Screening for cancer is like Mom and Apple Pie. Who would be against it? Intuitively, early detection should allow for early treatment and higher survival rates.

Vinay Prasad is an oncologist and professor of epidemiology at UCSF. His provocative thesis is that cancer screening is over-rated – or at least is based on flimsy evidence. He argues that identifying a cancer on biopsy does not equate with a full understanding of its long-term behavior. He makes several important points in his podcast on EconTalk with Russ Roberts.

“And, some of these lesions that we find are definitely the sort of lesions that are going to kill you. Some of the lesions are the sort of lesions that are going to kill you were it not for cutting it out in that moment. So, if you catch it early and cut it out, now it’s not going to kill you.

Some of them, they’re going to kill you regardless of whether or not you cut it out. It’s already spread, the damage is already done.

And then some of them are lesions that might not cause you harm in the rest of your natural life. And, that’s a very counterintuitive idea and something people called over-diagnosis.

And, the problem with screening is that it has to have the right balance of these things. You have to catch a lot of the cancers that, if you didn’t find it would’ve done something bad, but now that you found it, we have a good outcome; and not so much of the ones that they’re going to do something bad anyway. That’s just adding extra time, anxiety, to your life and not so much of the ones that aren’t going to do anything.”

So, it’s complicated.

“The metaphor is a barnyard metaphor. And, the metaphor is basically, like, imagine you’re a farmer and you have a barnyard and you have lots of different animals in your barnyard, and you want to find a way to keep the animals in your barnyard. And, that’s, I think–the idea of catching the animal before it leaves the barnyard is the metaphor for catching the cancer before it causes a problem.

And, one can imagine there’s three types of animals in your barnyard. There are rabbits, turtles, and birds. The thing is the fence, it’s going to be really good at catching those rabbits. They are hopping, they’re jumping, and when they get to the fence, they’re going to be stopped and they’re going to come right back to your yard.

The turtles–actually turns out you probably didn’t even need the fence. They’re moving so slowly that even in the next year or two, they’re not going to get outside your yard. This is how the metaphor goes.

And, the birds, meanwhile, are moving so quickly that no fence can stop them. They’ve already flown right out of your yard. And, those are also cancers.

So, the idea is that the turtles, the birds, and the rabbits are all cancers. Some cancers are so aggressive that even when you screen people, they have already spread.

And, in fact, Russ, I would just say that when you look at all of the screening tests we’re going to talk about today, and maybe the ones we’re not going to talk about, one thing to point out to the listeners is that no screening test reduces death from that cancer to 0%. So, we debate how well they work. We debate the benefits and harms.

But nobody debates the fact that you can get all the colonoscopies you want and there’s still a risk of dying of colon cancer. You can get all the breast cancer screening you want. There’s still a risk of dying of breast cancer. Typically, that risk is 80% of the risk. I mean, even the proponents think it only lowers cancer death by 20%. What that means is there’s a lot of birds. There’s a lot of birds.

And then the other thing, Russ, is we should have some humility in medicine. We don’t know how many turtles there are. And turtles matter a lot. Because, every time you find a turtle, you’re going to treat that person as if they had a rabbit or as if they had a bird. They’re going to get the full-court press of treatment. But they may not have needed much of that treatment or even any of that treatment. And so, that’s just harm being inflicted on someone. So, this is the delicate balance of screening.”

Most patients with prostate cancer die WITH prostate cancer; not of prostate cancer.

Some of our treatments have become so good, that screening may not even make sense. He uses testicular cancer as an example. Should men examine their testicles every month in the shower? Dr. Prasad argues no.

“As one example, in testicle cancer since the 1970s and 1980s, we can cure testicle cancer even when it’s spread everywhere. Like Lance Armstrong. Our cure rates are like 95%, 96%, 97% for metastatic testicle cancer. So, actually, because we can cure it so well when it’s advanced, there’s no longer an impetus to find it early.

And the USPSTF–United States Preventive Services Task Force–says: Don’t examine your testicles every month in the shower. It’s USPSTF Grade D because you’re only going to find incidental things that lead to losing a testicle, which is the way we actually–we don’t biopsy a testicle; we actually just remove it. And, even if it presented late, you still have an excellent result. So, there’s no differential to exploit.

And finally, the thing I’d say is our treatments are getting better for breast cancer, prostate cancer, etc., and the advanced disease, which many of us believe is eroding whatever benefit of screening was there in the first place.”

What harm is there with screening? Of course, all screening tests have risks. If we use colonoscopy as an example, there’s a risk of bowel perforation, including death. But the risk is low. The main risk is the inconvenience of the bowel prep. Dr. Prasad continues:

“What I would say about colon cancer screening is that until this year, this last year, there were zero randomized studies of colonoscopy; and many European nations did not recommend colonoscopy as that was the intervention that went beyond available data. The United States has been doing colonoscopy for a long time–based largely on some of the other considerations we’ll talk about, and our financial biases–but other nations weren’t.

So, what was the data? The original colon cancer screening was something called Fecal Occult Blood Test or FOBT. It’s basically smearing feces on a card and looking for occult blood–little bits of blood in it that you didn’t feel or see. And that was the original test. And, that has multiple randomized trials that show reduction in dying from colon cancer. So, you’re less likely to die of colon cancer, but you’re no less likely to die for any reason.

The Minnesota FOBT study has absolutely super-imposable survival curves for all-cause mortality. You look like you did the same.

We switched maybe about a decade and a half ago to the fecal immunohistochemical test or FIT. That’s a different kind of card technique that you poop on a card. It looks for different things, but it has slightly better test characteristics–a little more sensitive and a little more specific. And so, people can say it’s a reasonable extrapolation to use the FIT card versus the FOBT. And, I’m okay with that, too.

We do have randomized trials of sigmoidoscopy. What’s a sigmoidoscope? A sigmoidoscope is a way to screen the left side of the colon. There’s a big difference: it’s a shorter scope. It doesn’t go all the way in. The GI [gastrointestinal] doctors will tell you that screening the left side and not the right side is like getting a mammogram on just the left breast, not the right breast.

But, there are a lot of reasons why that’s a false analogy because the left side of the colon is different than the right side. The stool is more solid and the cancers that occur there have different mutations and fundamentally do differently with treatment.

And, because of those differences, some of us believe that sigmoidoscopy actually does work. In fact, sigmoidoscopy has a reduction in colon cancer death. And if you do a meta-analysis of all the studies, there is a small reduction in all-cause death.

So sigmoidoscopy has cleared the highest bar. That might be the only thing I consider doing for myself.

Colonoscopy has always been thought to be–it’s at least a sigmoidoscopy. At least we look that far, and then we look a little bit further. So, it has to be at least as good. That’s the logic.

But, the recent NordICC [Nordic-European Initiative on Colorectal Cancer] Study found that–it’s still early, so it may find a benefit with time–but so far it’s failed to find a reduction in colorectal cancer death from colonoscopy. This is a study that came out of Europe–Norway–and in multiple European countries like Norway, Sweden, and Poland.”

Dr. Prasad on mammography:

“If you look at all-cause mortality in all of the mammographic screening trials put together, you will find there’s just no signal there. It’s just not budging all-cause mortality. It looks pretty null. Confidence intervals crosses[?] one; the actual effect size is like 0.99. It’s as close to just totally null as it gets.

Now, proponents of mammography say, ‘Well, that’s unfair. You don’t have the power to find a difference. I mean, there could be a difference that exists. The studies just aren’t designed and sized for that. And, in fact, we’ve done some power calculations. I had a paper on a few years ago. You’d probably need, like, 3 million women randomized and there are usually in the tens of thousands. Put together, maybe it’s like 300,000, 400,000 women. You need 3 million.

But, the point I want to make is: if you need 3 million women randomized to see the effect, maybe it’s a small effect. I mean, maybe it’s something that might not be worth a $100-billion medical campaign. That’s something that we could think about.

The next thing I’d say is: if you look at just the reduction in death from breast cancer, I always like to separate the trials into this thing you’ve alluded to, which is what we call adequately randomized or suboptimally randomized studies. This is not my nomenclature. This comes from the Cochrane Group–that is the independent research group looking at the studies.

And, it’s exactly as you say: they look for some endpoints that they think are implausible, implausibly related to screening. So, they look at dying from something other than breast cancer. And, if there’s severe imbalances between the two groups, they think there’s something a little bit odd about randomization. And, in fact, that’s true for some of the very older studies.

And I guess listeners may not know this, but in the history of medicine, the first randomized controlled trials came out in the 1940s; and now in 2023, it’s a juggernaut of randomized studies. I mean, we are putting out maybe tens of thousands of random, maybe a hundred thousand randomized studies a year. It’s just a machine. We’ve gotten a lot better at randomization. We used to have envelopes that you would randomize people and open the envelope. Sometimes people would hold them up to the light to try to subvert randomization.

Now we have computer-generated automatic telephone randomization. Pretty much everything about the design and conduct of studies is better today than it was when many of these trials were run–when these mammographic screening trials were run. Many of them use things like Mailer. So, people are invited by mailed invitation to participate in the program. There can be some biases because the group of people who didn’t show up, but the group of people who was assigned to the control arm may include some people who are already deceased, for instance. That’s been cited as a problem with some of these older studies.

This is a little bit long-winded, and so I’ll just cut to the point. The point is that even the biggest optimist about mammographic screening would probably cite a 20% reduction in dying from breast cancer. They can’t claim a reduction in dying for any reason.

And, that means 80% of breast cancer deaths are not avoided. And, this is largely using studies that happened decades ago. And, probably a lot of the changes in breast cancer treatment have eroded that benefit. So, I think that’s what proponents would say.

A critic, like me, would say, is that I truly have no idea if I advise a woman to undergo this screening test if she’s going to live longer. I just don’t know. And I don’t know if she’s going to live better. And, I have to ask myself, what are we doing as a profession that we cannot answer that most basic question?”

These are all reasonable questions to ask. Care, though, does not occur in a vacuum. If a doctor is advising against screening (against the recommendations of medical specialty organizations), and the patient does develop a cancer that causes death, will litigation ensue? Will the family argue that this cancer could have been prevented had the screening test been performed? While the metaphor of turtles, rabbits, and birds makes eminent sense, I suspect it will fall on deaf ears with a jury.

Unless and until the screening recommendations are updated per medical specialty organizations, it will be a bold medico-legal move to persuade a patient that cancer screening is not supported by the data.

What do you think?

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Dr. Jeffrey Segal, Chief Executive Officer and Founder of Medical Justice, is a board-certified neurosurgeon. Dr. Segal is a Fellow of the American College of Surgeons; the American College of Legal Medicine; and the American Association of Neurological Surgeons. He is also a member of the North American Spine Society. In the process of conceiving, funding, developing, and growing Medical Justice, Dr. Segal has established himself as one of the country’s leading authorities on medical malpractice issues, counterclaims, and internet-based assaults on reputation.

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