Multicancer Early Detection Testing: a Population-Based Screening Strategy?

Early detection remains the most effective strategy for improving cancer outcomes, yet screening options remain limited. The US Preventive Services Task Force recommends screening for breast, colorectal, cervical, and lung cancers in select populations.¹ However, approximately 87.2% of cancer deaths occur in cancers with no guideline-recommended screening tests. Even when tests do exist, patients face multiple barriers, including limited awareness, personal hesitation, competing health priorities, and socioeconomic challenges, and primary care providers face the practical impossibility of helping their patients navigate these barriers to improve screening adherence. These realities have motivated the search for streamlined, accessible strategies to address existing gaps in cancer screening.

Multicancer early detection (MCED) testing has emerged as an exciting strategy to expand cancer screening. MCED technologies rely on advances in liquid biopsy and biomarker discovery to detect multiple cancer types simultaneously from a single blood draw. By consolidating detection into one test, MCED approaches may reduce the number of tests needed to screen for cancer in individual patients and facilitate earlier diagnoses across a broader spectrum of cancers, including those without existing screening modalities.

For clinical adoption, MCED tests must demonstrate high specificity to minimize false-positives, unnecessary diagnostic evaluations, and the psychological burden associated with uncertain results. Most importantly, they must provide evidence of improved patient outcomes to justify additional screening, either through reductions in cancer mortality or, as a shorter-term end point, through a clinically meaningful stage shift in cancers detected by MCED testing compared with standard-of-care (SOC) approaches alone. Although these tests have shown excellent specificity and minimal lasting psychosocial harm in prospective studies, their benefit to patient outcomes has not yet been established.^2,3

What clinical evidence exists to support the use of MCED tests in oncology practice?

Few prospective studies have evaluated the benefits, harms, and implementation of MCED tests in general‑risk populations. The most recent large studies attempting to establish clinical evidence are the PATHFINDER 2 study (NCT05155605) and the NHS-Galleri trial (NCT05611632; ISRCTN91431511).

The PATHFINDER 2 study evaluated the Galleri MCED test in 35,878 asymptomatic participants 50 years and older. The initial results of this study were presented at the 2025 European Society for Medical Oncology Congress and indicated that, during the study follow-up period, 200 participants were diagnosed with cancer. Of these, 133 were diagnosed after a positive Galleri test result, and 20 were diagnosed through SOC screening. Among cancers detected following a positive Galleri result, 53.5% were stages I or II and 73% were cancers detected without an existing recommended screening test. The test demonstrated a specificity rate of 99.6% (95% CI, 99.5%-99.7%), and the positive predictive value rate was 61.6% (95% CI, 54.9%-67.8%) (Figure).⁴

Some of the most consequential clinical evidence to date for an MCED test comes from the landmark NHS‑Galleri trial. Topline results from this trial have drawn widespread attention. In this large, randomized study involving more than 142,000 asymptomatic participants aged 50 to 77 years, annual multicancer screening with the Galleri test did not meet the trial’s prespecified primary end point of a statistically significant reduction in combined stage III to IV cancer diagnoses when added to standard screening over 3 years.⁵ However, full statistical analyses of the trial have not been released. According to a news release, the test detected approximately 4 times as many cancers as SOC testing alone, and fewer late-stage (stage IV) cancers were observed over time among those who received the test,⁵ which is encouraging. The scientific and clinical communities are eagerly awaiting more information about the trial so the measure of success (or failure) can be appropriately interpreted and contextualized.

What is the current state of MCED testing in oncology clinical practice?

On February 3, 2026, the Nancy Gardner Sewell Medicare Multi-Cancer Early Detection Screening Coverage Act established a pathway for Medicare to cover FDA-approved MCED tests.⁶ This legislation may also encourage the clinical trials needed to generate robust outcome data, including cancer-specific and overall mortality reduction data. Such evidence will be essential for FDA approval and for informing future screening recommendations, although the timeline for any test to reach this benchmark remains uncertain. Although the broader scientific and clinical community awaits definitive clinical evidence needed for FDA approval, MCED tests are being made available to consumers as laboratory-developed tests, potentially leading to an increasing number of individuals in the US receiving MCED tests and requiring a diagnostic workup for a suspected malignancy.

Accordingly, in 2023, Dana‑Farber Cancer Institute launched an MCED program dedicated to evaluating patients with positive MCED test results. Among the first 14 patients evaluated, 78.6% were diagnosed with cancer, including 6 with solid tumors and 5 with hematologic malignancies. Most of these cancers (90.9%) did not have existing screening options, and more than half (54.5%) of these cancers were stage I or II. Many patients accessed testing through employer benefits, insurance programs, or direct‑to‑consumer channels, and 64.3% self‑referred after finding the program online or through word of mouth. A detailed description of workup and diagnostic outcomes for the first subset of patients with positive MCED tests evaluated in our clinical program was published in March 2026.⁷

The Dana‑Farber program is also focused on advancing MCED research in high‑risk populations through investigator‑initiated studies aimed at better defining the clinical utility of MCED testing. The INFORM study (NCT06450171) is evaluating the Galleri test in approximately 1000 individuals with germline predisposition syndromes or significant family histories of cancer.⁸ The Sentinel study (NCT06523868), a decentralized effort funded by the US Department of Defense, is screening approximately 1500 veterans 45 years and older who have completed at least 4 years of service.⁹ The DISCOVER study (NCT07390643) is assessing the performance of MCED testing alongside standard diagnostic evaluations in approximately 100 patients presenting with signs or symptoms suggestive of cancer.¹⁰

MCED testing is also beginning to enter clinical practice, and new pathways for diagnostic evaluation following a positive test are rapidly evolving. The field holds significant promise across clinical, translational, and basic cancer research. Recent policy changes may accelerate the development of the evidence needed for FDA approval and broaden access through Medicare coverage. Despite this progress, substantial work remains to define appropriate use, ensure equitable implementation, and determine the most efficient strategies for evidence of clinical utility. Traditional pivotal trials require large cohorts, long follow‑up, and substantial cost, suggesting that new approaches to evidence generation may be necessary as the field advances.

References

1. Ofman JJ, Dahut W, Jemal A, et al. Estimated proportion of cancer deaths not addressed by current cancer screening efforts in the United States. Cancer Biomark. 2025;42(1):18758592241308754. doi:10.1177/18758592241308754
2. Schrag D, Beer TM, McDonnell CH III, et al. Blood-based tests for multicancer early detection (PATHFINDER): a prospective cohort study. Lancet. 2023;402(10409):1251-1260. doi:10.1016/S0140-6736(23)01700-2
3. Nadauld L, McDonnell CH III, Dilaveri CA, et al. Psychosocial impact associated with a multicancer early detection test (PATHFINDER): a prospective, multicentre, cohort study. Lancet Oncol. 2025;26(2):165-174. doi:10.1016/S1470-2045(24)00645-4
4. Nabavizadeh N, McDonnell C III, Kurbegov D, et al. LBA64 safety and performance of a multi-cancer early detection (MCED) test in an intended-use population: initial results from the registrational PATHFINDER II study. Ann Oncol. 2025;36(suppl 2):S1605. doi:10.1016/j.annonc.2025.09.076
5. Landmark NHS-Galleri trial demonstrates a substantial reduction in stage IV cancer diagnoses, increased stage I and II detection of deadly cancers, and four-fold higher cancer detection rate. News release. GRAIL Inc. February 19, 2026. Accessed April 8, 2026. https://grail.com/press-releases/landmark-nhs-galleri-trial-demonstrates-a-substantial-reduction-in-stage-iv-cancer-diagnoses-increased-stage-i-and-ii-detection-of-deadly-cancers-and-four-fold-higher-cancer-detection-rate/
6. Exact Sciences applauds passage of legislation establishing Medicare coverage pathway for multi-cancer early detection tests. News release. Exact Sciences Corp. February 2, 2026. Accessed April 8, 2026. https://www.exactsciences.com/news-events/press-releases/exact-sciences-applauds-passage-of-legislation-establishing-medicare-coverage-pathway
7. O'Donnell EK, Kauffman TL, Asnis S, et al. Diagnostic outcomes among patients with positive multi-cancer early detection test results. Cancer Res Commun. 2026;6(3):511-515. doi:10.1158/2767-9764.CRC-25-0723
8. Evaluation of multi-cancer early detection testing in a high-risk population: the INFORM study. ClinicalTrials.gov. Updated January 20, 2026. Accessed April 8, 2026. https://clinicaltrials.gov/study/NCT06450171
9. Evaluation of multi-cancer early detection testing in a high-risk military population: the Sentinel study. ClinicalTrials.gov. Updated February 27, 2026. Accessed April 8, 2026. https://clinicaltrials.gov/study/NCT06523868
10. The DISCOVER study (DISCOVERY). ClinicalTrials.gov. Updated February 5, 2026. Accessed April 8, 2026. https://clinicaltrials.gov/study/NCT07390643