In recent years, genomic-based blood testing has been heralded as a promising tool for early detection in a wide range of cancers. At the American Association for Cancer Research Virtual Annual Meeting I, two research teams independently developing such blood tests reported compelling data on the specificity and sensitivity of their tests.

Earlier detection is widely considered key to stemming cancer, yet routine screening is available for only a handful of cancers. In recent years, however, genomics-based blood testing has been heralded as a tool with the potential to spot a range of malignancies at an early stage. At the American Association for Cancer Research (AACR) Virtual Annual Meeting I: April 27–28, 2020, two teams independently developing such blood tests offered compelling data on the specificity and sensitivity of their products.

“The dream of early detection is to identify cancer as early as possible while there is still a good chance for successful treatment,” said Nickolas Papadopoulos, PhD, of Johns Hopkins School of Medicine in Baltimore, MD. To this end, Papadopoulos and his team developed DETECT-A, a liquid biopsy that combines genomic screening of circulating tumor DNA for 16 common cancer mutations with an analysis of nine protein biomarkers.

The researchers assessed DETECT-A in a prospective, interventional study of 9,911 women ages 65 to 75 with no history of cancer. Liquid biopsy results indicated that 127 of the women might have cancer, so they had PET-CT scans. The scans showed possible cancer in 64 women, 26 of whom were subsequently diagnosed with a malignancy in any of 10 tissues. Seventeen women were diagnosed with local or regional disease. Eleven patients are in remission, and nine are undergoing treatment or have stable disease. The false-positive rate was less than 1%.

The results, published concurrently with the presentation, show that “it is feasible for a minimally invasive blood test to safely detect several types of cancers in individuals without known cancer,” Papadopoulos said. He is now developing a more advanced test called CancerSEEK (Thrive Earlier Detection), which employs machine learning to increase sensitivity and specificity.

A blood test being developed by Grail takes a different approach: It involves targeted sequencing of more than 100,000 methylation regions in circulating cell-free DNA likely to indicate cancer. Recently, Grail reported that in a validation set of 654 people with cancer and 610 healthy participants, the test had an overall detection rate of 43.9% for stage I to III cancers, which rose to 67.3% for 12 cancers responsible for roughly 63% of U.S. cancer deaths. The test had a false-positive rate of less than 1%, and it correctly identified the tissue of origin in 93% of cases.

At the AACR meeting, David Thiel, MD, of the Mayo Clinic in Rochester, MN, announced that the test performed similarly on a subset of healthy participants with a high clinical suspicion of cancer but no diagnosis, detecting 46.7% of cancers ahead of a confirmed diagnosis—with no false positives—and identifying the cancer's origin in 97.1% of those cases. “These findings suggest the … test could potentially be utilized to accelerate cancer diagnosis by directing diagnostic workup to predicted tissue of origin among individuals with high suspicion of cancer,” Thiel said. The prospective STRIVE and SUMMIT studies are further validating the test.

David Huntsman, MD, of the University of British Columbia in Canada, the studies' discussant, considers cancer screening the area in which genomics-based blood testing could have the biggest impact. Yet, screening is also the most challenging. “The assays need to have exquisite sensitivity to detect small tumors; the specificity needs to be close to perfect,” Huntsman said. “Both studies showed tremendous progress” in boosting specificity, he added, and are moving in the right direction on improving sensitivity—a key factor for cost effectiveness.

When thinking about deploying such tests on a large scale, the goal of both groups, cost effectiveness becomes even more important. “We will need to show improved survival measured by prospective studies,” he said, before such tests can be adopted in the clinic. –Catherine Caruso