MCED: A New Screening Paradigm?

How effective is cancer screening? In the US alone, it’s estimated to have saved as many as 16.2 million years of life and up to $8.6 trillion in healthcare costs since the US Preventive Services Task Force (USPSTF) first published its screening recommendations.¹ But with perfect adherence, it might be possible to save five million more years and nearly $3 trillion extra—even before taking into account the potential gains of screening for additional cancer types.

Unfortunately, many patients are hesitant to pursue traditional cancer screening and diagnostics because they are often viewed as uncomfortable,² inaccessible,³ or unnecessary⁴—and many cancers are missed because only a few types (including breast, lung, colorectal, prostate, and cervical cancers) have recommended routine screening protocols.⁵ Nonetheless, early diagnosis is key; survival rates drop sharply when cancer goes undetected until its later stages (see Figure 1 below).

In response to this need, the emerging field of multicancer early detection (MCED) is flourishing. These minimally invasive tests aim to increase cancer testing efficiency, expand our ability to detect cancers without a specific screening test, and lower barriers to screening. But can they truly deliver on that promise—and are they ready to take on the growing global burden of cancer?

MCED: the benefits…

Currently, only about 14 percent of cancers in the United States are detected by screening,⁷ driven in part by the underuse of existing screening options and in part by the lack of screening available for many cancers. Factors that discourage cancer screening include a lack of easy access to testing facilities, inability of un- or underinsured patients to afford testing, and hesitance around certain types of screening (such as cervical smears, colonoscopies, or stool testing).

MCED tests can help overcome many of these barriers. Because they generally employ easily accessible sample types such as blood, urine, or saliva, patients are less likely to be discouraged by the prospect of a painful or invasive procedure. “Liquid biopsy” samples can be collected in primary care settings such as doctors’ offices or pharmacies, by mobile services, or even via self-collection in the patient’s home—and the risks associated with the procedure are often lower than those of standard screening tests such as colonoscopies. Additionally, because one sample can be tested for many different types of cancer, patients are often attracted by the tests’ convenience and reassurance.

Although MCED technologies are still early in their development, the tests show promise, especially in combination with confirmatory testing for patients with positive results. The UK’s SYMPLIFY study—the first large-scale prospective test of such a diagnostic in symptomatic patients—revealed an overall sensitivity and specificity of 66.3 and 98.4 percent, respectively, with higher values in patients of older ages or with more advanced cancers.⁸ Furthermore, the MCED test correctly identified the cancer’s site of origin in 85.2 percent of cases. A US-based study demonstrated the utility of MCED tests in detecting cancers without routine screening protocols, with approximately two-thirds of detected cancers lacking population screening options.⁹ Case studies also show the value of such tests in identifying early-stage cancers before symptoms arise, enabling rapid intervention to reduce morbidity, mortality, and burden on the healthcare system.¹⁰

… and the downsides

Although MCED tests frequently report high sensitivity and specificity, real-world experience may differ. Some studies have found more false positives than true positives¹¹—results that require costly, time-consuming, and sometimes invasive follow-up testing and may cause anxiety and distress while patients await confirmation of a potentially life-changing diagnosis. False negative results can be equally problematic, giving patients a false sense of security that may prompt them to forgo other screening tests or ignore nonspecific symptoms.

Even when such a test correctly identifies early-stage disease, the cancer may be slow-growing or nonlethal and require no intervention beyond monitoring. Having such a cancer confirmed by MCED could result in patients’ receiving unnecessary treatment, seeking excessive follow-up testing, or experiencing mental health concerns as a result of the diagnosis. Some data suggest that MCED testing is more likely to detect large, fast-growing, or otherwise consequential cancers, but further investigation is required.¹²

Finally, although MCED tests are often less invasive and anxiety-inducing than standard screening procedures, many patients may find them financially inaccessible. Most of these tests are not currently covered by insurance, meaning that people must pay some or all of the cost out of pocket—and with prices as high as $1,000 per test, MCED is off the table for those who lack the resources to pursue it. Bills have been introduced in Congress to establish Medicare coverage for MCED screening;^13,14 private payers, however, are likely to set high standards for coverage, especially in cancers that already have alternative screening tests.¹⁵

The future of MCED

Major studies are planned in both the US and the UK to evaluate the promise of MCED testing. The UK’s National Health Service is currently evaluating GRAIL’s Galleri test, which screens for over 50 different cancers, in approximately 140,000 people aged 50 to 77.¹⁶ In the US, the National Cancer Institute’s Division of Cancer Prevention is implementing a preliminary study of approximately 24,000 healthy participants aged 45 to 70 to assess practical considerations around MCED testing, including patient adherence to testing and follow-up, workflow feasibility, reliability and timeliness of results, and barriers to participation.¹⁷ The study’s results will inform the design of future trials evaluating both MCED and other emerging screening approaches.

No MCED test has yet received FDA approval, although several have been granted Breakthrough Device designation or are currently regulated by CLIA as laboratory-developed tests.¹⁸ As manufacturers, regulatory bodies, and research groups continue to investigate the tests’ real-world possibilities, new technologies—such as spectroscopic liquid biopsy,¹⁹ novel analytes,²⁰ and artificial intelligence²¹—are continually changing the landscape of cancer detection. Is MCED the future of cancer diagnosis? Only time will tell—but it’s clear that the prospect warrants legislative, regulatory, and scientific attention.

References:

1. 1. Philipson TJ et al. The aggregate value of cancer screenings in the United States: full potential value and value considering adherence. BMC Health Serv Res. 2023;23(1):829. doi:10.1186/s12913-023-09738-4.

1. 1. Reynolds LM et al. Emotional predictors of bowel screening: the avoidance-promoting role of fear, embarrassment, and disgust. BMC Cancer. 2018;18(1):518. doi:10.1186/s12885-018-4423-5.

1. 1. Lofters AK et al. Care in the community: opportunities to improve cancer screening uptake for people living with low income. Prev Med Rep. 2021;24:101622. doi:10.1016/j.pmedr.2021.101622.

1. 1. Richman IB et al. Lost to follow up?: a qualitative study of why some patients do not pursue lung cancer screening. Prev Med Rep. 2022;29:101909. doi:10.1016/j.pmedr.2022.101909.

1. 1. American Cancer Society. American Cancer Society Guidelines for the Early Detection of Cancer. November 1, 2023. https://www.cancer.org/cancer/screening/american-cancer-society-guidelines-for-the-early-detection-of-cancer.html.

1. 1. US Cancer Statistics Working Group. US Cancer Statistics Data Visualizations. November 2023. https://gis.cdc.gov/Cancer/USCS/#/SurvivalbyStage.

1. 1. NORC at the University of Chicago. Percent of Cancers Detected by Screening. 2022. https://cancerdetection.norc.org.

1. 1. Nicholson BD et al. Multi-cancer early detection test in symptomatic patients referred for cancer investigation in England and Wales (SYMPLIFY): a large-scale, observational cohort study. Lancet Oncol. 2023;24(7):733–743. doi:10.1016/S1470-2045(23)00277-2.

1. 1. Westgate C et al. Early real-world (RW) experience with a multi-cancer early detection (MCED) test. J Clin Oncol. 2023;41(16):10519. doi:10.1200/JCO.2023.41.16_suppl.10519.

1. 1. Vittone J et al. A multi-cancer early detection blood test using machine learning detects early-stage cancers lacking USPSTF-recommended screening. NPJ Precis Oncol. 2024;8(1):91. doi:10.1038/s41698-024-00568-z.

1. 1. Schrag D 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.

1. 1. Multicancer Early Detection Consortium. Evaluating the Clinical Utility of Multi-Cancer Early Detection (MCED) Tests: Envisioning A Path Forward. September 2023. https://www.aonnonline.org/images/resources/navigation_tools/Evaluating-the-Clinical-Utility-of-MCED.pdf.

1. 1. H.R.2407 – Nancy Gardner Sewell Medicare Multi-Cancer Early Detection Screening Coverage Act. Congress.gov. March 30, 2023. https://www.congress.gov/bill/118th-congress/house-bill/2407/text.

1. 1. S.2085 – Medicare Multi-Cancer Early Detection Screening Coverage Act. Congress.gov. June 21, 2023. https://www.congress.gov/bill/118th-congress/senate-bill/2085/text.

1. 1. Trosman JR et al. Perspectives of private payers on multicancer early-detection tests: informing research, implementation, and policy. Health Aff Scholar. 2023;1(1):qxad005. doi:10.1093/haschl/qxad005.

1. 1. Neal RD et al. Cell-free DNA-based multi-cancer early detection test in an asymptomatic screening population (NHS-Galleri): design of a pragmatic, prospective randomised controlled trial. Cancers (Basel). 2022;14(19):4818. doi:10.3390/cancers14194818.

1. 1. National Cancer Institute. Preliminary Vanguard Study. https://prevention.cancer.gov/major-programs/cancer-screening-research-network-csrn/preliminary-vanguard-study.

1. 1. Rubinstein WS et al. Cancer screening with multicancer detection tests: a translational science review. CA Cancer J Clin. 2024; online ahead of print. doi:10.3322/caac.21833.

1. 1. Cameron JM et al. A spectroscopic liquid biopsy for the earlier detection of multiple cancer types. Br J Cancer. 2023;129(10):1658–1666. doi:10.1038/s41416-023-02423-7.

1. 1. Bratulic S et al. Noninvasive detection of any-stage cancer using free glycosaminoglycans. Proc Natl Acad Sci USA. 2022;119(50):e2115328119. doi:10.1073/pnas.2115328119.

1. 1. Eledkawy A et al. Precision cancer classification using liquid biopsy and advanced machine learning techniques. Sci Rep. 2024;14(1):5841. doi:10.1038/s41598-024-56419-1.