Blood Tests For Cancer

Heart disease is the leading cause of death in the US but I think it’s safe to say that cancer scares us more. Why the second leading cause of death should be scarier than the first is both simple and complex. With both heart disease and cancer there is something invisible, mysterious, and potentially deadly lurking in our bodies. Both diseases tend to take our lives when we are older, and with both, when a young person is struck down, it’s notable, scary, and tragic. (This is all very much in the American context—in many countries people are much more fearful of violence, starvation, cholera, HIV, etc.)

With heart disease, identifying individual risk factors (and mitigating them) makes a huge difference. Cancer is more complicated. “Cancer” really refers to somewhere around a hundred individual diseases, so preventing, detecting, and treating each of them can be quite different. There are a few generalizations we can make about cancer risk factors—tobacco and alcohol cause or contribute to many kinds of cancers, as do poor diet, air pollution, and sun exposure. Additionally, viruses lead to millions of cases of cancer each year, particularly human papillomavirus (HPV) and hepatitis B (HBV), both of which, thankfully, can be prevented through vaccination.

Early detection is one of our best tools in preventing death and debility from cancer. We have tools (of varying effectiveness) for the early detection of colorectal, breast, prostate, and cervical cancers which are among the most common. But we are always looking for better tools, tests that can detect disease earlier and more accurately. Cost-effectiveness is also important, as is convenience. Colonoscopies are very effective at early detection of colon cancer, and can even help prevent it by removing pre-cancerous polyps. But colonoscopy is invasive and expensive, so other tools have been developed, such as testing done on stool samples. All of these have advantages and disadvantages.

One test patients have started asking me about is called “Shield” which uses a blood sample to test for DNA fragments in the blood that are seen in people with colon cancer.¹ This test has an enormous potential advantage over other tests—it doesn’t require packaging up a stool sample; it doesn’t require preparing for and taking time off for a colonoscopy. Unfortunately, it also isn’t terribly accurate—it’s fairly sensitive for detecting cancers, but not for detecting precancerous polyps. It’s overall sensitivity just isn’t that good, and not as good as the Cologuard stool test currently in use. (And of course none of these tests is as good as a colonoscopy). At this point, despite FDA approval, I don’t think Shield is a tool that’s ready for broad implementation. I could see using it if someone wants screening but won’t do a stool test or colonoscopy, but if it’s positive you have to be willing to follow it up with a colonoscopy.

While I’m not yet ready to recommend blood tests for colon cancer, I suspect we will be using it in the not-too-distant future. I also think the future will bring us similar blood tests for other cancers. The “cell free DNA (cfDNA)” technology these tests use hold a lot of promise. One, called “Galleri”, is already on the market, although it is not yet FDA-approved. Over in the UK an enormous study is underway to evaluate this specific blood test.² This is not without controversy though.³ Many experts believe that this large-scale trial isn’t justified. The test did not perform well in earlier trials, certainly not well-enough to justify using it here in the US.⁴

These so-called “liquid biopsies” (a terrible name) have a lot of promise. The basic premise—that tumors will release detectable fragments of DNA into the blood—is sound. What is lacking so far is evidence that these tests actually detect enough cancers at an early enough stage to matter. While there are huge obvious advantages to screening for cancers with blood tests, we just aren’t there yet.

Stay well.

-pal

1  Lo, YM D. "Cell-Free DNA for Colorectal Cancer Screening." The New England journal of medicine 390.11 (2024): 1047-50. DOI: 10.1056/NEJMoa2304714.

2  Neal, R. D., Johnson, P., Clarke, C. A., Hamilton, S. A., Zhang, N., Kumar, H., Swanton, C., & Sasieni, P. (2022). Cell-Free DNA–Based Multi-Cancer Early Detection Test in an Asymptomatic Screening Population (NHS-Galleri): Design of a Pragmatic, Prospective Randomised Controlled Trial. Cancers, 14(19), 4818. https://doi.org/10.3390/cancers14194818

3  McCartney M, Cohen D. Galleri promises to detect multiple cancers—but new evidence casts doubt on this much hyped blood test BMJ 2024; 386 :q1706 doi:10.1136/bmj.q1706

4  Liu MC, Oxnard GR, Klein EA, Swanton C, Seiden MV; CCGA Consortium. Sensitive and specific multi-cancer detection and localization using methylation signatures in cell-free DNA. Ann Oncol. 2020 Jun;31(6):745-759. doi: 10.1016/j.annonc.2020.02.011. Epub 2020 Mar 30. PMID: 33506766; PMCID: PMC8274402.