can hand that patient off to the appropriate team.

Chuck: So, tell us about the cancer early detection and interception initiative at UCSF. Can people come to this as a patient? How are you progressing in terms of developing this as a model clinical enterprise?

Margaret: Well, right now we're working with the primary care docs whose patients are coming to them and asking them for either whole body imaging, or a blood test because of their concern about having cancer. Not that they're symptomatic, but they want to remain healthy and they know that early detection is important.

My dream– my dream is that, eventually, we will make this into a cancer risk and diagnostic services, because I really feel that there are so many modifiable risks that people may not be fully aware of.

One of the ones that is sort of low hanging fruit is really whether you have an inherited predisposition for cancer. That might be very evident from looking at your family history, for example. And eventually, I think, because some families are small and not everybody has a positive family history who has an inherited predisposition, I think eventually we'll be doing genetic testing on everyone.

And basically identifying early on who has a predisposition for breast and ovarian cancer, for example, or for colon cancer. And that'll change our strategy and personalize our strategy for screening in a very transformative way.

Chuck: Imagine what life would be like as a medical oncologist in that era. Where we're not treating advanced cancers that we can't cure, we're intercepting them, and intercepting the risk and maybe even modifying lifestyle or other factors, in that at risk, but no cancer stage, to prevent the patients from getting cancer.

It's almost like we oncologists could become like firemen are. You know, they do inspections in buildings and make sure that they reduce the fire risk. They put up and make sure that there are all kinds of preventive services. But if the fire happens, they're there to fight it too.

Margaret: I think I'm going to use that analogy. I like it.

Chuck: I just made it up actually. So yeah, we'll, we'll, we'll trademark it and then, uh, yeah, it's all good. 

So, if somebody can't come to San Francisco, and they're interested in what you're doing, and/or if they want to do one of these tests, do you recommend currently in 2025 that an individual ask for a test, if they're feeling well and just want to be as healthy as possible?

Margaret: No, we don't. We think that we need more good validating evidence that these are clinically useful tests and we're waiting on the results of trials that are already in progress. So I think we need more solid data before we can routinely recommend these tests. So we're not promoting them, but we do feel that the value needs to be understood and the clinical trials need to happen. 

So I think we're at the beginning of something. We're not anywhere near the end, and we're not quite at the very beginning, but I think we're– we're starting to understand how and where to look.

Chuck: To paraphrase Churchill, we're not at the end. We're not even at the beginning of the end. But maybe we're at the end of the beginning. Is that what you just said? 

Margaret: Well-said. 

Chuck:  Okay, well, Dr. Margaret Tempero, it's been a real pleasure chatting with you today. This is a fascinating area where not only is the science fascinating, and we really just scratched the surface, but the opportunity to prevent death from cancer and intercept this disease, that affects millions of Americans, is really exciting. And I, I congratulate you on this effort and, and telling us some of the good news about cancer coming from your world. 

Margaret: Thank you. It's an exciting journey. 

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Alicia: Chuck, that was really such a great conversation. So engaging, really enlightening. 

Chuck: We're still at the beginning of the story around early detection. We have tried and true methods that have been around for a long time, mammograms, pap smears, PSA tests, et cetera. But the other cancers where early detection is not possible are the ones where people run into real problems. And I think we're really hopeful that we're going to see more early detection around conditions like bowel cancers and pancreatic cancer and things like that.

Alicia: Well, I'm excited to see where it goes and really, really happy that we are getting started on the right foot. 

So, my name's Alicia Morgans. I'm a medical oncologist at Dana Farber Cancer Institute in Boston.

Chuck: And I'm Chuck Ryan, a medical oncologist at Memorial Sloan Kettering Cancer Center in New York.

Thanks to Lilly for support of this show. 

Our production partner for this series is CitizenRacecar. This episode was produced by Anna Van Dine, with post-production by Jose Miguel Baez.

Alicia: And there's a whole lot more good news to talk about, so make sure you subscribe to this show wherever you listen to podcasts. And if you liked this show, or you didn't, please share it with someone you think might find it interesting. 

Chuck: Cause even if you didn't like it, the people you pass it out to probably will. 

Alicia: We'll be back again soon with more good news about cancer.