More false than true positive

Dr. Deborah Schrag

PARIS – New results from a large future trial are giving a better idea of ​​how a blood test that can detect many cancers performs in a “real-life” environment.

“As this technology develops, people should continue to have standard cancer screening, but this is a glimpse of what the future may hold,” said study researcher Deborah Schrag, MD, MPH, chief of medicine, Memorial Sloan Kettering Cancer Center, New York City.

For the PATHFINDER study, the Galleri blood test (developed by Grail) was used in 6,621 healthy individuals over 50 years of age, with or without cancer risk factors (eg smoking history or genetic risk).

A positive cancer signal was found in 92 individuals (1.4%).

None of the individuals who tested positive for cancer at the time of testing were known. Subsequent examinations, which can include scanning and/or biopsy, found cancer in 38% of those who tested positive.

“When the test was positive, the tests were usually done in less than 3 months,” Schrag commented, adding that “the blood test usually predicts the origin of the cancer.”

File Schrag File the findings Here at the 2022 ESMO Annual Meeting.

Approaching comment, Anthony J. Olzansky, MD, RPh, vice president of research at Fox Chase Cancer Center, Philadelphia, PA, noted that using a blood test to “spot” cancer has long been on patients’ minds. “It’s not uncommon to hear oncologists ask, ‘Why didn’t my doctor detect cancer early, in blood tests?'”

As this study suggests, finding a malignancy before it becomes apparent on imaging or due to symptoms is one step closer to becoming a reality. “Although this is an important study, it should be noted that only about 40% of patients who tested positive were found to have cancer,” Olzansky said. “Conversely, about 60% of patients who test positive are likely to have experienced a significant amount of anxiety that may persist even after further testing has not revealed metastasis.”

Another important issue is that such testing can result in significant health care costs. “Less than out of every 100 participants tested positive, and these patients underwent further tests to interrogate the result,” he added. It also remains unclear whether early detection of cancer will lead to better outcomes.

Whether or not the test will be cost-effective remains unknown, as Schrag confirmed that they do not have a formal cost analysis at this time. “This technology is not ready for population-wide screening, but as technology improves, costs will come down,” she said.

Schrag also added that this is a new concept and that experience shows that it is possible to detect cancer using a blood test. “It was not designed to determine whether the test can reduce cancer mortality, which is clearly the purpose of screening, but it is premature,” she said.

Results details

Gallery test uses cell-free DNA (cfDNA) and machine learning to detect a common cancer signal across more than 50 types of cancer as well as to predict the origin of a cancer signal (CSO).

Overall, the test revealed a cancerous signal in 1.4% (n = 92) of participants with analysable specimens.

A total of 90 participants underwent diagnostic tests (33 true positives and 57 false positives). Among true positives, 81.8% underwent more than one invasive diagnostic test, as did 29.8% of false positives.

The specificity was 99.1%, the positive predictive value (PPV) was about 40%, and 73% of those who were true positive had a diagnostic accuracy in <3 months.

Of the diagnosed cancers, 19 were solid tumors and 17 were hematomas. Seven were diagnosed in someone with a history of cancer, 26 were diagnosed without standard screening, and 14 were diagnosed at an early stage.

“What’s exciting about this new model is that many of these were cancers for which we don’t have standard screening,” Schrag said.

Schrag noted that due to the great interest in this study, the manufacturer is working to improve the test and improve the test. Re-analysis was performed on all samples using a polished version of the test.

“Importantly, the new analysis identified fewer patients with positive signals, from 1.4% to 0.9%,” she said. “Quality improved to 99.5% as did PPV – from 38% to 43.1% – and more people need to be screened for cancer – up to 263 from 189.”

False positives

PREVIOUS, VERY SIMILAR RESULTS FROM THE PATHFINDER EXPERIENCE has been shown Last year at the annual meeting of the American Society of Clinical Oncology and was reported by Medscape Medical News in time.

Max Dehn, MD, PhD, associate professor of radiation oncology at Stanford University, California, was one of the invited speakers for the study.

He noted that there are more false positives than true positives, and noted that “there have been a large number of invasive procedures in false positives, which can harm these non-cancer patients.”

Dehn also explained that most of the true positives were for lymphoid malignancies, not solid tumors, and it is not known whether early detection of lymphatic malignancy is of clinical benefit.

The Galleri test is already available in the United States and is offered by a number of US health networks. However, it is not approved by the US Food and Drug Administration and is not covered by medical insurance, so individuals have to pay about $950 for it out of their pocket.

Although some experts are excited about its potential, calling it a “game-changer,” others worry that there are no clinical pathways in place yet to deal with the results of this blood test, and say it’s not ready for prime time, as Previously mentioned by Medscape Medical News.

The study was funded by Grail, an Illumina subsidiary. Schrag has reported on his relationships with Grail, the Journal of the American Medical Association, and Pfizer. Several co-authors also disclosed relationships with the industry. Olszanski reported participating on the advisory boards of BMS, Merck, and Instil Bio, and running trials for them.

ESMO 2022. Abstract 9030. It was introduced on September 11, 2022.

Roxanne Nelson is an award-winning registered nurse and medical writer who has written for many major news outlets and is a regular contributor to Medscape.

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