MCED Tests in Primary Care: Proceed With Caution

Medscape

a day ago

Hi, everyone. I'm Dr Kenny Lin. I am a family physician and associate director of the Lancaster General Hospital Family Medicine Residency, and I blog at Common Sense Family Doctor.
Kenneth W. Lin, MD, MPH
In the past decade or so that I have been giving lectures on cancer screening at family medicine review courses, not much has changed. We screen for breast, cervical, and colorectal cancer in large numbers of people. We screen for lung cancer in current or past smokers over 50 years of age with at least a 20 pack-year history. We discuss the potential benefits and harms of screening for prostate cancer with older males. But these five cancer types represent a distinct minority of cancers. A 2022 study estimated that only 1 in 7 diagnosed cancer cases in the United States are caught by any of these screening tests, and 57% of cancers have no recommended screening tests, meaning that they are usually not detected until advanced stages.
For the past few years, Grail has been selling a blood test that aims to fill the early detection gap by detecting cell-free DNA signals associated with cancer. At $949 per test, the Galleri test is advertised as being able to detect more than 50 cancer types in adults aged 50 years or older. Other companies are developing similar tests. If they haven't already, family physicians will soon be asked to order multicancer early detection (MCED) tests for patients or act on their results. So, what do we know about their benefits and harms? And what remains uncertain?
A systematic review published in May 2025 by the Agency for Healthcare Research and Quality found that the evidence for MCED tests consists mostly of diagnostic accuracy studies with suboptimal designs. A few prospective studies have shown that the tests are highly specific but have relatively low sensitivity for early-stage cancers. There is little data on harms such as false alarms, incidental findings, and unnecessary diagnostic procedures and treatments; in one study, patient-reported anxiety associated with a positive MCED result was small and returned to baseline by 12 months, regardless of whether cancer was confirmed.
To be effective, MCED tests must accurately detect cancer in asymptomatic people at stages early enough to decrease harm (by subjecting patients to less toxic cancer therapy) or increase benefits (by allowing patients to live longer or better). Already under-resourced primary care practices would need to develop new workflows to work up patients with positive tests and determine when to refer them to oncologists.
In a JAMA Internal Medicine Special Communication, screening experts argued that since MCED screening 'would entail tremendous costs and potentially substantial harms", it should not be implemented until a randomized trial reports it reduces all-cause mortality. Others feel that a trial showing fewer cancer-related deaths, such as one being planned by the National Cancer Institute, would be sufficient. An ongoing trial of Galleri in more than 140,000 UK National Health Service patients expects to report effects on cancer stage-shift (a reduction in late stage cancer diagnoses) as early as next year, though it appears to have failed to meet criteria for early indications of benefit.
Recognizing that diffusion of MCED tests into practice is outpacing the evidence, the American Cancer Society published a consensus statement to guide primary care clinicians. Important points include communicating uncertainty about benefits and harms, emphasizing that patients with negative results should continue to have all screenings recommended by the US Preventive Services Task Force, and first evaluating patients with positive results for cancer at the predicted tissue of origin (eg, mammography for breast cancer), then ordering total body PET-CT scans if the tissue of origin is unknown or the initial workup is unrevealing.