As I get more primary care visits under my belt in this first year of residency, I’m coming to appreciate just how tricky a topic cancer screening can be. Being able to clearly communicate to patients the risks and benefits of colonoscopies, mammograms and other types of screenings  is an art. 

In today’s Research Corner, I explain why those conversations could soon get even trickier.

How a Cancer-Screening Blood Test Could Backfire

Earlier this year, federal lawmakers introduced House and Senate bills that would force Medicare to consider covering a controversial new type of cancer screening test that looks for early signs of disease in a person’s blood. 

Given that cancer still takes more than 600,000 lives in the U.S. each year, a better screening tool has obvious appeal.

But a review of the evidence behind this new testing technology recently published in JAMA Internal Medicine raises important questions about its readiness for primetime. 

In their review article, physicians David Carr and H. Gilbert Welch raise two important questions about this new screening tool known as a multi-cancer early detection (MCED or MCD) test:

1) Does this new test catch cancer early and often enough?

MCED tests are part of a larger category of blood tests known as liquid biopsies that scour a person’s blood for tumor cells or other early signs of cancer. 

The technology cannot diagnose cancer — it can only alert a clinician that cancer is likely present and suggest where in the body it might be found. 

One big problem, write Carr and Welch, is that these tests miss the mark a lot of the time.

In two separate demonstrations of MCED tests from biotech firms Grail and Exact Sciences, the technology caught less than 1 out of every 3 cases of cancer. On the flipside, in one of those two trials, 62% of the cases flagged by the MCED assay as likely cancerous could not be confirmed as malignant after all.

False alarms are common with other types of cancer screening, too, but they may be especially problematic for MCED tests, which look for multiple kinds of cancer and can therefore require more comprehensive follow-up testing to investigate a positive result. 

Other research shows this kind of follow-up testing can lead to anxiety, out-of-pocket costs and medical risks like radiation exposure or medical complications. The dangers of false alerts loom especially large when you go hunting (i.e. screening) for a relatively rare disease in a population as big as, let’s say, “everyone on Medicare,” or “all adults.”

2) Does the technology’s possible benefit outweigh its potential harms?

Even if these tests get better at catching more cancers at an early stage, would doing so actually improve a patient’s outcome? Would it extend the patient’s life? 

Maybe not, the authors of the research review suggest. Stronger evidence of this technology’s benefits is needed, Carr and Welch say.

“If you’re claiming that there’s a benefit to screening for a huge percentage of cancers with these liquid biopsies, there’s an obligation to follow that up with evidence,” Carr told me. 

There are at least two research trials underway to help answer these questions. One out of England will measure the impact of MCED screening on late-stage cancer diagnoses. Another, run by the National Institutes of Health in the U.S. and set to begin in 2024, will measure whether the use of MCED tests reduces the number of cancer deaths. 

There’s one other question that clinical trials alone can’t answer — and that’s whether this new technology is worth its cost. These tests currently go for about $900 a pop out of pocket — not including the costs for potential follow-up testing. The technology could easily run up the tab of an insurer like Medicare by billions of dollars a year.

Regulators may soon raise the bar for new diagnostic tests 

With his Cancer Moonshot initiative, President Biden has vowed to “fundamentally transform how we prevent, detect and treat cancer.” And I admire executives like Josh Ofman, president of the MCED test maker Grail, who told me, “We’re losing thousands of our loved ones each day to cancer and need new tools desperately,” for going after these lofty goals. 

But there are also real harms and costs to letting our hunger for innovation get ahead of the evidence.

The Food and Drug Administration appears to share that concern. On Sept. 29, the agency proposed tighter regulatory standards for this new generation of diagnostic tests.

Personally, I know I’d appreciate more clarity from regulators around the proper use of MCEDs before I start regularly screening my patients with them. 

Tradeoffs’ coverage of diagnostic excellence is funded in part by the Gordon and Betty Moore Foundation.