Hypewatch: Journalists need to pour some cold water into that “Grail”

Imagine how wonderful it would be if a test from a single blood drawing could tell you whether you had evidence of cancer long before symptoms appeared and presumably early enough for effective treatment. Wonder no more, suggests a report from Bloomberg News. Illumina, a genetic sequencing company, has formed a new company — somewhat hubristically named “Grail” — with funding from some notables including Jeff Bezos and Bill Gates. The announcement includes a statement from Illumina’s CEO, Jeff Flatley, that the $1000 test will be available in 2019.

The science behind such an endeavor is a bit overwhelming for me to even ponder. The Bloomberg story notes: “The challenges to creating such a test are daunting because the technology is new and companies will have to prove that they can catch and track cancer cells as accurately as traditional methods if they hope to upend standard procedures.”

Can these challenges be overcome? Let’s recall that a number of tests that would have been called pure fiction a decade ago are now routinely in use:

• Tests for BRCA1 and BRC2 mutations that increase the risk of ovarian and breast cancer
• Immunophenotyping of cells for the diagnosis, staging and response to treatment of a number of blood cancers including leukemias, lymphomas, myelodysplastic syndromes, and myeloproliferative disorders
• DNA screening of stool samples for rectal cancer

But as amazing as they are, these tests are nowhere near the level of complexity of what is being proposed. Grail proposes to develop a “pan screening” test. It is unclear what is exactly meant by that, but presumably they are not talking about a single cancer type or even a small number of differentiated cancers. “Pan” suggests that all cancers would be detectable with this test.

The Bloomberg report does speak to the need for the test to be both highly specific and highly sensitive. “A false positive could cause undue patient anxiety, while a false negative could lead a patient’s cancer to go untreated.” What the story doesn’t point out is that the degree of both sensitivity and specificity will need to be extraordinarily high. Pathway Diagnostics, referred to briefly in the Bloomberg article, attempted to market a blood test direct to consumers and was chided by the Food and Drug Administration in a warning letter “…for marketing a liquid biopsy test to healthy consumers and saying it could help them detect cancer early.” The FDA said the test hadn’t been validated by science. Pathway said it has “performed appropriate validation of the test as a laboratory developed test” and is doing more studies. I suspect that the definition of “appropriate” being used by Pathway may be a bit different than that used by the FDA. Pathway is not the first and not the only entrant into the genetic testing market to run afoul of the FDA.

Assuming that Grail can actually live up to its CEO’s expectations, there are still many questions to sort out. Who should be tested? When and what should be the interval between testing? What about follow up tests or diagnostic procedures? Since the test is said to be able to catch numerous different cancers, the follow up for each will be dramatically different. For some, follow up might include earlier or more frequent surveillance such as mammograms or colonoscopy. For some other types, more invasive testing might be needed.

But what are the downsides to wide spectrum blood testing? As noted above, Bloomberg dutifully mentions the possibility of false-negative and false-positive results. But what about detecting and treating cancers that may never pose a problem to the patient? As we’ve learned from experience with ductal carcinoma in situ (DCIS) and early-stage prostate cancer, the downsides of finding and treating some cancers may outweigh the benefits. Can we be sure that the very early-stage cancers detected by the test wouldn’t be better left alone to grow slowly or perhaps be eliminated by the body’s own immune defenses?

Bloomberg’s reporting doesn’t touch on this critical issue, perhaps because the only sources quoted are enthusiastic company representatives.

The science behind genetic testing is exciting and will likely revolutionize medicine in ways that we probably cannot imagine at the moment. But that excitement should not absolve journalists from reporting in a thorough and tempered fashion. By now we should have learned something about unfettered screening diagnostics.

Harold J. DeMonaco is one of our most prolific story reviewers and a frequent contributor to the HealthNewsReview.org blog.