New, experimental blood tests may be a "new frontier" in cancer screening, detecting dozens of cancers typically overlooked by standard tests—but some experts worry these tests may ultimately lead to unnecessary treatments, Gina Kolata writes for the New York Times.

A 'new frontier' in cancer screenings

Currently, standard cancer screening tests are used to detect breast, colon, cervix, and prostate cancers, but 73% of people who die of cancer have cancers that are not detected by these standard tests.

Experimental blood tests, which look for minuscule pieces of cancer proteins or DNA, may be a "new frontier" in cancer screenings, Kolata writes, and they are being prioritized as part of President Joe Biden's Cancer Moonshot program. According to the companies developing these tests, including GRAIL and Exact Sciences, the tests can detect dozens of cancers and could reduce cancer death rates by detecting tumors when they're still small and curable.

In one study, 10,000 female patients ages 65 to 75 in the Geisinger health system were screened using Exact Sciences' test. In total, the blood test identified 26 patients who had different cancers, including lymphoma, breast cancer, lung cancer, and ovarian cancer. Of these patients, 65% had early-stage disease.

In a separate trial of GRAIL's test, which involved 6,629 patients, interim data showed the test detected cancer signals in 92 participants. Of these participants, 29 had cancers that were detected by additional tests, such as CT/PET scans and biopsies. Twenty-three of these participants had new cancers, nine of which were early stage, while six participants previously had cancer and were experiencing a recurrence.

According to Tomasz Beer, a cancer researcher at Oregon Health & Science University who is directing GRAIL's study, a 12-month follow-up of the study participants is forthcoming. "The goal here is to reduce the morbidity and mortality from cancer," he said. "That is a noble and important effort."

"I think there's promise for a real impact," he added.

Does early detection really result in better survival?

Some researchers and cancer experts have been skeptical of the tests' benefits, arguing that early detection of cancer may not necessarily mean better survival outcomes for patients.

"Paradoxical as it may sound, finding cancers earlier could mean just as many deaths, with the same timing as without early diagnosis," Kolata writes. "That is because — at least with current treatments — cancers destined to kill are not necessarily cured if found early."

In addition, some patients may test positive for cancer, but doctors will be unable to locate any tumors. For example, Susan Bell, a 73-year-old nurse who was part of the Geisinger study, initially tested positive for alpha-fetoprotein, which could indicate liver or ovarian cancer. However, a subsequent PET scan and abdominal MRI failed to find a tumor. Currently, it's not clear whether Bell's test was a false positive or if she has a tumor that is too small to detect.

According to Daniel Hayes, a breast cancer researcher at the University of Michigan, situations like Bell's lead to what he calls "Damocles syndrome," since "[y]ou've got this thing hanging over your head, but you don't know what to do about it."

In addition, Susan Domchek, a breast cancer researcher at the University of Pennsylvania, said false positives will become "a real problem" once large numbers of people are being tested. "[W]e need to know what to do with those results and what they mean," she added.

Patients may be at risk of overtreatment with these tests

Another concern with these blood tests is the potential for overdiagnosis, or "finding small tumors that would never have been noticed and may not have caused any harm," Kolata writes.

"Some cancers simply fail to grow or are destroyed by the body's immune system," Kolata writes. "But without knowing if the cancer is dangerous, it will be treated as though it is, subjecting people to therapies that are often difficult or debilitating and may be unnecessary."

According to Barnett Kramer, a member of Lisa Schwartz Foundation for Truth in Medicine and a former director of the National Cancer Institute's division of cancer prevention, overdiagnosis already occurs with standard screening tests, which can lead to thyroid glands, breasts, or prostates being removed for small tumors that end up being harmless.

And with blood tests looking for dozens of cancers, overdiagnosis, and potentially overtreatment, is likely to get even worse. "We will dip more and more deeply into the iceberg of disease" and find "lesions that look like a cancer to the pathologist but may not have the same natural history at all," Kramer said.

Overall, if these blood tests become commonplace without concrete evidence to show they are beneficial to patients, it will be "difficult to unring the bell," Kramer said.

"Everybody loves early detection, but it comes with harms," said Donald Berry, a statistician at MD Anderson Cancer Center. "The harms, we know. The benefits are very uncertain." (Kolata, New York Times, 6/10)