Biotech startups worldwide are rushing to market screening tests that they claim can detect various cancers in early stages with just a few drops of blood. The tests allegedly will simplify cancer care by eliminating tedious scans, scopes, and swabs at the doctor’s office.
The promise of these early detection tests is truly “enticing,” Hilary A. Robbins, PhD, from the International Agency for Research on Cancer of the World Health Organization in Lyon, France, said in an interview.
In an opinion article in The New England Journal of Medicine, she emphasized that the new cancer tests are much less cumbersome than traditional screening strategies for individual cancers. Moreover, they could enable the early detection of dozens of cancer types for which no screening has been available so far.
Meeting the Criteria
The problem is that these tests have not met the strict criteria typically required for traditional cancer screening tests. To be considered for introduction as a screening procedure, a test usually needs to meet the following four minimum requirements:
- The disease that the test screens for must have a presymptomatic form.
- The screening test must be able to identify this presymptomatic disease.
- Treating the disease in the presymptomatic phase improves prognosis (specifically, it affects cancer-specific mortality in a randomized controlled trial).
- The screening test is feasible, and the benefits outweigh potential risks.
“The new blood tests for multiple cancers have so far only met the second criteria, showing they can detect presymptomatic cancer,” Dr. Robbins wrote.
The next step would be to demonstrate that they affect cancer-specific mortality. “But currently, commercial interests seem to be influencing the evidence standards for these cancer tests,” said Dr. Robbins.
Inappropriate Endpoints?
Some proponents of such tests argue that, unlike for previous cancer screening procedures, initial approval should not depend on the endpoint of cancer-specific mortality. It would take too long to gather sufficient outcome data, and in the meantime, people would die, they argue.
Eric A. Klein, MD, from the Glickman Urological and Kidney Institute in Cleveland, Ohio, and colleagues advocate for alternative endpoints such as the incidence of late-stage cancer in an article published in Cancer Epidemiology, Biomarkers & Prevention.
“The concept would be,” they wrote, “that a negative signal would not indicate a mortality benefit, leading to the study being stopped. A positive signal, on the other hand, could result in provisional approval until mortality data and real-world evidence of effectiveness are available. This would resemble the accelerated approval of new cancer drugs, which often is based on progression-free survival until there postmarketing data on overall survival emerge.”
Dr. Klein is also employed at the US biotech start-up Grail, which developed the Galleri test, which is one of the best-known and most advanced cancer screening tests. The Galleri test uses cell-free DNA and machine learning to detect a common cancer signal in more than 50 cancer types and predict the origin of the cancer signal. Consumers in the United States can already order and perform the test.