MCED (methylation-based multicancer early detection) Test Can Aid Cancer Diagnosis in Symptomatic Patients

A methylation-based multicancer early detection (MCED) test can aid cancer diagnosis in patients who present with non-specific symptoms, according to a study published in The Lancet Oncology.  “MCED test results can help assess the risk that a symptom is due to cancer, providing a means for primary care physicians to decide whom to urgently investigate,” the researchers wrote.

The researchers used the MCED test in 5461 patients with non-specific symptoms or symptoms potentially due to gynecologic, lung, or gastrointestinal cancers. The median age of patients was 61.9 years, and 66.1% were women.  The most common symptoms in these patients were unexpected weight loss (24.1%), change in bowel habits (22.0%), post-menopausal bleeding (16.0%), rectal bleeding (15.7%), abdominal pain (14.5%), and pain (10.6%).

Patients had blood samples taken, cell-free DNA was isolated, and the MCED test was performed.  The researchers compared MCED results with diagnoses made via standard care to determine the positive and negative predictive value, sensitivity, and specificity of the MCED test.  Cancer diagnoses were recorded in 368 patients (6.7%). The most common diagnoses were colorectal (37.2%), lung (22.0%), uterine (8.2%) and esophago-gastric (6.0%) cancers. About half (53%) of cancers were diagnosed as stage III or IV.

The MCED test detected a cancer signal in 323 patients, and 244 of those patients had a cancer diagnosis.  The test had a sensitivity of 66.3% and a specificity of 98.4%.  The test had its highest sensitivity (80.4%) and negative predictive value (99.1%) in patients with symptoms requiring investigation for upper gastrointestinal cancer.  “The moderate overall sensitivity suggests that a negative result using the current classifier would not be sufficient to deflect patients who already qualify for investigation on the basis of their clinical presentation, other than for upper gastrointestinal pathways,” the researchers wrote.

The sensitivity of the MCED test increased with increasing age and cancer stage, except in upper gastrointestinal cancer.  Overall, the sensitivity of the MCED test was 24.2% with stage I cancer and increased to 95.3% with stage IV disease.

The MCED test accurately predicted the site of origin for cancer in 85.2% of cases.  The researchers noted that “many cancers were diagnosed at sites other than those inferred by the symptoms that led to referral.”

“This first large-scale prospective evaluation of an MCED diagnostic test in a symptomatic population demonstrates the feasibility of using an MCED test to assist clinicians with decisions regarding urgency and route of referral from primary care,” the researchers wrote.  “Our data provide the basis for a prospective, interventional study in patients presenting to primary care with non-specific signs and symptoms.”

Disclosures:  This research was supported GRAIL Bio UK.  Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies.  Please see the original reference for a full list of disclosures.


Nicholson BD, Oke J, Virdee PS, et al. Multi-cancer early detection test in symptomatic patients referred for cancer investigation in England and Wales (SYMPLIFY): A large-scale, observational cohort studyLancet Oncol. Published online June 20, 2023. doi:10.1016/S1470-2045(23)00277-2

REFERENCE:  Cancer Therapy Advisor; 26 JUN 2023; Leah Lawrence