Though a ‘work in progress,’ the Oxford researchers who conducted the trail believe the MCED blood test could help doctors give better cancer assessments
Cancer is typically diagnosed through tissue biopsies that are often invasive and painful for patients. Now, recently-released results of a National Health Service (NHS) trial study of a relatively new multi-cancer early detection test (MCED) may provide a less painful/invasive cancer test experience to UK residents.
Developed by California-based healthcare technology company Grail, the clinical laboratory blood test—called Galleri—can detect 50 cancer types and, according to the company’s website, even identify the cancer’s location within the body. It is currently only available through a doctor’s prescription.
Researchers have long sought to improve screening methods and diagnostic technologies that identify cancers more easily and at an earlier stage. They recognize that a simple, inexpensive laboratory blood test—as opposed to a tissue biopsy—that detects both the presence of multiple cancer types and its location would benefit both medical professionals and patients worldwide.
The NHS trial study of the Galleri MCED test—dubbed SYMPLIFY—began in 2021. It is “a collaboration between the University of Oxford’s Department of Oncology, the Cancer Research Group at the Nuffield Department of Primary Care Health Sciences, the Oncology Clinical Trials Office, and the Primary Care Clinical Trials Unit,” according a 2021 University of Oxford press release.
The researchers published their findings in The Lancet Oncology titled, “Multi-cancer Early Detection Test in Symptomatic Patients Referred for Cancer Investigation in England and Wales (SYMPLIFY): a Large-scale, Observational Cohort Study.”
“The [Galleri] test was 85% accurate in detecting the source of the cancer, and that can be really helpful because so many times it is not immediately obvious when you have got the patient in front of you what test is needed to see whether their symptoms are down to cancer,” said Mark Middleton, MD, PhD, head of the Department of Oncology at the University of Oxford and lead researcher of the study, in a BBC interview. (Photo copyright: University of Oxford.)
Details of the SYMPLIFY Study
To conduct the SYMPLIFY study, Oxford researchers enrolled 6,238 adults in England and Wales who were referred for imaging and diagnostic testing with symptoms that were indicative of gynecological, lung, or lower/upper GI cancers, or with non-specific symptoms. The most commonly reported symptoms that triggered the referrals were:
- Weight loss (24.1%)
- Change in bowel habits (22.0%)
- Post-menopausal bleeding (16.0%)
- Rectal bleeding (15.7%)
- Abdominal pain (14.5%)
- Pain (10.6%)
- Difficulty swallowing (8.8%)
- Anemia (7.1%)
DNA from cancer cells—called ctDNA (circulating tumor DNA)—can be detected in blood samples at early tumor stages. The Galleri MCED test was performed on cell-free DNA taken from blood samples provided by the study participants. The test was performed in batches and blinded to results of previous diagnostic tests.
The predictions of the test were then compared to diagnoses received via traditional diagnostic testing and imaging.
According to the Oxford researchers’ Lancet paper, GRAIL’s MCED test detected a cancer signal in 323 of the study participants. Of those individuals, 244 received a cancer diagnosis, resulting in a positive predictive value (PPV) of 75.5%, a negative predictive value (NPV) of 97.6%, and a specificity of 98.4%.
The overall sensitivity of the Galleri test was 66.3%, representing a range from 24.2% in Stage 1 cancers to 95.3% in stage IV cancers. The mean age of the study participants was 62.1 years old, and the sensitivity increased with age and cancer stage.
The overall accuracy of the top Cancer Signal Origin (CSO) prediction following a positive MCED test was 85.2%, the researchers concluded.
“With that prediction from the test, we can decide whether to order a scope or a scan and make sure we are giving the right test the first time,” Mark Middleton, MD, PhD, head of the Department of Oncology at the University of Oxford and lead researcher of the study, told BBC News.
The most common cancers detected among the study participants were:
“Earlier cancer detection and subsequent intervention has the potential to greatly improve patient outcomes. Most patients diagnosed with cancer first see a primary care physician for the investigation of symptoms suggestive of cancer, like weight loss, anemia, or abdominal pain, which can be complex as there are multiple potential causes,” said Brian Nicholson, DPhil, Associate Professor at Oxford’s Nuffield Department of Primary Care Health Sciences and co-lead investigator for the study in a 2023 Oxford press release. “New tools that can both expedite cancer diagnosis and potentially avoid invasive and costly investigations are needed to more accurately triage patients who present with non-specific cancer symptoms.
“The high overall specificity, positive predictive value, and accuracy of the cancer signal detected and cancer signal origin prediction that was reported across cancer types in the SYMPLIFY study indicate that a positive MCED test could be used to confirm that symptomatic patients should be evaluated for cancer before pursuing other diagnoses,” he added.
MCED Test May Help Doctors Better Assess Cancer
The SYMPLIFY study is the first large-scale analysis of an MCED test in patients who were referred by their doctors for diagnostic testing due to suspected cancers. The results of the study were presented at the annual meeting of the American Society of Clinical Oncology (ASCO) in June.
Middleton told BBC News that the test is not yet accurate enough to “rule in or rule out cancer,” but it was useful for researchers and patients.
“The findings from the study suggest this test could be used to support GPs to make clinical assessments but much more research is needed, in a larger trial, to see if it could improve GP assessment and ultimately patient outcomes,” David Crosby, PhD, head of Prevention and Early Detection Research, Cancer Research, UK, told BBC News.
Scientists at the University of Oxford were responsible for data collection, analysis, and interpretation of the data used for the study. The study was funded by GRAIL with support from National Health Service England (NHS), NHS Wales, the National Institute for Health and Care Research (NIHR), and the NIHR Oxford Biomedical Research Centre.
Clinical laboratories and anatomic pathology groups that perform tissue biopsy testing for oncologists will want to monitor the progress of this simple blood test that may someday reduce the number of invasive, painful biopsies required to diagnose cancer and other health considerations.