'Liquid Biopsy' Holds Promise of Detecting Deadly Cancers Early

Silicon Valley tech-start-up and venture capital lawyer Roger Royse wanted to do all he could to stay healthy. Royse's father battled stomach cancer at 69, and although the younger Royse had no symptoms, at 64, he was mindful of cancer risks. When he read about a new "liquid biopsy" test that may detect up to 50 different cancers — including the deadliest ones — from a single blood sample, he was intrigued.

"Mostly, I was just checking boxes," Royse recalled from his Palo Alto, California, office. "I was 99.9% sure nothing would pop up."

About two weeks after paying almost $1,000 out of pocket and providing a blood sample for the "Galleri" test, its creator, biotechnology company Grail, alerted Royse that it had detected two "cancer signals" in his blood: one for pancreatic or gall bladder cancer, and the second for stomach or esophageal cancer. An MRI then detected a mass that an oncologist quickly determined was Stage 2 pancreatic cancer, one of the deadliest forms of the disease.

"One thing is certain: I caught it just in time," Royse said about his cancer diagnosis. "The Galleri test absolutely saved my life."

U.S. cancer deaths have fallen by one-third in the past 30 years, but the disease remains the country's second-leading killer, taking the lives of more than 600,000 annually. That's driven by 12 cancers that cause more than 75% of all deaths, according to the National Cancer Institute (NCI).

Only five of those cancers have widely recommended screening tests: breast, cervical, colon, lung and prostate. That leaves seven — melanoma (skin), bladder, non-Hodgkin lymphoma, kidney, leukemia (blood), pancreas and thyroid — for which there are no broadly accepted screenings before a patient has symptoms, at which point the disease is more advanced, more difficult to treat and deadlier.

Other cancers with disproportionately high death rates, but no widely recognized screening tests include: liver, brain/nervous system, esophagus and ovarian, NCI data show. (The NCI, however, notes that several of these cancers do not currently have effective treatment options, so detecting them early may not benefit patients in the long run.)

Advancing age is the single biggest risk factor for developing cancer, according to the NCI. More than nine out of 10 cancers diagnosed in the United States are in people 45 and older, and the median age at the time of a cancer diagnosis is 66.

These factors have driven the quest for "multicancer early detection" (MCED) tests, nicknamed "liquid biopsies." These tests look at a patient's blood sample for bio-markers — biological substances or anomalies — that may signal the presence of cancer. If the test detects a marker, the technology may then be able to assess from where in the body it originated.

The tests' long-term promise is that they can detect, at an early stage, multiple types of cancer from an easy-to-administer blood draw. But some clinicians caution that the tests have not yet been subjected to rigorous scientific studies to determine their accuracy and effectiveness, and whether they lead to an overall decrease in cancer deaths.

"There's not been sufficient long-term data to really show that use of these multicancer early detection tests, in fact, improve patient outcomes," said Lori Minasian, a board-certified medical oncologist and deputy director for the NCI's Division of Cancer Prevention. The institute this year is launching a pilot that will begin to comprehensively investigate the tests, initially in people 45 to 70.

"We're excited about the technology," Minasian said. "We just want to study it rigorously so that we know how to best use it."

MCED tests created by three companies have now qualified FDA approval that allow patients to use them if prescribed by a doctor, but only Grail's Galleri test is commercially available. A handful of smaller insurers and self-insured companies cover the cost of Grail's test, but widespread use isn't expected until larger insurance companies and Medicare cover them, which won't come without broader FDA approval.

Motivated by the troubling number of cancer deaths for which no early detection now exists, Grail is investing significantly in refining and securing broader use of its technology, said Dr. Josh Ofman, president of Grail. The company has overseen and plans to continue conducting clinical studies in the United States, Canada and the United Kingdom to establish its test's accuracy and efficacy.

"There's a belief that everything's fine because we have these five single-cancer screening tests," Ofman said. "But nothing is fine. We're not winning the 'war on cancer.' We're losing 1,600 people a day. Our ability to detect asymptomatic, early-stage cancers — like ovarian, pancreatic and liver—is zero. Our goal at Grail is to completely transform the way we find cancer and to find it early before it's spread and is deadlier."

Since the Galleri test became commercially available in June 2021, more than 150,000 tests have been purchased, Ofman said.

Given that advancing age is the single biggest risk factor in developing cancer, bills now in the Senate and House would pave the way for Medicare to cover the tests once they receive broader FDA approval. Medicare coverage would improve access and affordability and decrease the significant racial and economic disparities in cancer screening and treatment, according to Rep. Terri Sewell, the first Black woman to serve in Alabama's Congressional delegation. Sewell is lead sponsor of the House bill, named for her mother, Nancy Gardner Sewell, who died of pancreatic cancer in 2021, at 81.

Seeking to bolster its test's credibility with Medicare recipients, Grail this year will initiate a study involving 100,000 Medicare patients designed to compare health outcomes of those who receive traditional cancer screenings with patients who undergo those screenings and an annual Galleri test. Medicare will cover the costs of the Galleri tests administered as part of the study.

Medicare coverage also could pressure more private insurers to cover the test, which would motivate more clinicians to learn about it. Royse experienced a two-month delay in learning about his pancreatic cancer after two doctors, including his primary care physician, refused to provide a prescription for the test because they either were unfamiliar with it or didn't think his cancer risk was high enough to justify it.

He ultimately obtained the prescription via a telehealth appointment with Grail, but even after his June 2022 test detected potential cancer markers, he couldn't schedule an appointment with his primary care physician for weeks, and another doctor dismissed additional testing as "too aggressive." Royse paid out of pocket for the MRI the day after receiving his test results that led to his cancer diagnosis.

A brutal six months of chemotherapy and surgery quickly followed, after which his surgeon gave him less than a 50% chance of surviving five years. Motivated largely to see his 18-year-old daughter graduate high school and beyond, Royse adopted an even healthier lifestyle, including vigorous exercise, no alcohol or processed sugar, cold therapy, saunas, nutritional supplements and meditation.

Since May 2023, he's also received emerging therapies developed in clinics in Japan and Holland and administered in San Francisco under a special FDA "compassionate use/expanded access" designation. His last chemotherapy was in February 2023, and he remains cancer-free.

"I feel like the world needs to know about early detection, especially as the average age of cancer patients drops," Royse said. "And secondly, I know it sounds trite, but the patient has to take control of their treatment, the patient has to be in charge. Your health is too important to entrust to a doctor."

Royse's difficulty in finding clinicians familiar with the test is one of many issues that must be addressed before they're made widely available, NCI's Minasian said. "What you don't want is a scenario with an assay [laboratory test] out there that you take to your doctor, and they don't know what to do with the results," she said.

Another consideration is how often the tests produce false positives (a result indicating a patient has cancer when they don't) or false negatives (a result showing a patient is cancer-free when they have the disease). Some experts warn that false positives could lead to a dramatic increase in unnecessary and sometimes invasive additional screenings, overwhelming the health care system and taxing an already financially strained Medicare. And patients receiving false-negative MCED results for cancers for which widely recommended screenings are now available could erroneously be lulled into foregoing those screenings, experts warn.

"It's also unknown how many people with negative tests go on to have a cancer diagnosis and how long there is between the test and the diagnosis," NCI's Minasian noted.

Grail's Ofman stressed that all cancer screenings produce false-positive results, many at far higher rates than his company's test. For example, the false-positive rate for breast cancer for a patient after 10 annual mammograms is 50%-to-60%, according to Susan G. Komen, while healthy patients who regularly receive colonoscopies starting at age 50 have experienced a false-positive rate for colon cancer of 18% by the age of 74.

Those who back the tests say the potential benefit of detecting deadly cancers early outweighs concerns about false-positive results. A 2021 study co-authored by four scientists either employed or funded by Grail estimates that adding its tests to today's recommended screenings could more than triple the total number of U.S. cancer cases detected by all screening methods — to about 612,000 annually — while false positives would climb about 9% — or about 740,000 incidences. "It's a very small penalty," Grail's Ofman said about the increase in false positive test results.

NCI's Minasian still urges caution. "Large-scale trials are expensive, and they take a lot of effort and a lot of time," she said. "That being said, we need those trials to answer these questions."