In April, television viewers heard in an advertisement for Cologuard: “Even though you’re stuck at home, you can still be screened for colon cancer.” The commercial spot, which aired on major networks like CNN and NBC, let people know that despite the COVID-19 pandemic, Exact Sciences, which makes the test, was still open for business. The campaign is one of many the company has launched in recent years to boost attention and interest in its flagship product, Cologuard. Since gaining FDA approval in 2014, Cologuard has emerged as an alternative to colonoscopy to screen average-risk patients for colon cancer. The multitarget stool DNA test (mt-sDNA) analyzes fecal samples for strands of cancerous or precancerous DNA. Many gastroenterologists welcome the test as a way to expand screening to more people, but think the noninvasive test will not be able to replace colonoscopy.

Beyond Colon Cancer

Based in Madison, Wis., Exact Sciences was founded in 1995, although it took about 15 years to get the fecal DNA test off the ground. In 2010, the company started publishing the results of a validation study for its test, and in 2011, it started enrolling patients in its Deep-C clinical trial, the “largest privately funded study of its kind for colorectal cancer screening,” according to the company’s website. In 2014, the FDA approved Cologuard for average-risk individuals.

The company has big aspirations, in colorectal cancer testing and beyond. To market Cologuard over the past six years, Exact Sciences sponsored a golf tournament with PGA Tour Champions (the Cologuard Classic) and partnered with Pfizer to promote Cologuard. Last year, Exact Sciences acquired Genomic Health, a genetic research company that developed the Oncotype DX genomic tests for breast, prostate and other types of cancer. Exact Sciences is working to develop tests for the 15 “deadliest” cancers, including liver and pancreatic, according to the company’s 2018 annual report. If all goes according to plan, the company eventually could become a one-stop shop of sorts for noninvasive cancer screening.

“We are striving to change lives across the cancer continuum—from earlier detection to treatment guidance and recurrence monitoring,” Kevin Conroy, JD, the CEO of Exact Sciences, wrote in an email to Gastroenterology & Endoscopy News. “Our goal is to extend our leadership position in cancer diagnostics over the next decade and beyond.”

The approach appears to be working for the company so far. Year over year, Cologuard continues to grow in popularity among providers, Mr. Conroy said. Providers are ordering Cologuard more and more often, with an 80% increase in patients tested via Cologuard in 2019 compared with 2018, he said. Since 2014, the company’s revenue has increased every year, nearly doubling from about $267 million in 2017 to $454 million in 2018, according to Exact Sciences’s 2018 annual report.

Although Exact Sciences seems to be thriving, it will need to avoid the legal and financial challenges other genetic testing firms, like Myriad Genetics, have faced in the past. Myriad has foundered in recent months during the COVID-19 pandemic, but had faced multiple problems before this year. In 2019, Myriad battled declining revenue as the company bowed to pricing pressures and a major drop in stock prices after the FDA questioned the validity of a new test, according to Barron’s. Several years earlier, the company lost a case in front of the Supreme Court after the judges decided human genes could not be patented, breaking the company’s monopoly on tests for the BRCA1 and BRCA2 genes, related to breast cancer.

“Is it disruptive? I would say absolutely,” Paul Limburg, MD, MPH, a gastroenterologist and the chief medical officer at Exact Sciences, said. “Is that a good thing or a bad thing? I don’t know. That’s probably open to interpretation.” Dr. Limburg could not predict whether Cologuard would overtake other colon cancer screening tests, but noted patients have expressed a preference for Cologuard. “I’m a firm believer that choice is a key component in participation in colorectal cancer screening.”

Lack of screening is one of the biggest obstacles in colorectal cancer treatment, the third most common type of cancer in the United States. About one in three adults aged 50 to 75 years in this country are not screened for colorectal cancer as advised by the American Cancer Society.

The molecular alterations that distinguish colon cancer and polyp cells from normal cells have been well described in the scientific literature for decades, but the technology to measure them noninvasively really only became possible about 10 years ago, according to John Kisiel, MD, a gastroenterologist at Mayo Clinic in Rochester, Minn., and the leader of an ongoing collaboration between Mayo Clinic and Exact Sciences. After a patient sends a stool sample to the company’s lab, the stool is homogenized and run through a centrifuge. Short pieces of DNA, called capture probes, are then added to the liquid that rises to the top of the sample to bind with specific DNA fragments, Dr. Kisiel said.

In these fragments, the test identifies mutations and methylation in three different genes (KRAS, BMP3 and NDRG4), as well as the presence of beta-actin as a “housekeeping” gene, he said. A mathematical model combines the results of this stool test with results from the patient’s fecal immunochemical test (FIT) to send the prescribing doctor a binary positive or negative result. All patients with a positive test are advised to get a diagnostic colonoscopy.

“Cologuard is certainly better than any of the other stool-based tests,” said Jerome Waye, MD, a professor emeritus at Mount Sinai in New York City, and a pioneer in colonoscopy. A new study Exact Sciences submitted to the 2020 Digestive Disease Week found that Cologuard outperforms FIT tests in terms of increased clinical benefit and reduced mortality from colorectal cancer (abstract Su1773). The researchers found that a patient needs twice as many FIT tests—21 versus nine—to match the number of life-years gained and colorectal cancer–related incidents avoided by screening with Cologuard.

Cologuard could be particularly useful in boosting screenings in rural areas and communities with limited access to colonoscopy, Dr. Waye said. The test also could be useful for adults between 45 and 50 years of age, who are now recommended to get screened, Dr. Limburg said. Many people in this age bracket are likely to still be working full-time in addition to caring for children or parents, which could make the demands of bowel preparation and time off from work for a colonoscopy particularly burdensome, he said.

But Cologuard cannot match colonoscopy, the current gold standard test, in its ability to detect adenomas, especially smaller ones, Dr. Waye said. “I think colonoscopy is going to continue to be the mainstay because polyps can be found and removed, and we can prevent colon cancer by taking out polyps with colonoscopy.”

“Overall, it’s very convenient,” Frederick Gandolfo, MD, a gastroenterologist at Precision Digestive Care on Long Island, N.Y., said of Cologuard. After all, the Cologuard test kit is mailed to a patient’s home and a patient navigator reminds patients to send in their samples. But Dr. Gandolfo said he primarily prescribes Cologuard for patients who don’t want or can’t undergo colonoscopy for medical reasons. Otherwise, colonoscopy is still the best option, he said, because it’s more preventive, and identified polyps can be removed during the procedure. Plus, with its relatively high false-positive rate (13%), Cologuard’s result can still lead to additional colonoscopies that may turn up polyps and lesions but not cancers. “I think Cologuard is not that cost-effective” at the moment, he said.

Still, although the test may not be as effective as colonoscopy, it may be more acceptable to patients. In February, Exact Sciences published a retrospective study in the Journal of Medical Screening examining its own data from a year of tests to see how often patients completed their prescribed test. For 368,000 tests ordered, patient adherence was 71%—a high number. Previous studies estimated adherence to colonoscopy screening around 38% and adherence to FIT around 42%. “People are more willing to complete this test than they are some of these other options,” Dr. Limburg said.

Before the COVID-19 pandemic, Dr. Gandolfo and many other gastroenterologists thought Cologuard would not drastically disrupt business as usual, while providing a welcome tool to expand screening to more patients. Despite the ad blitz informing people that Exact Sciences has remained fully open, Dr. Gandolfo was unconvinced the at-home nature of the test will give Cologuard an edge.

“While you can do a Cologuard during the shutdown, I haven’t been ordering them at this time,” Dr. Gandolfo told Gastroenterology & Endoscopy News. “The reason is that a positive result would still need to wait to have a diagnostic colonoscopy, which would just add needless anxiety for the patient while waiting for colonoscopy to become available again.”

—Jillian Mock