In a prospective cohort study (PATHFINDER) reported in The Lancet, Deb Schrag, MD, MPH, FASCO, and colleagues evaluated the performance of blood-based testing for multicancer early detection in adults without signs or symptoms of cancer.
As stated by the investigators, “Multicancer early detection blood tests can detect a cancer signal from circulating cell-free DNA (cfDNA). PATHFINDER was a prospective cohort study investigating the feasibility of multicancer early detection testing for cancer screening.”
Study Details
In the study—performed in oncology and primary care outpatient clinics at seven U.S. health networks—a convenience sample of individuals aged ≥ 50 years without signs or symptoms of cancer consented to multicancer early detection testing between December 2019 and December 2020. After blood collection, cfDNA was analyzed and results were returned to participants’ doctors. If a methylation signature suggestive of cancer was detected, predicted cancer signal origin(s) were used to guide diagnostic assessment. The primary outcome measures were time to and extent of diagnostic testing required to confirm the presence or absence of cancer.
Deb Schrag, MD, MPH, FASCO
Key Findings
Among 6,661 evaluable participants, 63.5% were women, 36.5% were men, and 91.7% were White.
A cancer signal was detected in 92 participants (1.4%); of the 92, 35 (38.0%) were diagnosed with cancer (true-positives) and 57 (62.0%) had no cancer diagnosis (false-positives).
Among 6,529 participants with no cancer signal detected, 95.5% were true-negatives, 1.3% were false-negatives, and 3.2% did not have a cancer status assessment available by the end of the study.
In an analysis excluding two participants with diagnostic assessment beginning prior to reporting of multicancer early detection test results, median time to diagnostic resolution among participants with a cancer signal was 79 days (interquartile range [IQR] = 37–219 days), including 57 days (IQR = 33–143 days) in true-positive cases and 162 days (IQR = 44–248 days) in false-positive cases. Laboratory tests were performed in 26 (78.8%) of 33 true-positive cases and 50 (87.7%) of 57 false-positive cases; imaging was performed in 30 (90.1%) true-positive cases and 53 (93.0%) false-positive cases. Nonsurgical (eg, endoscopy, bone marrow biopsy, core biopsy, fine needle aspiration, and pap smear) or surgical procedures were performed in 27 (81.8%) true-positive cases and 17 (29.8%) false-positive cases; surgery was performed in 3 true-positive cases and 1 false-positive case.
The investigators concluded, “This study supports the feasibility of multicancer early detection screening for cancer and underscores the need for further research investigating the test’s clinical utility.”
Dr. Schrag, of Memorial Sloan Kettering Cancer Center, is the corresponding author for The Lancet article.
Disclosure: The study was funded by GRAIL. For full disclosures of the study authors, visit thelancet.com.
