It was a typical overcast morning in the San Francisco Bay area as both of us, who are doctors: Rahul, a pediatrician, and Jonathan, a diagnostic radiologist, headed to work.
As Rahul strolled through the parking lot, another day of patients to see in his office, he was notified of a medical test result by a phone push notification. The app took its sweet time loading as it connected him to his medical record. A few days earlier, he had seen his doctor for a routine checkup. The bundle of tests was ordered algorithmically by his doctor. One-by-one, he scrolled through them.
Blood count, normal; electrolytes, normal; cholesterol: normal
Prostate Specific Antigen, elevated.
Rahul stopped strolling, his eyebrows shot up. He blinked and stared back at his phone. He hustled toward his office and logged into his workstation. He pulled up his schedule for the day along with searches on Google and on Medline, trying to recall from medical school decades ago what a slightly elevated PSA test—a biomarker of potential cancer—meant.
Was it really elevated? It depended on his age, right? Would he need an invasive biopsy? Should he ignore the result? And most importantly: Did he have cancer? Rahul’s doctor told him they would repeat the test in three weeks. It came back normal. The next time he tested it was slightly elevated again. A fourth test brought the same result.
Read more: “It’s the Secret Doctors Keep from You”
Rahul continued to read about the PSA test. Medical consensus once recommended that every man over 50, as Rahul was, should have the test. That was now softened to screening after a conversation between the patient and doctor. Some experts suggested that regular screening be dropped altogether. The potential harms of treatment might outweigh the benefits, as it turned out, and many men who had prostate cancer ended up dying of something else, the cancer growing so slowly that it never caused a problem.
Rahul’s doctor didn’t talk him through these facts. He didn’t even tell Rahul he was ordering the test. Rahul was in a pickle. Now that his PSA was abnormal, should he go down the road of invasive biopsy? Should he just ignore it? It felt unfair to have to make these choices. He just wanted to know. He just wanted to feel certain of what he should do. The fact that nobody could provide him with that certainty was frustrating and frightening. The whole thing just seemed so … stupid.
Did it have to be this way? Could Rahul, or any patient, ever feel certain?
To answer, let us explain what screening tests—and cancer screening tests, in particular—are all about. Maybe then we can all get closer to understanding one of the most critical issues in medicine.
When Screening Does Harm
Medical tests come in two major varieties, The first is symptomatic testing, which is ordered based on your individual medical complaints, physical exam, or other indications that a disease is present. If you have a fever and a hacking cough, your doctor may order a chest X-ray to see if you have pneumonia. If you have morning nausea or a missed period, your OB-GYN may order a pregnancy test.
The second category is asymptomatic testing—screening—which is performed to diagnose various diseases and conditions in a population susceptible to risk, who have no current indications of disease: no pain, discomfort, or any abnormal signs. Everyone within the defined population is encouraged to get tested. Examples of this include mammograms for breast cancer on women over 40, and colorectal screening for colon cancer for people over 45.
If symptomatic testing is like the highway patrol pulling someone over because they are driving erratically, then an asymptomatic screening test is like a random sobriety checkpoint on New Year’s Eve. The former is done because of a specific issue (a driver can’t stay in his lane) and the latter is a general search in a population where the risk is high (anyone driving after midnight on New Year’s Eve).
When it comes to cancer, a good screening test is one that allows early detection before patients develop symptoms, has an effective treatment associated with it, and has a favorable balance of risks, harms, and benefits. And when screening helps people find cancer early and get cured, medicine’s mission has been accomplished.
For every triumph, though, there are many like Rahul’s, where cancer screening leads them down a rabbit hole of uncertainty toward further, often intrusive and nerve-wracking procedures. There are still others where the screening test is negative, but patients later learn that the tests were wrong. The cancer is detected only later, when it’s already harder to treat.
The first lesson is that a positive screening test for cancer does not necessarily mean a patient has cancer. But that result does trigger additional testing to better determine what is really going on. And that’s where the slope gets slippery.
One of the most persistent harms of screening is overdiagnosis, where we catch cancer that would never have affected the individual. This goes against our instincts, which tell us that if we have cancer, it should be caught and treated no matter what. But in fact, especially as we age and other causes of death become more common, we can often live with a slow-growing cancer that never really has other repercussions for our health. By performing autopsies on men who died from some other cause, for example, we find that a large proportion of them had prostate cancer and never knew it, and it likely didn’t shorten their lifespan.
Overdiagnosis due to screening carries significant risks. A high incidence of men with elevated PSAs who go on to get treatment—biopsies, surgery, radiation, hormone therapy—suffer complications that include long-term urinary or bowel incontinence, erectile dysfunction, and higher rates of bladder cancer.
The truth is, we don’t always have a way of knowing which cancer will lead to death, and which can be ignored or watched until it causes a problem. And even if we did have a way of differentiating, it’s very hard for a patient to hear they have cancer, but not do anything about it. Sometimes the best answer—as hard as it is to accept—is to not test for cancer at all.
South Korean physicians and patients learned this the hard way. As a result of national health insurance, patients could be screened for common cancers like breast and colon for free. Beginning in 1999, for a small copayment, they could also receive neck ultrasound screening for thyroid cancer. Soon after, the nation found itself engulfed in an epidemic of thyroid cancer.
Suddenly, people had to decide whether to have their thyroids cut out, which would mean a life sentence of thyroid replacement medication and regular thyroid blood tests for the remainders of their lives. Many who got the surgery also learned they were afflicted by a deficiency in parathyroid hormone, which is produced by a small gland on the underside of the thyroid, often removed during thyroidectomy.
After the screening campaign, the number of people diagnosed with thyroid cancer went up 15-fold. Despite this spike, mortality did not change. Each year, before and after the screening campaign began, 300 to 400 people died of thyroid cancer in the country. By 2014, doctors and public health advocates were starting to speak up and question whether thyroid cancer screening was leading to overdiagnosis and overtreatment. In 2015, the government-funded National Cancer Center Korea changed its guidelines to recommend against thyroid screening.
Read more: “Why Reading Your Doctor’s Notes Can Be Painful”
The Radiologist’s View of Breast Scans
Why can’t doctors tell which positive results are real, and which ones are false alarms? And even when a cancer is real, why can’t they tell whether it will cause life-altering trouble down the line? Let’s consider the breast cancer screening path.
On a typical day, Jonathan sits down to read 100 to 200 screening mammograms. A completely normal exam might take two to three minutes—two views of each breast, magnifying every part of each one. If Jonathan sees something he can’t convince himself is normal, then the exam is “positive,” and he and his team ask the patient to return for more imaging. About 10 percent of screening patients get called back. Too many more, and the physicians are probably being too sensitive. Dip under that 10 percent threshold, and the physicians may begin to worry that they are missing things. Federal law requires radiologists to track these and other numbers, keeping them accountable.
The problem with cancer is that it doesn’t know when to stop growing and doesn’t respect normal boundaries, so it classically looks like the shadow of a mass with spiky edges, surrounded by distorted tissue or other secondary findings. One finding doctors look for is “microcalcifications”—little bits of calcium that appear bright white on a mammogram. In some forms, these blobs look a lot like the after-effects of the cancer, similar to burn scars after a fire—irregular, ragged, the visible residue of a cancerous process. But cancer doesn’t always announce itself that way. Some microcalcifications are just small clusters of innocent-appearing dots yet still represent cancer. Harmless-looking and harmless don’t always go together. Wouldn’t it be great if they did.
We manage this uncertainty by creating thresholds for who we call back. The rules are designed to catch as many cancers as possible, while not calling too many patients back unnecessarily. When it comes to calcifications, number, newness, shape, and groupings are the criteria. If a calcification meets the threshold, Jonathan calls for more imaging with even greater magnification, knowing most won’t be cancer. We could magnify everything upfront and get a closer look from the start, but that’s more radiation, more resources, more time. About 40 million mammograms are performed annually in the United States, so doubling the time required for each exam would come at a significant cost. We accept that some women will be called back unnecessarily, because the alternative costs more than it saves.
Jonathan also knows that among the cases he reads every day, there are cancers he is missing. Three dots of calcium instead of five don’t make the cut. Others he just doesn’t see or are obscured by normal tissues. The line between normal and abnormal is genuinely thin, and the system is designed with that knowledge, balancing the harm of missing cancers against the harm of calling back too many healthy people. But it’s still Jonathan making that call, case by case. He follows the rules and feels the weight of that.
When radiologists call patients back and do more imaging, they still aren’t diagnosing cancer, they’re just making the next decision in the process, in this case determining what needs a biopsy. They’re fairly certain some things are cancer or benign. But there’s a zone in between—an overlapping Venn diagram of appearances—where a physician can’t reach the threshold of certainty either way. So, they take a tissue sample and look under the microscope.
Microcalcifications don’t always represent invasive cancer, which always requires treatment, they are often due to ductal carcinoma in situ or DCIS. One way to think of DCIS is as “stage zero” breast cancer—cancer cells still nicely confined within the milk duct. A bad character, for sure, but still behaving itself, even if it’s growing. There is discussion about how to characterize it for the lay public—early cancer? Pre-cancer? Not cancer at all? But that’s just branding. Whatever we call it, there’s a really important feature of DCIS: Sometimes it will affect a patient’s life, and sometimes it won’t.
We know this because of autopsy studies. Nearly 1 in 11 women who died of other causes were found to have DCIS that had never bothered them—clinically undetected and irrelevant during their lifetime. And yet, left untreated, somewhere between 10 percent and 50 percent of DCIS cases would eventually progress to invasive cancer. The problem is that we just can’t tell which ones. We haven’t found a reliable marker—genetic, morphological, or otherwise—to foretell the future, and instead we treat them all, knowing we are overtreating some. The ones who never needed treatment, these are the ones we call “overdiagnosis.” But which ones are they?
Medicine is actively trying to solve this puzzle. Four international trials are currently evaluating whether low-risk DCIS can be safely watched rather than surgically removed. And when the results are found, checked, and confirmed, there may be new guidelines for when to follow and when to treat DCIS.
We do our best to balance the harms, risks, and benefits for breast cancer and every cancer in a screening program, but we must set some rules and guidelines, and that makes the screening tests and programs imperfect. For every line we draw, someone will be caught on just the wrong side of that line, and the system will fail them.
Making Peace with Uncertainty
Even with the best evidence, screening programs clash with the harsh reality of the real world. After all, tests only work if patients receive them. As most of us know, colonoscopy as a screening tool for colon cancer is no fun. It requires us to stop eating and drinking and instead drink uncomfortable prep cocktails of electrolytes to clear our bowels. It requires sedation, with its associated risks, and has a non-zero chance of a complication like bowel perforation. It requires a procedure room and special equipment, which may not be available in the numbers required to serve large populations across a nation.
When the technology is available, some people still say, “No, thank you.” In 2000, only 29 percent of eligible patients screened for colon cancer by colonoscopy. Women are also opting out of mammograms. A 2024 study out of the University of California, Davis—the biggest of its kind, tracking 3.5 million mammograms across 1 million women—looked at what women did after getting a false positive test. A woman who got called back for a scare that turned out to be nothing was less likely to come back for her next mammogram. The more the system put her through—the repeat imaging, the anxious six-month wait to “keep an eye on it”—the less likely she was to return.
This need for individual attention and the search for certainty that is lacking in population-level screening has opened the door for another type of screening, designed and marketed under a different moniker.
For a few thousand dollars, otherwise healthy-feeling people can have a full-body MRI scan, nouveau bloodwork, or other tests to look for disease lurking in their bodies. The promise—a seductive one—is that of certainty, something that your regular doctor cannot give you. It doesn’t feel like the screening we know, and it’s typically not sold that way; it’s marketed as wellness, as a proactive choice, something fundamental to do for your health and future.
But the challenges of screening can’t be avoided: There will be overdiagnosis, blind spots leading to a false sense of security, additional cost and pain. People will go get additional tests and surgeries, only to find nothing. There will be sleepless nights.
One healthy 35-year-old man from New York experienced this when in 2023 he paid $2,500 for a full-body MRI endorsed by Kim Kardashian as “life saving.” The test was negative: all clear. Eight months later he collapsed due to a catastrophic stroke, the consequence of a blocked artery, allegedly visible in that full body MRI. Now partially paralyzed, he has filed a lawsuit against Prenuvo, the whole-body scan provider, claiming the blockage should not have been missed. (The radiologist working with Prenuvo, who reviewed the scan, previously had his medical license suspended in connection with an auto insurance scheme in which he was accused of falsifying findings on MRI scans, reported Ars Technica.) Despite what the suit claims, it’s also possible the arterial stenosis was not visible on MRI, as the protocol for these screening exams is not the same one we use to evaluate arteries. It’s in details like this where direct-to-consumer use of medical technology can fall short. The screening tests we offer, while far from perfect, are carefully thought out by experts with the best intentions. In contrast, the full-body MRI you can pay for is untamed, without any focus or rigor needed to go from a diagnosis to cure.
But screening can work, if it’s based on the evidence and careful thought and planning. When programs are designed around how people behave, for example, the results can be transformational.
Read more: “When Did I Start Getting Cancer?”
Our colleague, T.R. Levin, a gastroenterologist, began mailing FIT kits to screen eligible people in our Northern California healthcare system for colon cancer. The kits contain a small vial into which patients can insert a small sample of their stool and mail it back to a lab for analysis. Levin told us screening rates in the healthcare system climbed from 39 percent in 2000 to nearly 83 percent in 2015. (The Journal of American Medical Association has also reported that FIT kits increase individual testing and lower the risk of dying from colon cancer.) A similar approach, home or self-collection, has been adopted and is spreading to screen women for cervical cancer.
So, how do we navigate this sea of population health, statistics, and confusing testing?
As doctors, we need to be more thoughtful and invest more of ourselves in how we approach and explain screening. We cannot screen simply to meet a metric without engaging patients with better conversations and understanding. We may not be able to give patients certainty, but we can certainly try to give them clarity.
As medical professionals, as a society, we don’t know all the answers. But we know one thing: A lack of clarity, a lack of certainty, can make things seem stupid. The system is not stupid. The science is not stupid. The real problem is expecting certainty when certainty was never on the menu to begin with.
Because when we can’t accept that, or don’t understand it, then we go looking for whoever promises a clean answer. And there is always someone willing to make that promise.
Instead, doctors can offer clarity—of what’s happening, what the options are, what the odds are. A positive screening test does not necessarily mean you have cancer. So, let’s talk about what to do if your next test is positive. Consenting to screening must come from thoughtful conversation, not just an algorithm. And patients, in turn, must be willing to meet doctors there, accepting that clarity, not certainty, is what medicine can offer.
After further thought and conversation with his family, Rahul recognized he owed it to them to figure this out. A urology consult helped him define his next steps. An ultrasound was normal; more detailed blood testing awaits. An MRI remains a possibility, as does a biopsy, should he and his doctor agree it’s needed.
And yes, that clarity feels a lot less stupid. 
Lead image: Tasnuva Elahi; with images by zlikovec and CreativeArtnest / Adobe Stock
