(Image via Pixabay by FotoRichter)

CommonWealth Beacon readers were recently told about exciting developments in screening tests for cancer, the ones that screen a blood sample for molecular markers that suggest the presence of cancer in your body. There are sometimes referred to as MCEDs – multi-cancer early detection tests. Hungry for anything we can do to protect ourselves from our most feared disease, momentum is growing to get these tests approved, though they haven’t been thoroughly studied.

Many, including the companies making them, promise that MCEDs could revolutionize cancer screening. They may. But the experience of two existing screening technologies, mammography and PSA testing, suggest we need to temper our hope with caution. In both cases fear of cancer won out over careful critical thinking as regulators ignored warnings about those unstudied tests, warnings we should have listened to.

Decades of experience using tens of millions of people as unwitting (if willing) research subjects has revealed that these cancer screening technologies save only a small percentage of those screened, and both tests do enormous and serious harm.

In 1973, based on a study claiming that the then-new technology of x-ray mammography led to a 40 percent reduction in breast cancer deaths among the women who were screened compared to women who weren’t – a big relative risk reduction – the American Cancer Society (ACS) pressed the National Cancer Institute to set up the Breast Cancer Detection Demonstration Project (BCDDP). Twenty-nine mammography centers were set up across the United States. But the project had no control group of women who weren’t screened to serve as a comparison, to truly test whether mammography saved lives, and if so, how many. Women would have to be followed for years to get that critical answer. Neither the ACS nor American women were willing to wait.

A few experts urged caution. Dr. John Bailar, a senior official at the National Cancer Institute, re-examined that earlier study and found that only 12 to 14 lives had been saved out of 20,000 women screened, a tiny absolute risk reduction. In a 1976 paper titled “Mammography: A Contrary View,” Bailar wrote, “Promotion of mammography as a general public health measure is premature.” He continued, “I regretfully conclude that there seems to be a possibility that the routine use of mammography in screening asymptomatic women may eventually take almost as many lives as it saves.”

But mammography was instantly wildly popular. Within a year of opening, wait times for mammograms at the 29 BCDDP centers were months long. That popularity helped pressure regulators to formally approve mammography in the US in the late 1980s. Now, hundreds of millions of mammograms later, the evidence has proved Bailar prescient.

Mammography certainly saves lives. But far fewer than commonly believed. And it causes far more harm than is widely known, or that many in the medical community acknowledge.

The respected Cochrane Review, a British nonprofit that provides systematic reviews of the evidence on health care issues, analyzed all the careful randomized clinical trials on mammography and found that if 2,000 women are screened regularly for 10 years:

  • Just one will avoid dying from breast cancer.
  • Two hundred women will experience a frightening false positive.
  • Ten healthy women will be overdiagnosed with ductal carcinoma in situ (DCIS), a type of cancer highly unlikely to ever cause any harm, leading the worried women to undergo clinically unnecessary treatment.

False positives are incredibly common (4 women in 10 aged 50 and up who screen over a decade) and often cause long-lasting emotional damage. And the aggressive treatment of essentially non-threatening DCIS (one in five breast cancers is DCIS, a type of cancer almost unknown before mammography ) often causes physical harm. This includes lasting chest and arm pain (post-mastectomy pain syndrome) in roughly 25 percent of patients.

Mastectomies for overdiagnosed low-grade DCIS cause serious post-surgical infection and breast cellulitis in 4-12 percent of patients. Breast removal commonly involves psychosocial issues connected to female body image. Finally, tragically, one quarter of one percent of women who choose mastectomy for low-grade DCIS are killed by the surgery, the end of a medical cascade that was triggered by mammography.

The story for the PSA test is worse. Men wanted their cancer screening too, so a blood test approved in 1986 only for patients already under care for prostate cancer became so popular as an “off-label” screening tool that it was approved by the FDA in 1994 as a general screening test for healthy men at normal risk. (Some MCEDs are already approved for patients undergoing care.) That was despite known problems with the test’s accuracy, and despite the knowledge back then that many prostate cancers are overdiagnosed, leading to treatment that doesn’t save lives but often causes serious side effects.

Roughly one third of men who have prostatectomies suffer long term erectile dysfunction and/or urinary incontinence or bowel incontinence. Half of one percent who undergo prostatectomy surgery are killed by the procedure.

Experts warned about these risks at the FDA hearing on whether to approve PSA as a screening tool. One said, “There is little evidence that early detection of prostate cancer improves patient outcomes, and there is mounting evidence of the adverse effects of testing and treatment. The lives of millions of American men will be negatively affected.”

And, as a chilling caution that should be heeded by those who will be asked to approve MCEDs, he cautioned that the public’s deep fear of cancer can drive poor approval decisions: “There is a tendency to want to do something to prevent this disease even if there is no proven benefit and even if it means ignoring potential harms. Although this is an understandable viewpoint for advocates of screening, it is not a sound basis for making public policy.”

Beyond the health impacts, the economic cost of the overtreatment of overdiagnosed cancers detected by mammography and PSA tests is enormous. Crude estimates reported in the book I recently authored on cancer risks and fears find that cost to the US health care system was roughly $5.3 billion in 2017. That’s three percent of all cancer care spending annually.

A three-year randomized clinical trial of one type of MCED test is underway in England. More than 140,000 people are being followed. The National Health Service recently reported that they did not find results after the first year “compelling enough to justify proceeding straight away with a large-scale pilot programme of the test in NHS clinical practice, while we await the final results of the trial.”  

But well before that study is done, public demand will certainly increase as word of this new type of cancer screening spreads, promoted by doctors that want to save lives, hyped by simplistic news stories that are far more glowing than cautious, and by the companies developing MCEDs. The economic stakes are enormous. One estimate, assuming approval, is that the global market will be worth more than $32 billion by 2033. The regulators who have to assess whether these tests do more good than harm will face enormous pressure to just say yes.

They would do well to heed the caution of one member of the panel that approved the PSA test when he realized how the vote was going to go. “We cannot, like Pontius Pilate, wash our hands of guilt,” he said. “We must accept the consequences of what we are doing, and that is creating a large number of people…who will be adversely affected in large numbers.”

MCEDs may turn out to be revolutionary in the fight against cancer. Or we may be on the cusp of letting our fear of cancer drive the same mistake again.

David Ropeik is author of Curing Cancerphobia: How Risk, Fear, and Worry Mislead Us.

David Ropeik, a former longtime reporter for WCVB (Channel 5), is a consultant on risk perception, an author, and a former teacher and lecturer at Harvard.