Liquid Biopsy – Debate Over Early Detection Through Blood Tests Continues to Grow

Cancer is a group of life-threatening diseases that can be completely treated through early diagnosis. However, we are not yet where we want to be in the early detection of many cancers. Technologies developed in recent years have improved the possibilities. Liquid biopsy is one such technology, enabling cancer cells to be identified and monitored through a blood test. Galleri is the liquid biopsy test most widely known worldwide for early cancer detection. By enabling early detection of 50 cancer types, it may help treat disease sooner. However, liquid biopsy technology, which has not yet received FDA (US Food and Drug Administration) approval for "early cancer detection," also carries the risk of misleading results. Its use therefore requires a cautious approach.

Anthony Arenz, a 51-year-old firefighter living in Mesa, Arizona, breathed a sigh of relief after a negative Galleri blood test screening for 50 cancer types. This was excellent news for a firefighter whose occupation gives him a cancer risk 9% higher and a risk of cancer death more than 14% higher than the average person.

In the following days, Mesa invited firefighters over 50 for free health screening, including whole-body MRI (magnetic resonance imaging). Trusting his negative Galleri tests, Arenz did not want to spend more time on screening. Still, remembering colleagues who had died of cancer over the past 3 years, he gave in to his anxiety. They had been 10 years younger than him. If only they had had access to such free screening, perhaps things could have been different. He began researching and found a statement on the Galleri website that negative results such as "no cancer signal detected" still did not reduce the risk of cancer to zero.

Although Arenz wanted to believe the blood test result, anxiety about losing younger colleagues led him to accept the free screening and schedule an MRI. The results disappointed him. Unfortunately, the Galleri blood test had not told the truth. Arenz had stage-1 kidney cancer.

Can a Negative Liquid Biopsy Result Provide Reassurance?

The blood test's ability to detect cancer—and perhaps most importantly, its incorrect results—has been under scrutiny from the beginning. How it produces false results in practice, how many, and how frequently are not yet widely understood. The test has also not yet been approved by the FDA (US Food and Drug Administration).

Dr. Vershalee Shukla, a radiation oncologist and co-founder of Vincere Cancer Center, which provides free health screening for Mesa firefighters, emphasizes that cancer screening is a very complex issue .

"To be honest, the tests are good, but they are not ready yet for broader use."

A Positive Test Result Should Not Immediately Alarm You

Arenz was not the only firefighter disappointed by a blood test result. Mike Curtis, 51, who has been a firefighter since 17, also knows he is at risk of cancer. His father, also a firefighter, died of cancer at 58. Yet Curtis was not particularly worried because his health screening had been clear. A subsequent Galleri blood test shocked him: it was positive and had detected signs of cancer.

The positive blood test despite negative health screening made Dr. Shukla suspicious. To be certain, she ordered an abdominal and pelvic PET-CT scan. She was right: Curtis did not have cancer. Galleri had once again produced an incorrect result and caused anxiety.

What Do the Galleri Blood Test Data Show?

Dr. Shukla says that 18 months after adding the blood test to screening, only 1 of 2000 screenings had a false-positive result (a positive result when cancer was not actually present). The test correctly identified 2 people with cancer: one with chordoma, a rare bone cancer, and another with head and neck squamous cell cancer. Galleri's very early detection of both cases allowed early treatment.

However, there were 28 false negatives (negative results when cancer was actually present), suggesting poor sensitivity for detecting cancer. Another 500 tests have not yet been verified, so the figure of 28 will probably be higher. This is a terrible result. Scientists believe the test gives people a misleading impression of whether they have cancer.

Dr. Shukla: "It creates a major false sense of security. On the other hand, chasing cancer—especially cancer that isn't there—can be extremely frustrating and expensive."

Dr. Whitney Jones, an executive at Grail Medical, says the company's overall goal is to offer a sensitive test that accurately detects the most dangerous cancers and complements other health screenings rather than replacing them . Test sensitivity can also vary by cancer type.  

According to Prof. Ji-Hyun Lee of the University of Florida Health Cancer Center, who reviewed Grail's public data and Dr. Shukla's data, the results are "a little frightening." These results show how much confidence people should place in the likelihood of a correct test result. How worried should they be by a positive result, or how reassured by a negative one?

Only half of the positive predictions in Dr. Shukla's data were confirmed, while the figure in Grail's data was 38% (35 of 92 tests were correct). Such error rates, although there was no particular threshold, "do not inspire much confidence in the test's accuracy" , Dr. Lee said.

"In a clinical setting, positive predictive value is more useful for making decisions for a patient. It is not always high, because things do not always translate perfectly into the clinic. But if only 38% of people in the general population with positive Galleri results actually have cancer, the test is not very useful for patient or physician decision-making."

Dr. Electra Paskett, an epidemiologist and cancer screening expert at Ohio State University, emphasized that both false-positive and false-negative tests carry a range of costs for people. "If the test is going to be recommended to someone, I think everything needs to be more than completely clear."

Why Is the Galleri Blood Test Still Used in the US?

According to Dr. Shukla, today's data are important for making the test much more effective in the future. Specialists, physicians, and most importantly patients need tests like this that can diagnose cancer quickly and early. Nevertheless, Grail needs data from groups at much higher cancer risk—even higher than firefighters—to improve the test.

Neither Curtis nor Arenz regrets taking the test. Curtis said that thinking he had cancer, even for a few days, had not carried a very high emotional cost. He acknowledged that things would of course have been different if he had paid for it. Arenz emphasized that his colleagues should not neglect additional health screenings.

Dr. Shukla: "Every medical center offering this test must be very careful. It is not that simple."