Patients and their doctors count on cancer screening tests to save lives, and yet a number of large, controlled studies are showing disappointing results for mammography and other mass screening tests. This month, the New England Journal of Medicine published a controversial study that cast doubt on the widely accepted benefits of colonoscopy.
The take-home lesson from these disappointing trials isn’t that we should abandon early screening. It’s still the best hope we have of reducing the high toll of death and suffering caused by cancer — which claims about a half a million lives a year in the US alone.
The right lesson is that saving lives by screening healthy people for cancer is harder than it looks. And within a few years, healthy people will be confronted with newer, more technologically sophisticated blood tests promising to catch more kinds of cancer before it’s too late to cure. While these are a lot easier than colonoscopies or other current screening methods, they’ll probably be introduced as a complement, rather than a replacement.
We need new tools, because our current cancer screening tests are limited. Intuitively, it feels like any test that can spot hidden tumors would save lives and cause little harm beyond some inconvenience and discomfort. But overdiagnosis is an insidious side effect of mammography and thyroid cancer screening because these tests can catch tumors that are so slow-growing they pose no threat. People who discover these tumors can nonetheless suffer stress, additional tests and even sometimes unnecessary chemotherapy and surgery.And yet typical screening procedures may still be inadequate to catch the most aggressive tumors early enough to treat. The good news about the recent colonoscopy study was that overdiagnosis was not a risk. People in the unscreened control group were more likely to be diagnosed with colon cancer — which can lead to chemotherapy or losing a part of your colon. But doctors were disappointed that the death rates were similar for the control group and those invited to get a colonoscopy. (Nonetheless, the fact that this test prevents cancer is a good reason for people to continue to go through it; colonoscopy is not just a test but a chance for doctors to remove pre-cancerous polyps.)
The new blood tests, which are now in clinical trials and could soon be available for general use, aim to address the overdiagnosis problem and the early-detection problem.
These blood tests are sometimes known as liquid biopsies. Though actual biopsies are often done on known tumors, these tests would be performed on both suspected cases and perfectly healthy people. They work on the principle that when people get cancer, some abnormal DNA will be circulating in the blood.
One is being developed by the company Exact Sciences Corp. with the help of Bert Vogelstein, a researcher at Johns Hopkins University who is a longtime leader in cancer research. As Vogelstein explained it to me, this test can analyze blood samples for different kinds of abnormal DNA as well as so-called epigenetic changes — alterations in the molecular packaging surrounding DNA that can suppress or activate different genes.
Those epigenetic changes are the target of another such test, developed by the biotech GRAIL. “More than 70% of the cancers that are killing Americans every year are not detectable by screening,” said oncologist and GRAIL chief medical officer Jeff Venstrom. “There’s a huge unmet need to me as an oncologist. I want to see patients earlier in their disease course when it’s curable.”
That’s where liquid biopsies could make a difference. In a 2020 study published in Science, Vogelstein and colleagues showed that by combining a blood test with CT scanning, they could flag early-stage ovarian and uterine cancers, among others. “That doesn’t nail it shut nor does it show the benefits outweigh the harms, but it’s fair to say it’s promising enough that these blood tests should be pursued,” he said.
GRAIL’s Venstrom says his company’s test actually gives information on the location of the cancer so some patients could get an early warning without being subjected to the radiation exposure of a CT scan. The GRAIL blood test is currently being studied in a 140,000-person clinical trial in the UK, and it’s already available by prescription.
“This field is moving so quickly that we really hope these tests will become standard of care within the next couple of years,” he said — being given to all people over 50 on an annual basis.
The technology is a great advance, but there’s a lot more work to do to know who should get these tests, how often, how much skill is required to interpret the results, and when people still need traditional screening. Only with large, independent clinical trials — like the ones that have moderated our expectations on mammography and colonoscopy — can we learn how to use the old standard and the up-and-coming tests to best help patients.
And the best strategy for patients may not match what’s most profitable for testing companies, doctors and medical centers. The GRAIL test is estimated to cost $949. Critics worry that the cost of annual screenings for everyone over 50 will far exceed money saved by the small fraction of people who have a tumor caught early enough to avoid the most intense treatment. Unless the cost comes down, people may end up paying for it in higher insurance premiums. The tests could be heavily marketed to doctors and their patients — but making the benefits worth the cost might be harder than it looks.
So it’s important to look at the oversized expectations we’ve pinned on our current cancer screenings. We now know that the risks and benefits weren’t completely understood when the tests became the standard of care. There’s always a lot more to learn.