
A blood-based multicancer early detection (MCED) test that predicts cancer signal origin (CSO) has a positive predictive value of 60.3 percent for participants aged 50 years or older without clinical suspicion of cancer, with specificity of 99.64 percent, according to a study published online Sept. 22 in Nature Medicine.
Nima Nabavizadeh, M.D., from the Oregon Health & Science University in Portland, and colleagues expanded clinical evidence for the MCED test in the prospective interventional PATHFINDER 2 study, which examined coprimary end points of MCED performance metrics and safety in participants aged 50 years or older without clinical suspicion of cancer. A total of 35,878 participants were enrolled between December 2021 and July 2024.
The researchers found that the cancer detection rate was 0.54 percent among 32,007 performance-analyzable participants, while the positive predictive value and negative predictive value were 60.3 and 99.2 percent, respectively; specificity was 99.64 percent. Episode sensitivity was 39.3 and 69.8 percent for all cancers and in the prespecified 12-cancer subgroup, respectively. The positive likelihood ratio was 108.9 and negative likelihood ratio was 0.61; to detect one cancer, the number needed to screen was 185. The prediction accuracy was 91.3 percent for CSO. Overall, 0.6 percent of 35,335 safety-analyzable participants had invasive procedures after a positive MCED test, 90.5 percent of which were nonsurgical.
“We screen for just five cancers, yet the ones we can’t screen for cause up to 70 percent of cancer deaths in this country; that’s the gap this blood test helps close,” Nabavizadeh said in a statement.
Several authors disclosed ties to pharmaceutical and biotechnology companies, including GRAIL, which is developing this MCED test and funded the study.
An MCED test, also known as a multi-cancer detection (MCD) test, is a blood-based liquid biopsy that analyzes cell-free DNA or other biomarkers to screen for dozens of different cancer types from a single sample. Some MCD tests suggest where the cancer started, while others may only show that cancer could be present without identifying a probable type or location.
MCED tests differ from conventional cancer screenings because they use a single blood draw to screen for multiple cancers simultaneously, whereas conventional screenings target only one specific cancer type at a time.
While MCEDs can detect cancer signals, they cannot diagnose cancer. If a clinician identifies biomarkers that may indicate cancer, they will refer the patient to further diagnostic testing to confirm whether a tumor is actually present.
In the PATHFINDER 2 study, researchers used MCED to predict the potential origin of a cancer signal to guide follow-up.
The MCED test could potentially identify signals from cancers that don’t currently have routine guideline-recommended screening. A positive result from the screening tool still requires a diagnostic workup to confirm the presence of cancer. With this in mind, clinicians may need to coordinate imaging, specialty referrals, biopsies, and other follow-up testing. False positives, false negatives, overdiagnosis, and downstream procedures remain important considerations when using MCED tests. The study’s authors note that randomized trials and longer follow-up are still needed to determine clinical utility.
Black patients experience disparities in incidence, mortality, and stage at diagnosis for several cancers, making earlier detection an important area of research. At the same time, a new screening technology can only help reduce disparities if the populations most affected by cancer are adequately represented in its development and validation.
Clinicians should consider whether evidence for MCED testing adequately reflects the racial and demographic diversity of the patients they serve.

While the study’s findings are promising, questions still remain:
For clinicians, conventional cancer screenings will still remain the standard in diagnosing cancer. MCED tests can be a valuable tool for identifying potential biomarkers that may signal cancer, but cannot officially diagnose cancer.
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