A Blood Test for Early Cancer Detection Sparks Debate

Scientists have long dreamed of spotting cancers with a simple blood test in people who haven't shown symptoms.

One company says that day is here—though it has yet to convince government regulators.

Pathway Genomics began marketing a blood test in mid-September that it says can detect DNA fragments linked to 10 common cancers in otherwise healthy people. Consumers can order the test directly from the company’s website by consulting with Pathway physicians and completing a questionnaire.

But many cancer experts—and competitors—say the Pathway test is far from scientifically proven and could cause unnecessary alarm.

“This test is essentially telling you, ‘You’ve got cancer!’ But it can’t be linked to a particular site in the body or tell you whether the cancer may be problematic now or in the future,” says J. Leonard Lichtenfeld, deputy chief medical officer of the American Cancer Society.

The Food and Drug Administration has raised concerns, too. The agency sent a letter to Pathway’s CEO last week saying: “We believe you are offering a high risk test that has not received adequate clinical validation and may harm the public health.”

The agency gave Pathway 15 days to respond. Pathway said in a statement, “We are carefully considering the concerns of the FDA as stated in their letter, and we will be responding to that letter.”

Pathway officials say the company’s test is designed for people who are at high risk for cancer due to family history, an inherited genetic mutation or exposure to known carcinogens, such as years of heavy smoking. They also say it isn’t meant to diagnose cancer, but as a screening test to indicate whether more tests are warranted.

Pathway, a privately held diagnostics company based in San Diego, also says its test, called CancerIntercept Detect, should be classified as a laboratory developed test that it contends requires no FDA approval. (Beyond this case, the agency says it does have authority over the rapidly growing field.)

Other biotech firms are also racing to develop tests that can look for fragments of abnormal DNA shed by cancer cells into blood, urine, saliva and other body fluids. Most such “liquid biopsies” are being used in patients already diagnosed with cancer. They can help doctors assess whether a treatment is working or if a tumor has metastasized, without subjecting patients to extensive imaging or more surgery.

Using liquid biopsies to detect cancers before they cause symptoms is more controversial—in part because it’s unclear what the results mean. There is growing recognition in the medical community that not all cancers are destined to be deadly, and that many people may be undergoing debilitating treatments unnecessarily for abnormalities that might never cause harm. Cancers diagnosed early are easier to defeat than those found later and larger, but they are also more likely not to have required treatment at all.

Pathway executives hope that doctors will make the test—which they call “a cancer stethoscope”—part of routine checkups for high-risk patients. Pathway offers a subscription plan for repeat users: four tests a year for $299 each or $499 for an annual test, compared with $699 for a single test.

Still, it’s unclear what finding those mutations means. The test can’t distinguish which kind of cancer the abnormal DNA came from. Mutations in the KRAS gene, for example, are found in 57% of pancreatic cancers, 36% of colon cancers and in smaller amounts in lung, endometrial, ovarian, gastric, prostate, testicular and thyroid cancer, according to published research.CancerIntercept Detect scans the patient’s blood sample, looking for the absence or presence of 96 different mutations in nine specific genes that have been associated with several common cancers.

What’s more, the presence of such mutations does not necessarily indicate cancer. They could be associated with benign conditions, or a temporary error in cell replication that the body’s immune system gets rid of before it causes problems. And a negative test doesn't insure that the patient is cancer-free.

Pathway officials say that’s why the company insists on sending the results to patients’ physicians, who can interpret the results for them. “If the test finds abnormal DNA, the next step is to perform an imaging study and look hard to find a lesion,” says Glenn Braunstein, Pathway’s chief medical officer. “I wouldn’t advise treating anybody on the basis of this test alone.”

But some cancer doctors say they would be stumped by such test results. “If it’s not an obvious cancer, do we order a full body CT scan? Where do we even start to look?” asks the American Cancer Society’s Dr. Lichtenfeld.

Interpreting the results is also challenging because there is little published data to evaluate how the test performs with large groups of people. Pathway cites external research showing that the mutations it checks for are present in varying percentages of people with cancer. But there are no large studies showing how often those mutations are found in the general population, and how often they eventually correlate with a cancer diagnosis.

“No test is 100% sensitive or 100% specific. You are always going to have false positives and false negatives,” Dr. Braunstein says. Pathway hasn't disclosed how many tests have been ordered to date.Pathway officials say they have done internal studies on those questions that haven't yet been published.

The FDA’s letter to Pathway CEO Jim Plantesaid it was unclear how the research the company cites “is adequate to support the expansive claims.”

Pathway received a similar letter from the FDA in 2010 when it planned to market genetic test kits directly to consumers through Walgreensdrugstores, saying the kits required marketing approval from the agency. The company says that since 2010, the lab tests it performs have been ordered and reviewed by a qualified healthcare provider.

Cancer experts, academic researchers and biotech firms hold out great hope that sampling tumor fragments in body fluids can help understand and treat cancer.

The technology is advancing rapidly. A company called Trovagene Inc. has developed a urine-based test that allows doctors to track how lung cancers respond to treatment. A new blood test from Personal Genome Diagnostics can detect a specific mutation that predicts whether a pancreatic cancer is likely to respond to treatment.

“There’s a lot of excitement around what kinds of questions we can answer with this technology that we couldn’t answer before,” says Luis Diaz, a physician and cancer researcher at Johns Hopkins University who founded Personal Genome Diagnostics. “Now, we have to do the heavy lifting to prove that it’s safe and effective and will make a difference in people’s lives.”

To read the original article on The Wall Street Journal.com, please click here.