In a prospective study (SYMPLIFY) reported in The Lancet Oncology, Nicholson et al found that a circulating tumor DNA methylation-based multicancer early detection diagnostic test showed promise in predicting a diagnosis of cancer in symptomatic patients referred from primary care for investigation.
Study Details
In the study, patients aged ≥ 18 years were referred to National Health Service hospital sites in England and Wales with nonspecific symptoms or symptoms potentially due to gynecologic, lung, or upper or lower gastrointestinal cancers, and gave blood samples upon attendance for urgent investigation. A total of 5,461 eligible patients with an evaluable multicancer early detection test result and diagnostic outcome on standard-of-care investigation enrolled between July and November 2021 were included in the analysis.
Key Findings
Among the 5,461 eligible patients, 368 (6.7%) had a cancer diagnosis and 5,093 (93.3%) did not have a cancer diagnosis. The multicancer early detection test detected a cancer signal in 323 patients; cancer was diagnosed in 244 of these patients. The test had a positive predictive value of 75.5% (95% confidence interval [CI] = 70.5%–80.1%), a negative predictive value of 97.6% (95% CI = 97.1%–98.0%), a sensitivity of 66.3% (95% CI = 61.2%–71.1%), and a specificity of 98.4% (95% CI = 98.1%–98.8%).
Sensitivity of the multicancer early detection test increased with increasing cancer stage: 24.2% (95% CI = 16.0%–34.1%) in stage I; 57.1% (95% CI = 44.0%–69.5%) in stage II; 85.2% (95% CI = 77.1%–91.3%) in stage III; and 95.3% (95% CI = 88.5%–98.7%) in stage IV.
In cases where multicancer early detection testing detected a cancer signal among patients with cancer, the multicancer early detection test prediction of the site of origin was accurate in 85.2% (95% CI = 79.8%–89.3%) of cases, ranging from 71.7% (95% CI = 58.4%–82.2%) for cancers diagnosed by the lung pathway to 93.8% (95% CI = 86.5%–97.5%) for the lower gastrointestinal pathway.
Among patients diagnosed with cancer, multicancer early detection test sensitivity (80.4%, 95% CI = 66.1%–90.6%) and negative predictive value (99.1%, 95% CI = 98.2%–99.6%) were highest for patients with symptoms indicating investigation for upper gastrointestinal cancers. Sensitivities for other cancer sites included 70.8% for colorectal cancers, 67.9% for lung cancers, and 64.3% for ovarian cancers.
The investigators concluded, “This first large-scale prospective evaluation of a multicancer early detection diagnostic test in a symptomatic population demonstrates the feasibility of using a multicancer early detection test to assist clinicians with decisions regarding urgency and route of referral from primary care. Our data provide the basis for a prospective, interventional study in patients presenting to primary care with nonspecific signs and symptoms.”
Mark R. Middleton, PhD, of the Department of Oncology, University of Oxford, is the corresponding author for The Lancet Oncology article.
Disclosure: The study was funded by GRAIL Bio UK. For full disclosures of the study authors, visit thelancet.com.
