A multi-cancer early-detection (MCED) blood test can detect cancers in patients presumed to be healthy, according to results from the PATHFINDER study.1
The test was able to detect solid tumors and hematologic malignancies, early-stage and recurrent cancers, and cancers for which there are no standard screening procedures. However, the test also produced false-positive and false-negative results.
These findings from the PATHFINDER study were presented at ESMO Congress 2022 by Deborah Schrag, MD, of Memorial Sloan Kettering Cancer Center in New York, New York.
Prior to PATHFINDER, the MCED test had been successful in case-control trials but had not been tested prospectively in a screening trial of presumably healthy individuals.2
About PATHFINDER and the MCED Test
The PATHFINDER study (ClinicalTrials.gov Identifier: NCT04241796) enrolled 6621 adults who were at least 50 years of age and had no clinical evidence of cancer.1 Participants were divided into 2 cohorts depending on whether they had additional risk factors for cancer, such as a lifetime history of smoking at least 100 cigarettes, hereditary cancer predisposition, or a history of cancer with treatment completed at least 3 years prior.
Dr Schrag presented results for patients who were enrolled from December 2019 to December 2020 at 7 US sites and were followed for 1 year from the date on which MCED testing was performed.
Dr Schrag explained that MCED testing involved a targeted methylation, next-generation-sequencing-based assay to detect and analyze cell-free DNA as well as machine-learning technology to detect a “cancer signal” and predict the likely sites of origin for that signal.
The MCED test results were reported on day 15. If a cancer signal was detected, a diagnostic investigation for cancer was performed. Participants without a cancer signal were asked to continue US Preventive Services Task Force (USPSTF)-approved screening tests for cancer (eg, mammography and colonoscopy) at guideline-concordant intervals.
The primary outcome was the extent of diagnostic testing required for resolution when a cancer signal was detected by the MCED test. The nature of the diagnostic evaluation was at the discretion of the treating physician. The researchers also assessed cancer status at 1 year for all participants.
Initial Cancer Detection and 1-Year Follow-Up
There were 3681 patients in the cohort with cancer risk factors and 2940 patients without risk factors. At baseline, most patients in both cohorts were up to date with USPSTF-recommended colorectal cancer screening (91% with risk factors and 92% without risk factors) and breast cancer screening (78% and 83%, respectively). The average age was similar between the 2 cohorts (64.7 years and 61.6 years, respectively), and most patients were White (93% and 89%, respectively).
The MCED test detected a cancer signal in 1.4% (92/6621) of patients with analyzable samples. There was little difference between the cohort with risk factors (1.5%) and the cohort without them (1.2%).
Cancer was confirmed in 35 patients with a cancer signal on the MCED test, but 2 patients were excluded from the diagnostic workup analysis because diagnostic testing was started before the MCED test results were returned. An additional 57 patients had a false-positive MCED test result.
The median time to diagnostic resolution was 79 days overall — 57 days for patients with a true-positive result and 162 days for those with a false-positive result. Seventy-three percent of patients with a true-positive result and 42% of those with a false-positive result had diagnostic resolution in less than 3 months.
Among the 35 patients with a true-positive signal, 36 cancers were diagnosed — 24 in the high-risk cohort and 11 in the cohort without risk factors. In 34 of the true-positive results, the MCED test correctly predicted the origin of the malignancy.
Eighteen of the 35 cancers were solid tumors, and 17 were hematologic malignancies. Patients had cancers of the breast (n=5), colon/rectum (n=2), prostate (n=2), liver (n=1), intrahepatic bile duct (n=1), lung (n=1), pancreas (n=1), small intestine (n=1), uterus (n=1), ovary (n=1), and bone (n=1). They also had lymphoma (n=12), lymphoid leukemia (n=2), Waldenstrom macroglobulinemia (n=2), and myeloma/plasma cell disorders (n=1).
Twenty-six of the cancers diagnosed by MCED testing lacked standard screening procedures, 14 were early-stage cancers, and 7 were recurrent cancers.
For both the true-positive and false-positive test results, more than 90% of the diagnostic studies were imaging procedures. Invasive procedures were performed in 82% of patients with true-positive results and 30% of those with false-positive results.
No serious adverse events were reported from MCED testing or from confirmatory diagnostic procedures.