Do multi-cancer detection tests provide a net benefit? NCI aims to answer this question, beginning with the Vanguard feasibility trial which recently started accruing patients.
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Sara Willa Ernst, The Cancer Letter’s newest reporter, made her The Cancer Letter podcast debut this week to talk about her first cover story: The launch of NCI’s Vanguard feasibility study.
Sara was joined by Paul Goldberg, editor and publisher of The Cancer Letter, and Claire Marie Porter, reporter, to talk about the Vanguard trial, which is the newest development in the story of multi-cancer detection tests.
“Is early detection always good? Especially when we’re talking about the very very early stages?” Sara said.
This is one of the questions at the heart of NCI’s approach to studying MCDs, and one that is becoming increasingly urgent at a time when science is imperiled by funding cuts.
“When are you doing good, and when are you doing harm?” Paul said. “Which is actually incredibly timely, because the word is that the U.S. Preventative Services Task Force, all of the members are likely going to be fired by Kennedy, and AHRQ is going to be cut. So the greatest achievement of evidence-based medicine in the world is about to be dismantled.”
Stories mentioned in this podcast include:
- Will MCD tests revolutionize cancer screening? NCI begins enrollment in Vanguard “feasibility” trial to start finding out
- Robert Winn: If Medicaid gets massive cuts or goes away, where will these patients get care?
- Oncologist biotech entrepreneur George Tidmarsh joins FDA as CDER director His appointment came out of “proximity” to Makary and Bhattacharya
- FY25 paylines drop to 4th percentile—a historic low—as NCI braces for Trump’s FY26 budget cuts
- Right-wing provocateur Laura Loomer comes for FDA’s Vinay Prasad
- The effects of NIH, FDA cuts will be felt for decades, CBO report estimates
- NIH says it’s moving away from animal-based models
This episode was transcribed using AI transcription services. It has been reviewed by our editorial staff, but the transcript may be imperfect.
The following is a transcript of this week’s In the Headlines, a weekly series on The Cancer Letter podcast:
Jacquelyn Cobb: This week on The Cancer Letter Podcast…
Sara Willa Ernst: Is early detection always good, especially when we’re talking about the very, very early stages, in which we don’t really know what’s going to happen? As somebody who has a health reporting background, but not a lot of cancer reporting background, that was actually really surprising to me. I think probably most people from the outside world just assume preventative early is better, but it’s a lot more dicey and just nuanced than that simple narrative.
Paul Goldberg: When are you doing good and when you are doing harm? I mean harm from prevention, which is actually incredibly timely because the word is that U.S. Preventive Services Task Force, all of the members are going to be likely to be fired by Kennedy.
You are listening to The Cancer Letter Podcast. The Cancer Letter is a weekly independent magazine covering oncology since 1973. I’m your host Paul Goldberg, editor and publisher of The Cancer Letter.
Jacquelyn Cobb: I’m your host Jacquelyn Cobb, associate editor of The Cancer Letter. We’ll be bringing you the latest stories, groundbreaking research and critical conversations shaping oncology.
Paul Goldberg: Let’s get going.
Claire Marie Porter: Hi everyone.
Paul Goldberg: Hi Claire.
Claire Marie Porter: Good morning. Hi, Sara. Welcome, Sara. This is Sara’s podcast debut. How’s it going? Do you want to just tell everyone who you are and how long you’ve been with TCL?
Sara Willa Ernst: Yeah, I’m a new reporter at TCL and this is the beginning of week four and I’ve already written my first cover story which is what we’re talking about today.
Claire Marie Porter: So exciting. Anyone do anything interesting this weekend? Paul, you’re still in Vermont, I presume?
Paul Goldberg: Oh, no. I didn’t want to leave, but I will eventually have to. I’m just kind of gearing up to start to go into a writing frenzy on my novel. Since they’ve been flooding the zone in Washington, I really haven’t had a chance to do much of anything other than try to navigate the floodwaters, but now I’m able to sit down and actually focus, sort of, starting to.
Claire Marie Porter: Speaking of navigating floodwaters, it reminds me. Brought this image to mind of, I went tubing with some of my family members this past weekend, but none of us had really proper tubes. Some of us were on a mattress and some of us were on inner tubes that come from a tire and then some just regular blow up tubes. I was on the mattress and it got caught on a rock. It was so scrappy, a little trashy. The water was very brown. I don’t know what was going on, but we were floating down on this mattress, I think four or five of us, with three children and got caught on a rock and it just popped. We all just kind of sank and had to walk back. I don’t know what your flotation device of choice would be, but mine would not be a mattress after this weekend.
Paul Goldberg: Well, I’m glad everybody is okay and that there’s no poisoning from the brown water.
Claire Marie Porter: Yeah, it was like two feet.
Paul Goldberg: Okay.
Claire Marie Porter: Well, Jacquelyn is out today. She’s on her way back from Peru, so we’ll finally have her back next week, I believe. I mean, she’s coming back today, but we’ll record with her next week. I’ll give the rundown and then we can talk about the story behind the story. Last week, story two, Sara, spoke with Robert, a win about the impact of Trump’s Big Beautiful Bill on Medicaid patients. I wrote a story about George Tidmarsh being named FDA Center for Drug Evaluation and Research or CDER director at at FDA. Tidmarsh is an oncologist and a long time pharma executive. Cancer policy, as always, had some important stories. Last week we had NCI is dropping pay lines to the fourth percentile and Laura Loomer’s latest Target, Vinay Prasad. We had a CBO report on federal health cuts and NIH’s new policy on animal testing.
Finally last week, Sara took charge of her first lead story, as she mentioned. My understanding from the outside was reporting this story was a bit of a comedy of errors of sorts, so it sounds like Sara did an awesome job of rolling with the punches. The cover story, it was about the official start of NCI’s Vanguard feasibility trial of multi-cancer detection tests. This was the most recent installment of Jacquelyn’s coverage of MCDs. This was going to be Jacquelyn’s baby. Then the story behind the story started about two weeks ago when Jacquelyn was hit with a sickness while in Peru. Jacquelyn told me that Paul probably has a joke about being a colonizer in there, but I’m going to roll through, so you can’t make that joke. Paul took on the scheduled interview for Jacquelyn while she was out sick, but then Murphy’s Law, Jacquelyn was out again for another planned trip, so Paul ended up recruiting Sara to help make the Vanguard happen in Jacquelyn’s absence.
Sara, a little bit of trial by fire. What was the experience like? This is a story that has all of this historical context and drama and years of backstory and is really complicated just at face value. What was that like?
Sara Willa Ernst: I found it really fascinating, just kind of diving headfirst into the world of early detection and really what is the forefront of early detection. The headline and really kind of the core of the story is that, are MCDs going to completely revolutionize early detection? Those are some of the main questions that are being wrestled by the Vanguard study, but of course, it’s starting with a feasibility study before it really gets into the meat and potatoes of investigating the endpoint of mortality. Yeah, me and Paul, we talked to Philip Castle at NCI. He also spoke to Scott Ramsey at Fred Hutch and those are two of the main people that are in charge of the Vanguard study. I think they’re quite hopeful, cautiously optimistic about the outcomes of both the feasibility and then also the bigger trial that could come after it.
Paul Goldberg: You don’t want to be too optimistic because then you lose equipoise and then you have to kill the trial. The objective, well, there’s really nothing more complicated than cancer prevention stories. It was great to have Sara dive into it. It was almost like a battlefield commission because Jacquelyn, who was going to be in charge of the story ended up getting sick in Peru. I’m not going to make the joke that Claire didn’t want me to make, but I will make another one. Yeah, yeah, yeah. Imperialism jokes are always good. Crowd pleasers, but I will quote or paraphrase Winston Churchill in saying that, it’s better not to know how laws and sausages are made and how news stories are written would be my paraphrase, so this one was really interesting.
It was actually the interview, with Scott Ramsey, was going to be happening with Jacquelyn, but Jacquelyn was unable to do the interview, so there I was, which was wonderful to have an excuse to talk with Scott and it also turned out to be kind of hilarious on the personal level because we started kind of veered off talking about bicycles and they realized how badly I wanted a gravel grinder bike. This has nothing to do with cancer prevention and early detection, I hope. I ended up starting to kind look and when you look, you find, so I got a specialized diverge bike, which is coming shortly to me in Stowe and I’m looking forward to doing some riding. Anyway, I can talk for hours about bikes and poor Sara had to listen to this idiocy, as did the staff members at the Fred Hutch, as Scott and I were talking about bikes.
Time for a quick break. Let’s hear from our sponsors. Coming to you from Nashville, it’s Stand Up To Cancer. Join us for one night with one goal, beat cancer. Tune in Friday, August 15 at eight or seven central on ABC, CBS, Fox and NBC. For more ways to watch, visit standuptocancer.org/show.
Claire Marie Porter: I do have some questions about the actual story, but I did have another question for you, Sara. I was just wondering, I feel like every journalist has had some experience of being thrown into a story where they feel a little bit over their head and have to just fake it until they make it, but I was wondering what your process was for when you found out you’re going to be a part of this story. Where did you go? What did you do? Did you do some background research or just talk to Paul a lot or?
Sara Willa Ernst: Yeah, definitely background research, but I actually received a torrential downpour of audio messages from Jacquelyn. Not quite in the full throes of her sickness, but towards the tail end in which she was able to articulate words, but she gave me a very thorough rundown of the who, what, where, when, and why and also the stakes and what she thinks are the most interesting questions. Even though Jacquelyn, she wasn’t there for the interviews, I think I was a conduit in some ways for her robust background knowledge about the topic. Yeah, read a lot of articles and chatted with the people at NCI, read the press releases. Just kind of on my own, thought through some of the biggest questions of early detection. Is early detection always good, especially when we’re talking about the very, very early stages in which we don’t really know what’s going to happen? As somebody who has a health reporting background, but not a lot of cancer reporting background, that was actually really surprising to me. I think probably most people from the outside world just assume preventative early is better, but it’s a lot more dicey and just nuanced than that simple narrative.
Paul Goldberg: When you’re doing good and when you are doing harm, I mean harm from prevention, which is actually incredibly timely because the word is that the U.S Preventive Services task force, all of the members are going to be likely to be fired by Kennedy and also AHRQ is getting cut. The greatest achievement of evidence-based medicine in the United states and possibly the world is about to be dismantled. I cannot imagine how anyone is going to be able to guide the consumer through issues such as MCDs without the US Preventive Services task force. It’s a huge story. Huge and you walked into it. To your point, Claire, you can’t fake knowledge on this one. You either really understand the fundamentals and know what you don’t know or you ask somebody who does and in this case, we were all working together very nicely.
Claire Marie Porter: Well, we’ve been covering this story for a few years now. Why is this story important? What’s new here?
Sara Willa Ernst: I mean, the trial is starting right now. This thing that has been kind of in the works for a while is starting and it will take three to four years to really get a sense of the feasibility part of the trial and whether or not they’re going to move forward with a more robust trial or whether it’s going to get rolled in, but I think it’s a good time to just check in with the researchers on really what are those final decisions that they made when it comes to the design of the study.
Paul Goldberg: I mean, the main question is, can you even do the study and where because here’s a study that randomizes participants into three groups. One is one modality or another modality or a control group. Now what happens when people on the control group decide to take another test because they’re nervous? Then you lose them and does it compromise the whole trial? What are the risks? What do you tell people? How do you set it up? Will doctors know what the heck they’re doing because it’s not a very straightforward design? Oh, what happens when the technology is altered because this technology is rapidly changing.
Sara Willa Ernst: That was a really interesting part of our interviews with Philip Castle and Scott Ramsey. When you asked questions about, this is going to take a couple of years, but will the technology change by the time that we get the results of the trials? I remember Scott Ramsey saying, okay, you’ve gotten to one of the core anxieties that I have throughout this whole thing.
Paul Goldberg: Yeah, that was before we started talking about bicycles. Yeah, no. It’s really an astonishing set of questions of where technology and may be just sort of ahead of our ability to regulate it, to deal with it, to guide consumers and to guard from harm. I mean, harm is real. When you get a false positive or a false negative result, it’s harm.
Claire Marie Porter: That was my next question, was what are some of the cons of MCDs? I assume false positives, over screening, over treatment, that whole deal?
Paul Goldberg: Well, Sara, do you want to take that?
Sara Willa Ernst: Yeah, yeah, exactly what you said. The possibility of the technology not even really working as well as the promises are saying it will. False positives, false negatives, but then when people do get, let’s say, a more accurate test, the impact of over-treatment. Then there’s also the question of is this really necessary? The vast majority of MCD tests are going to come back finding nothing and so there’s also the question of the impact on the finances and how it’s going to be afforded and whether or not this will be covered by insurance companies, whether or not this is kind of medically necessary, when the vast majority of people will get negative tests because they don’t have cancer.
Paul Goldberg: What does a negative really mean and is it a false negative? It’s interesting because it was just as an illustration of how confusing this can be. I was at a journalist’s, science writers meeting last year and one of the writers, science writers said that she got a concerning mammogram and so she took one of these tests and it came out negative, so she was calmed by this and that is precisely how you don’t use this. That is precisely how not to. Given America’s healthcare system’s track record of making the worst of every invention, not every invention, many inventions, this can go take us straight into the wilderness. Also, how do you follow up on this? This is all very interesting territory and I’m glad that you got into it so quickly.
Sara Willa Ernst: I’ll add something too to what you just said. I mean, I think the ultimate promise with people having their head in the clouds and being like, what could this ultimately mean for early detection? It’s like, yeah okay, you just give one drop of blood and then suddenly the answer to whether or not you have 20 to 50 different cancers, but talking to folks at VCU, folks on the ground that are going to be administering the trial and talking to patients, especially primary care physicians that I spoke to. The feeling is very much, at least in this early stages, the process is going to be MCD test and then kind of the more traditional early detection tools or just detection tools. It would be like MCD test and then let’s verify with a mammogram and then do a biopsy. The traditional cancer detection tools aren’t going to totally become obsolete overnight. They’re going to be used in tandem.
Paul Goldberg: Well, there’s an argument to be made here and it was made actually in The Cancer Letter by Peter Bach, who is of course part of Delphi, which makes such a test, but his suggestion was that these tests should be used only in settings or to be used in settings where another test exists, so like colon cancer, lung cancer and so forth. That sort of makes sense. A test that can actually verify, it would be nice to use it in something like pancreatic, but there is no other test in pancreatic, but that’s where the need is particularly urgent. It’s a lot of scientific questions, more than you can even imagine at this point because the trial hasn’t done, which is why it’s great to do the trial. To me, the most important piece of this was that NCI is still in business. It was nice to talk to Dr. Castle about the fact that here is a major clinical trial initiative that’s asking a question that a lot of people find very, very important right now.
Claire Marie Porter: Yeah. How does NCI feel about MCDs as this Vanguard gets going?
Paul Goldberg: Well, I mean, it doesn’t matter how they feel. What doesn’t matter is, yeah, it is. What they feel and what they think is that the main question is mortality endpoint, which by the way is often confused with survival endpoint, but that’s a lecture that you both have heard enough times and our listeners don’t need to because they understand it too. Yeah, so the main question is, does it affect mortality? Not just late stage diagnosis, but mortality. That’s the big question that solves the whole thing, but it takes years to answer and once you take those years to answer, the technology doesn’t stand in place and it moves forward and oi.
Claire Marie Porter: I see. Well, super interesting you guys. Thanks for chatting. I learned a lot. Well, thanks for listening and we’ll see you next week.
Jacquelyn Cobb: Thank you for joining us on The Cancer Letter Podcast, where we explore the stories shaping the future of oncology. For more in-depth reporting and analysis, visit us at cancerletter.com. With over 200 site license subscriptions, you may already have access through your workplace. If you found this episode valuable, don’t forget to subscribe, rate and share. Together we’ll keep the conversation going.
Paul Goldberg: Until next time, stay informed, stay engaged and thank you for listening.
