A trial for a multi-cancer screening test accurately detected cancer, often before symptoms arose, according to a new US study published today.
The research, published in the Annals of Oncology, says the test has a very low false positive rate and predicted where in the body the cancer is located with a high degree of accuracy. This, say the authors, could help doctors choose effective diagnostic tests.
The test is capable of detecting cancers that do not have screening tests available, such as liver, pancreatic and oesophageal cancers, for which early detection could make a real difference.
GRAIL, Inc., the California-based company that developed and funded the Circulating Cell-free Genome Atlas (CCGA) study, has made the multi-cancer early detection test available in the USA by prescription only, and to complement existing screening methods for breast, cervical, prostate, lung and bowel cancers.
First author Dr Eric Klein, chairman of the Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, said: “Finding cancer early, when treatment is more likely to be successful, is one of the most significant opportunities we have to reduce the burden of cancer.
“These data suggest that, if used alongside existing screening tests, the multi-cancer detection test could have a profound impact on how cancer is detected and, ultimately, on public health.”
The test involves taking a blood sample and analysing it for cell-free DNA (cfDNA), which tumours and other cells shed into the blood.
Genomic sequencing is used to detect methylation and a classifier developed with artificial intelligence uses these results to detect abnormal methylation patterns that suggest cancer is present.
The machine learning classifier can also predict where in the body the cancer is located. Results are available within ten business days from the time the sample reaches the lab.
The third and final sub-study of the study investigated the performance of the test in 2,823 people already diagnosed with cancer and 1,254 people without cancer.
It detected cancer signals from more than 50 different types of cancer and found that across all four cancer stages, the test correctly identified when cancer was present in 51.5% of cases. The test’s specificity was 99.5%, which means there was a false positive rate in 0.5% of cases.
Sensitivity of the test was 67.6% overall across stages I-III in 12 pre-specified cancers – anal, bladder, bowel, oesophageal, stomach, head and neck, liver and bile duct, lung, ovarian and pancreatic cancers, lymphoma and cancers of white blood cells such as multiple myeloma – and it was 40.7% overall in more than 50 cancers.
For all cancers, detection improved with each cancer stage with a sensitivity rate of 16.8% at the early stage I, 40.4% at stage II, 77% at stage III and 90.1% at stage IV.
The trial found that in solid tumours with no screening options, such as oesophageal, liver and pancreatic cancers, overall sensitivity of the test was twice that for solid tumours that do have screening options, such as breast, bowel, cervical and prostate cancers: 65.6% compared to 33.7%.
Overall sensitivity in cancers of the blood, such as lymphoma and myeloma, was 55.1%.
The multi-cancer early detection test correctly identified the tissue in which the cancer was located in the body in 88.7% of cases.
Dr Klein said: “We believe that cancers that shed more cfDNA into the bloodstream are detected more easily. These cancers are also more likely to be lethal, and prior research shows that this multi-cancer early detection test more strongly detects these cancer types. Cancers such as prostate shed less DNA than other tumours, which is why existing screening tests are still important for these cancers.”
The researchers estimated its positive predictive value (PPV) as well as the negative predictive value (NPV) and found PPV was 44.4% among people most likely to develop cancer, those aged 50-79, and the NPV was 99.4%.
“These data add to a growing body of literature that supports the use of next-generation sequencing for the detection of cell-free DNA in blood samples as a tool for earlier detection of common cancers that account for a significant number of deaths and other health problems worldwide,” said Dr Klein.
“In addition, a screening test that requires only a simple blood draw could provide an option for communities that have poor access to medical facilities. I’m excited about the potential impact this approach will have on public health.”
The journal editor in chief, Professor Fabrice André, Director of Research at the Institut Gustave Roussy, Villejuif, France, said: "Early detection of cancer is the next frontier in cancer research as it could save millions of lives worldwide. Developing technologies that address this issue is the first step. Next steps will include the development of new therapeutic interventions.
“In parallel, major efforts related to population awareness must continue or all these efforts will not lead to transformation of outcomes."
Klein E, Richards D, Cohn A et al. Clinical validation of a targeted methylation-based multi-cancer early detection test using an independent validation set. Annals of Oncology 24 June 2021
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