Tests that screen for dozens of cancers using just a single vial of your blood—it sounds miraculous. Biotechnology startups are developing such tests, which look for bits of mutated DNA shed by cancers and aim for cancer to be diagnosed at its earliest stages, when there is a higher chance of cure.
Genetic tests for cancer have also become big businesses. The developer of one such test, Grail, was acquired by Illumina in August for $7 billion. Another company, Thrive Earlier Detection Corp., was acquired by Exact Sciences a year ago for more than $2 billion. And there’s strong evidence that the tests will work: While they have yet to be approved by the Food and Drug Administration, similar technology has already been approved for people previously diagnosed with cancer. Peer-reviewed articles show that the concept is scientifically valid. For people who don’t mind paying $949 out of pocket (and trying something that isn’t yet FDA approved) Grail’s test, Galleri, is already available by prescription.
One thing you should know, though: There are many ways exuberant cancer screenings can actually end up harming our health and well-being.
The pitfalls of too much cancer screening are well understood. While we do not exactly know how these particular tests, which can screen for up to 50 cancers, will perform in the real world, they give me, a radiation oncologist, pause. Millions of patients are screened for cancer each year, with countless mammograms, Pap smears, colonoscopies, blood tests, and CT scans. Drawing on the lessons researchers, patients, and doctors have learned from these screenings, I came up with the Five Laws of Cancer Screening. These show how multicancer screening technology isn’t automatically a good thing, and that it should be wielded carefully.
1. Tests tend to be best at finding the cancers that are the least likely to kill you.
You might think that having cancer is automatically bad, but the reality is that sometimes cancer is harmless. Cancers have to grow to a certain point before they are large enough to causes symptoms, like pain, or interfere with how an organ works. A cancer that is one cubic centimeter in size has about 100 million cells but is still too small to cause symptoms in most cases.
The slowest-spreading cancers have a long window when they are detectable but not causing symptoms. This window makes them easy to pick up on screening tests. Many of these cancers will actually never go on to cause symptoms—and we can’t tell which ones will progress. This leads to essentially an overdiagnosis of problematic cancers.
How common are asymptomatic cancers? Autopsies have shown that if men live long enough, about 60 percent develop prostate cancer, but American men only have about a 2 percent chance of dying of prostate cancer. The vast majority of men with prostate cancer detected by prostate-specific antigen screening have no symptoms from their cancer at all.
The prostate is the organ with the highest percentage of asymptomatic cancers, but they occur in other sites as well. Ductal carcinoma in situ is a noninvasive growth of breast duct cells. It is a risk factor for developing invasive breast cancer, but it cannot spread unless it transforms into invasive cancer. DCIS is almost always asymptomatic and was rarely diagnosed prior to mammography. Now about 50,000 American women are diagnosed with DCIS each year. Treatment for DCIS is similar to that of invasive breast cancer, with many women receiving surgery, radiation, and endocrine medications. These treatments prevent some women from developing invasive breast cancer, but they all have side effects, and when deployed against DCIS, they have not been shown to improve life expectancy.
2. No test is perfect.
Even tests with high specificity result in lots of false positives when they are used on people with a low risk of having the disease in the first place. Put simply, if you test enough people, even a small rate of false positives starts to add up. One study on mammography predicted that if 1,000 women had an annual mammogram for 30 years, eight lives would be saved, but there would be 2,250 false positive mammogram results. On average, that’s more than two for every woman! Each false positive results in extra tests, like additional imaging and biopsies. They also cause psychological harm to patients’ well-being.
To date, companies offering multicancer screenings have reported little about how often their tests return a false positive or an inconclusive result. Even if the rate of false positives is lower than traditional screening tests, which look for one kind of cancer at a time, testing for so many cancers may dramatically increase the number of false positives patients receive. Additionally, inconclusive or false results on a multicancer screen may be pretty unsettling, as the test could just indicate that cancer is present somewhere in the body. If a person is told, “You have cancer, but we don’t know where,” it may lead to a prolonged search with multiple scans and multiple biopsies.
3. Testing early moves the goal posts.
Cancer can be detectable 10 years or more before it causes symptoms. While this may sound like a good thing—lots of time to find it!—the side effects of treatment often start immediately. Multicancer tests screen for some cancers that require procedures with life-changing effects, like the surgery needed to cure pancreatic cancer. After this surgery, 40 percent of patients have a serious postoperative complication, 50 percent have livelong digestive problems, and 10 percent develop diabetes. Screening will move the morbidity from similar procedures into years when people would have been healthy.
Yes, you can delay treatment. People who chose not to treat cancer avoid the side effects of treatment, but they often have psychological harm from the knowledge that they have cancer. They may second-guess their decision or overestimate the risk of progression. Screening for 50 cancers not only increases the risk of this happening, but it increases the possibility of each patient having to deal with multiple cancer diagnoses.
4. “Shared decision-making” is a fiction.
Many studies of cancer screening call for physicians and patients to have a detailed discussion about the risks and benefits of screening. In practice, this is rarely done. People have difficulty balancing the risks and benefits of multiple uncommon events. No cancer screening test has consistently shown that it improves life expectancy, although patients often don’t believe this. Discussing the potential negative consequences of a single screening test is complex and time-consuming. Discussing the possibilities when screening for 50 cancers borders on the impossible. Instead, patients may end up having screening with little thought given to the consequences.
5. Not all preventive care saves money.
The U.S. spends more than $200 billion each year on cancer. Cancer treatment is expensive, and the costs of additional treatments due to multicancer screening tests—including unnecessary treatments—will not be borne by Illumina or Exact Sciences, but by American citizens.
Ignorance may be bliss—especially in the face of information that does not stand to be useful to you—but few people choose it when it comes to their health. I worry that the success of these companies will enrich their founders and investors but will saddle society with increased health care costs. Side effects and anxiety will creep into years when people would have been healthy. This decrease in our well-being will be done for a modest improvement in cancer mortality. And cancer is far from the only thing you can die of: With so many other fatal diseases, like heart disease, stroke, dementia, and diabetes, these tests are unlikely to significantly improve our life expectancy.
The broadness of genetic multicancer screening tests makes it difficult to define a population that they would benefit most. In order to realize the potential of these tests, we need a better understanding of which cancers will progress and treatments that have less toxicity. Until these goals have been accomplished, multicancer screening tests may inflict more fear and suffering than they relieve.