The Competitive Landscape

In the two years since GRAIL's Galleri became commercially available in the US, a second MCED test was launched commercially at a lower price point (Exact Sciences’ Cancerguard), a third company obtained FDA Breakthrough Device Designation for its own MCED test (Guardant’s Shield MCD), Medicare coverage legislation was signed into law, the National Cancer Institute began enrolling patients in the first federally sponsored evaluation of MCED tests (Vanguard), and the largest randomized controlled trial (RCT) ever conducted for any MCED test has reported topline results (NHS-Galleri).

This post maps the competitive field as it stands in 2026, covering both the strategic picture and head-to-head performance data for every MCED test whose results have been published or presented at a major conference. Note that the comparisons should be taken with a massive grain of salt because the MCED tests I'll be discussing were studied in different trials with different study designs and study populations. If you want to understand the differences between how each test works, I advise you to read the post, “How MCED Testing Works”, if you haven't already.

Performance Data

Here are the headline numbers for all three tests, followed by some important context.

MCED Test Comparison

*Cancerguard development and validation cohort data exclude breast and prostate cancers. Including all cancers, overall sensitivity in the development cohort was 57.8%. Source: Cancerguard Clinician Brochure. These are case-control cohorts, not prospective screening data.

PATHFINDER 2 and NHS-Galleri figures reflect data presented at ASCO 2026.

At first glance, Cancerguard appears to have the highest sensitivity. However, the 64.1% sensitivity number comes from a development cohort of 590 cancer patients and 2,434 non-cancer controls, as reported in the Cancerguard Clinician Brochure rather than a published manuscript or conference abstract. The 51.5% sensitivity for Galleri in Circulating Cell-free Genome Atlas (CCGA) comes from a case-control validation cohort, comparable in design (though not in specificity threshold) to the Shield MCD and Cancerguard data. The 39.3% sensitivity for Galleri from PATHFINDER 2 (the registrational result presented at ASCO in 2026; the earlier ESMO 2025 interim analysis had reported 40.4% sensitivity) comes from a prospective interventional study of 32,007 real screening patients (asymptomatic adults who did not know whether they had cancer), which is a harder and more realistic test of the technology. The drop in sensitivity is expected between a case-control study and a prospective screening study. Shield MCD and Cancerguard do not have data from a prospective screening study, and it's presumed, if the same pattern holds, that their sensitivities in a true screening population will be lower than the numbers currently cited.

GRAIL

Galleri's performance data come from the most rigorous evidence hierarchy in the space. PATHFINDER 2, with 32,007 analyzable screening patients in its registrational analysis reported at ASCO 2026, produced what I consider the most clinically relevant numbers: a 39.3% overall sensitivity and 99.6% specificity in an intended-use population. As stated above, the lower sensitivity in PATHFINDER 2 is expected, since prospective screening populations are not enriched for patients with known cancer diagnoses like case-control studies are. On top of this, GRAIL has real-world commercial data from over 500,000 tests and the NHS-Galleri randomized controlled trial of 142,924 participants, which is the only randomized controlled trial of any MCED test to report results. No other company has accumulated a foundation of evidence this deep.

Commercial position: GRAIL sold more than 185,000 Galleri tests in 2025, growing US revenue 26% year-over-year to $136.8 million. GRAIL went public via the Illumina spinoff in June 2024, trades on Nasdaq, and raised more than $435 million in late 2025 as it continues to invest in commercial growth and the regulatory process. The company also expanded access to Galleri via digital health platforms, including Hims & Hers, Function Health, and Everlywell, and announced a sales force expansion following the NHS-Galleri and PATHFINDER 2 results.

Regulatory position: Galleri received Breakthrough Device Designation in 2018, and GRAIL completed its modular PMA submission to the FDA on January 29, 2026, which was the first PMA submission for any MCED test. The filing includes data from PATHFINDER 2 and the prevalent screening round of the NHS-Galleri trial, supported by a bridging analysis comparing the study version of Galleri to the refined version. Given the Breakthrough pathway's priority review provisions, a decision could come as early as mid-to-late 2027, though the FDA has never approved an MCED test, and there is no precedent for timeline expectations. GRAIL has also partnered with Samsung to bring Galleri to South Korea, signaling international expansion.

A note on NHS Galleri: GRAIL first released topline results from the NHS-Galleri trial in a press release in February 2026, and the primary results were presented at ASCO in June 2026. As previously mentioned, this was the first and largest prospective RCT of any MCED test, conducted in partnership with England's NHS over three years in 142,924 participants aged 50 to 79. The results are mixed. The primary endpoint, a statistically significant reduction in combined stage III and IV cancer diagnoses, was not met. However, the secondary and exploratory findings tell a more nuanced story. Adding Galleri to standard-of-care cancer screening produced, in my opinion, a clinically meaningful reduction in Stage IV diagnoses across the pre-specified 12 cancer types (a statistically significant 14% reduction, with an incidence rate ratio of 0.86). Stage IV diagnoses decreased with each year of sequential screening, with a greater than 20% reduction observed in the second and third screening rounds. A four-fold improvement in overall cancer detection rate was observed compared to standard screening alone for breast, colorectal, cervical, and high-risk lung cancers. There was an increase in Stage I and II diagnoses among the 12 deadly cancer types in the intervention arm, and screening with Galleri resulted in a reduction in cancers detected through emergency clinical presentation. Notably, there was a (reportedly) higher-than-anticipated incidence of stage III cancers in the trial. This may be the key to understanding why the combined stage III-IV endpoint was missed while stage IV reduction was substantial. If Galleri screening pulled cancers that would have presented as stage IV into stage III (detecting them before distant metastatic spread but after advancement to locoregional disease), that is exactly the kind of stage migration you would hope a screening test produces. However, this mathematically undermines a combined Stage III-IV reduction endpoint, because the Stage III denominator is growing even as Stage IV is shrinking. GRAIL announced plans to extend the trial's follow-up period by 6-12 months, suggesting the company believes that a longer follow-up will strengthen the stage shift effect. The NHS-Galleri results do not provide mortality data, and thus, the question of whether finding cancer earlier with this test makes people live longer remains unanswered by this trial.

Exact Sciences

The foundational DETECT-A study of approximately 10,000 women aged 65 to 75 evaluated an earlier version of the company's MCED test (CancerSEEK) rather than the currently commercially available Cancerguard test. ASCEND-2 evaluated a newer multi-analyte test in a prospectively collected cohort of over 6,000 samples (approximately a quarter of which were from people with cancer). The Falcon Registry is enrolling participants under an FDA-reviewed Investigational Device Exemption and may eventually provide data supporting the utility of Cancerguard.

Commercial position: Cancerguard is (as of the time of this book) priced at $689 and is available through Quest Diagnostics with direct-to-consumer telehealth access. Exact Sciences reported over $3.25 billion in total company revenue for 2025, though most of this is not driven by Cancerguard. On November 20, 2025, Abbott, an approximately $200 billion global healthcare company with an existing diagnostics business generating more than $9 billion annually, announced an agreement to acquire Exact Sciences.

Regulatory position: No PMA submission has been filed by Exact Sciences for Cancerguard to date, and there is no publicly defined submission timeline. Under Abbott's ownership, the regulatory strategy could change, as Abbott may pursue using Exact Sciences' existing data, wait until the Falcon Registry study is further along, or invest in additional studies.

Guardant Health

Guardant Health is the only competitor that has already successfully navigated the FDA PMA process, having done so with their Shield blood test for colorectal cancer. Shield MCD, the multi-cancer extension covering 10 tumor types, received FDA Breakthrough Device Designation and was selected for the National Cancer Institute Vanguard Study. Much of Shield MCD's data comes from two previously described conference presentations in 2025, at AACR and the American Society for Clinical Oncology (ASCO), based on a case-control study.

Commercial position: As of the time of this book, Shield MCD is not yet commercially launched (for individual purchase) as a standalone MCED product. Healthcare providers can order the test, which generates real-world ordering experience without a formal commercial launch. Guardant's overall revenue exceeded $700 million in 2025 across its oncology portfolio.

Regulatory position: Shield MCD received Breakthrough Device Designation in 2025. No PMA submission timeline has been announced, but Guardant's institutional knowledge from the Shield colorectal cancer screening test approval could be advantageous. Selection for the National Cancer Institute Vanguard Study (one could argue) provides independent, government-funded validation and could be used as part of a PMA application.

Differences in Specificity Thresholds

Practical differences emerge at different pre-specified specificity thresholds. These thresholds are moving targets and could be different in the commercial products being delivered, but I'll stick to the published data for now. In a hypothetical screening population of 10,000 people with approximately 1% cancer prevalence, at Galleri's 99.5% specificity, approximately 50 cancer-free people receive a false positive. At Shield MCD's 98.5% specificity, that number rises to approximately 140. At Cancerguard's 97.4%, it is approximately 260.

Whether the hoped-for gains in sensitivity from Cancerguard or Shield MCD justify the specificity costs depends on stage-specific data. If additional detections are mostly early-stage cancers that would otherwise be missed, the tradeoff may be worth it. But if they are mostly late-stage cancers that would have been caught eventually, more false positives may be generated for marginal benefit.

What I Think

Again, these tests are not at the same stage of clinical validation, so comparisons should be made extremely cautiously.

Galleri has been evaluated in large prospective screening trials whose results have been published in multiple peer-reviewed publications, accumulated real-world evidence from hundreds of thousands of tests, and has a PMA submission to the FDA. The NHS-Galleri study did not achieve its primary endpoint of a reduction in combined stage III-IV cancers, although, as previously stated, there may be some underlying issue with the trial design that could help explain this.

Cancerguard has a compelling scientific rationale in its multi-biomarker approach and interesting performance data, but the commercial test has not been validated in a prospective interventional study of intended-use screening individuals. The higher sensitivity figure currently rests on test-development data rather than the kind of prospective evidence that would be required for FDA approval or guideline endorsement.

Shield MCD's early data are encouraging. The sensitivity and cancer signal origin accuracy seem competitive, and Guardant's institutional FDA experience is a competitive advantage. However, the evidence is at a much earlier stage with case-control data from fewer than 1,000 participants, no stage-specific sensitivity, no prospective screening results, and no peer-reviewed publication.