The SYMPLIFY study was the first large-scale evaluation of a multi-cancer early detection (MCED) test in individuals who presented to their GP for diagnostic follow-up for suspected cancer. The observational study, led by Associate Professor Brian Nicholson (Nuffield Department of Primary Care Health Sciences), trialled US healthcare company GRAIL’s MCED test in more than 5,400 people who were referred for urgent cancer investigations through the NHS.
MCED tests work by analysing biological signals in the blood that may indicate the presence of cancer. Importantly, they may also predict where in the body the cancer is likely to have originated, allowing direction to the most appropriate cancer pathway for onward investigation.
In this follow-up work published in the Lancet Regional Health - Europe, data were collected on the cancers that were diagnosed in SYMPLIFY study participants in the two years following the original study. By comparing these data with the original MCED test results, symptoms and referral pathways, the researchers found that nearly one in five cancers diagnosed during the study might have been identified more efficiently if clinicians had been able to use the MCED test results to guide investigations.
“The findings suggest these tests could help some patients receive a diagnosis sooner and potentially reduce the complexity of the diagnostic journey, particularly for cancers that are difficult to identify or present with non-specific symptoms,” said Associate Professor Brian Nicholson.
The researchers also discovered that a significant proportion of patients initially thought to have received a “false positive” test result were later diagnosed with cancer. Of 79 patients whose positive MCED test result was not matched by an immediate diagnosis (apparent false positive results), 28 (35%) were subsequently found to have cancer within two years. Conversely, of the 5014 patients with a negative MCED test result and no cancer reported during the SYMPLIFY study, only 113 patients (2%) were subsequently diagnosed with cancer in the 2 years following. Most of these cancers were unlikely to be related to the initial presentation of symptoms, suggesting they may have developed since the SYMPLIFY study rather than being missed.
“Our analysis suggests that a positive MCED test result may sometimes identify cancers that are not yet detected through standard investigations,” said Associate Professor Nicholson. “This highlights the need to better understand how these tests could be incorporated into clinical pathways and how patients with positive results should be followed up.”
The study also identified limitations. Researchers found that relying only on the blood test could potentially have delayed diagnosis in 49 cases if the test incorrectly predicted the cancer's location. The authors stress that MCED tests should be considered as an additional tool to support, rather than replace, clinical judgement and conventional investigations. Further studies are needed to determine how best to use the technology in routine healthcare and whether it can improve outcomes for patients.