A blood-based screening test can accurately detect solid tumors and hematologic malignancies, even at early stages, according to study results published in Annals of Oncology.1

The multicancer early detection test, called Galleri™, was able to detect a wide range of cancers and establishes the beginnings of a new paradigm for cancer screening, according to study author Eric A. Klein, MD, chairman of the Glickman Urological & Kidney Institute at Cleveland Clinic in Ohio.

“Most cancer deaths in the United States and around the world are from cancers for which there is no screening test,” Dr Klein said. “A test like this would be useful in shifting the stage at which many cancers are diagnosed from late stage to earlier stages when they are easier to cure.”

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Dr Klein explained that the test uses cell-free DNA (cfDNA) sequencing and machine learning. It first provides a binary result: a cancer signal is detected or not detected. If a cancer signal is detected, the test then predicts where the cancer is located in the body.

GRAIL, Inc., the company that developed the test, has made it available in the United States by prescription only and to complement other, existing screening methods.2

Harnessing cfDNA

In the past, cfDNA has been harnessed to assess tumors that had already been identified, explained Michael J. Hall, MD, chair of the department of clinical genetics at Fox Chase Cancer Center in Philadelphia, Pennsylvania.

“We have used cfDNA to understand what genetic or genomic drivers are present in tumors without having to go in and cut the tumors out,” said Dr Hall, who was not involved in the study of the test. “It has also been used in certain types of cancers in a predictive fashion when we are concerned about monitoring risk for recurrence.”

The Galleri test harnesses cfDNA in a new and incredibly powerful way, Dr Hall added.

“Here, they are using it to try to screen or detect cancers that we wouldn’t otherwise know are there,” Dr Hall said. “Hopefully, it will allow us to detect them early enough to do something less invasive or morbid to the patient.”

Indeed, according to Dr Klein, the test would allow for a screening paradigm that is much different from existing cancer screening.

“We only have 5 established screening paradigms: PSA for prostate cancer, mammography for breast cancer, colonoscopy for colon cancer, Pap smears for cervical cancer, and low-dose CT for people at high risk for lung cancer,” Dr Klein said. “Currently, these tests are used to screen individuals for individual cancers. This would be a major shift to screen for multiple cancers at once.”

Study Results

Dr Klein and colleagues recently evaluated the test in a substudy of the Circulating Cell-free Genome Atlas (CCGA) study (ClinicalTrials.gov Identifier: NCT02889978).1

The researchers analyzed 4077 participants — 2823 with cancer and 1254 without cancer at 1 year of follow-up.

The test demonstrated high specificity for cancer signal detection and high accuracy for cancer origin prediction, and it detected more than 50 cancer types, the researchers found.

The specificity for cancer signal detection was 99.5%. The sensitivity was 51.5% overall but increased with increasing cancer stage — 16.8% for stage I, 40.4% for stage II, 77.0% for stage III, and 90.1% for stage IV.

Among patients with a true positive cancer detection result, the overall accuracy of cancer signal origin prediction was 88.7%.

The researchers also looked specifically at 12 cancers that account for approximately two-thirds of annual cancer deaths in the United States (anal, bladder, colorectal, esophageal, head and neck, liver/bile duct, lung, ovarian, pancreatic, stomach, lymphoma, and plasma cell neoplasms). 

The sensitivity of the test was 76.3% for the 12 cancers overall and 67.6% for stage I-III cancers.

“This test has the potential, if used as routine in patients at risk for those cancers, to find the cancers before symptoms occur and at an early enough stage when they should be curable,” Dr Klein said. “You can cure something like early-stage ovarian cancer, but you can’t cure late-stage ovarian cancer.”

Taking Action

Dr Hall suggested a test like Galleri could have incredible value. As a blood test, this is something that could be performed at any doctor’s office, compared with existing screening methods that are more expensive and often require patients to go to specific locations.

Dr Hall also pointed out that the test has a low failure rate (0.8%) and a low false-positive rate (0.5%).

“This study tells us that the technology is pretty powerful at ruling out cancer,” Dr Hall said. “If you don’t actually have cancer, the likelihood that the test would tell you that you do have cancer is very small, which is very reassuring.”

Dr Klein said the goal would be to use this test in the general population of people who are at risk for cancer.

“The average person is not at risk until they reach age 50 if you look at cancer incidence across all cancers,” Dr Klein said. “Maybe this test could be recommended at regular intervals.”

Another potential population for this type of test is people who have inherited a syndrome that puts them at higher risk for developing cancers, such as BRCA mutation carriers or families with Lynch syndrome.

“We are not there yet,” Dr Klein said, “but this current study opens the door to this possibility.”

More to Learn

Dr Klein said the CCGA studies were the first set of studies to test this multicancer early-detection technology. The next series of studies will assess its utility in some of the intended-use populations.

For example, the PATHFINDER study (ClinicalTrials.gov Identifier: NCT04241796) was designed to assess the implementation and performance of the screening test in individuals aged 50 years or older.

Interim results from PATHFINDER showed that the test accurately detected 29 cancers across 13 types.3,4 The positive predictive value was 44.6%. When cancer was confirmed, the accuracy of the test for detecting the cancer signal origin was 96.3%.

“We also have to look more closely at the false-negative rate and false-positive rate, and what harm comes to patients from having a positive test and being subjected to further diagnostic evaluation,” Dr Klein said.

Specifically, research is needed to evaluate patients with a positive screening test in whom no cancer is found by standard diagnostic modalities.

“What does that mean? Is the test so sensitive that it picked up a tumor that standard blood and imaging tests can’t even see yet, or is it a true false positive?” Dr Klein asked. “It will take some time to sort that out.”

Despite that, Dr Klein and Dr Hall were excited about the potential of this screening test.

“One of the things we are nervous about in the cancer community is we are seeing the age of cancers shifting lower and lower,” Dr Hall said. “We have questioned if we then need to shift screening ages down. Maybe we could use a test like this to noninvasively screen that younger population and, if something is found, send just those people for more targeted screening.”

Dr Hall agreed that more studies are needed, especially studies to test whether this additional screening leads to lives saved.

Disclosures: This research was supported by GRAIL, Inc. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


  1. Klein EA, Richards D, Cohn A, et al. Clinical validation of a targeted methylation-based multi-cancer early detection test using an independent validation set. Ann Oncol. Published online June 23, 2021. doi:10.1016/j.annonc.2021.05.806
  2. Blood test for early detection of cancer: Final study results support screening use. News release. European Society for Medical Oncology (ESMO). June 25, 2021. Accessed July 27, 2021.
  3. GRAIL presents interventional PATHFINDER study data at 2021 ASCO Annual Meeting and introduces Galleri, a groundbreaking multi-cancer early detection blood test. News release. GRAIL, Inc. June 4, 2021. Accessed July 27, 2021.
  4. Beer TM, McDonnell CH, Nadauld L, et al. Interim results of PATHFINDER, a clinical use study using a methylation-based multi-cancer early detection test. J Clin Oncol. 2021;39:(suppl 15; abstr 3010). doi:10.1200/JCO.2021.39.15_suppl.3010

This article originally appeared on Cancer Therapy Advisor