The multi-cancer early detection (MCED) test is a blood-based targeted methylation assay designed to identify cancer signals from cell-free deoxyribonucleic acid (cfDNA) and predict their likely cancer signal origin (CSO) to guide diagnostic evaluation.¹ At the ESMO Congress 2025, Dr. Nima Nabavizadeh from the Cancer Early Detection Advanced Research Center, Knight Cancer Institute, Oregon Health & Science University in the United States (US), presented the initial results from the registrational PATHFINDER 2 study.¹ The findings found that the MCED test accurately detected cancer signals across a diverse intended use population, showing strong performance and a favorable safety profile.¹

The MCED test has been clinically validated in multiple trials, including CCGA, PATHFINDER, REFLECTION, and NHS-GALLERI, involving ≥380,000 participants globally.¹ PATHFINDER 2 is the largest interventional study conducted in the US to date that evaluates the safety and performance of the MCED test.¹ This prospective study enrolled 35,878 participants aged ≥50 years from 32 North American healthcare systems.¹ Eligible individuals were not undergoing or referred for diagnostic evaluation for cancer, and had no personal history of invasive solid tumor or hematologic malignancy and/or cancer treatment within the three years prior to enrollment.¹

All participants underwent blood collection and MCED testing, with results communicated to both participants and clinicians.¹ Follow-up was guided by the predicted CSO and continued until diagnostic resolution for all participants.¹ For positive MCED results in participants with no cancer detected, protocol-specified diagnostic positron emission tomography-computed tomography (PET-CT) was performed prior to diagnostic resolution.¹ All participants were actively followed for three years to assess their cancer status and the utilization of cancer screening tests, with relevant clinical information collected annually.¹ The safety-analyzable cohort included 25,114 participants who underwent diagnostic evaluation after receiving their MCED results.¹ Of these, 23,161 participants completed the 12-month cancer status assessment, which was used to evaluate performance metrics.¹ The median age was 65 years (interquartile range [IQ] 59-71), with 43.2% men, and the cohort was racially diverse.¹

Among 23,161 participants evaluated for performance, the MCED test detected 216 positive results, of which 133 were true positives, yielding a positive predictive value (PPV) of 61.6% (95% CI: 54.9-67.8).¹ Of the 22,945 participants with a negative MCED result, 22,749 were confirmed to have no cancer, corresponding to a negative predictive value (NPV) of 99.1% (95% CI: 99.0-99.3%).¹ The observed PPV was higher than that reported in prior clinical studies and real-world experience, which generally ranges from 42.9%-49.4%.¹ Notably, the PPV was substantially higher than those reported for established single-cancer screening tests.¹ Episode sensitivity was 40.4% (95% CI: 35.3-45.8) with specificity reaching 99.6% (95% CI: 99.5-99.7), demonstrating robust detection accuracy across the population over the 12 months of follow-up.¹

Of the 329 cancers detected within the 12 months of MCED testing, 133 (61%) were MCED-detected.¹ Importantly, MCED testing increased the number of screen-detected cancers by more than sevenfold when added to standard US Preventive Services Task Force (USPSTF)-recommended screenings (breast, cervical, colorectal, and lung), and approximately threefold when prostate cancer was included.¹ Among these, 73% involved cancer types without any existing screening recommendations, highlighting the test’s ability to uncover otherwise undetectable malignancies.¹

Most MCED-detected new cancers were identified at early stages, with 53.5% diagnosed at stage I-II and 69.3% at stage I-III.¹ Early-stage detection is especially important for cancers that do not have standard screening methods, as 74% of stage I-II cases fall into this category.¹ The most common types in this group include head and neck, liver, colorectal, lymphoid, and pancreatic cancers.¹ The accuracy of the first CSO prediction for true positive cases was 91.7% (95% CI: 85.8-95.3), supporting the clinical utility of CSO guidance in streamlining follow-up investigations.¹ Accurate CSO predictions guided efficient diagnosis following a positive MCED result, with a median time to diagnostic resolution of 36 days (IQ range: 24-61) for true positives.¹

The MCED test demonstrated an excellent safety profile when implemented in the intended use population.¹ No serious study-related adverse events were reported during the diagnostic work-ups.¹ Only 0.6% of participants underwent invasive procedures to evaluate a positive MCED result, which were approximately twice as common among true positives when compared with false positives, demonstrating targeted diagnostic efficiency by directing interventions to those with cancer while avoiding unnecessary procedures in those without.¹

Collectively, these findings from the largest interventional MCED study conducted in the US to date confirm that the MCED test demonstrates robust performance and increased cancer detection across a broad population, while enabling prompt and efficient diagnostic resolution with a favorable safety profile, further supports the potential utility of MCED in early multi-cancer detection.¹