Diagnostics & Imaging Week

No matter how effective a test is, it isn't much good if not used.

That is the medical fact-of-diagnosis that Exact Sciences (Marlborough, Massachusetts) hopes to parlay into general use for its test as an alternative to colonoscopy.

Exact has just reported results of a new study conducted at the Mount Sinai School of Medicine (New York) showing that a refined and advanced-generation version of Exact's PreGen test for colorectal cancer detected 88% of cancers with a specificity of 82% across all stages of cancer, regardless of the location.

The basic PreGen test — a stool-based assay — distributed as a home-brew offering by Laboratory Corporation of America (LabCorp; Burlington, North Carolina), offers a sensitivity of about 72.5%, the study also demonstrated, according to Don Hardison, president/CEO of Exact Sciences.

"What we're showing is a couple of things: first of all, the test on the market today is sensitive and more sensitive than any other test on the market other than a colonoscopy," Hardison told Diagnostics & Imaging Week. "And [the test] also has a chance to be improved by changing the markers and changing the chemistry, which is something we've been saying anyway.

"As long as we were working with DNA, and we could continue to improve the assay, this [refined test] is an indication that that is, in fact, true." An "enhanced marker panel" using a refined DNA capture and stabilization process was developed for the test, Hardison noted.

The Mount Sinai study, titled "Improved Fecal DNA Test for Colorectal Cancer Screening," evaluated 162 patients, 40 individuals with cancer and 122 individuals with normal colonoscopies.

"This study confirms that stool-based DNA technologies can achieve high sensitivities for detecting colorectal cancer," said Steven Itzkowitz, MD, principal investigator and professor and associate director of gastroenterology at Mount Sinai School of Medicine.

For those over age 50 in the U.S., who resist the choice of the "gold standard" but seriously uncomfortable colonoscopy – or even virtual colonoscopy – Exact believes its DNA test for colorectal cancer offers an important alternative, and one that is non-invasive, perhaps its most important characteristic.

"For those patients who are unwilling or unable to undergo colonoscopy, stool DNA testing offers a valuable and patient-friendly screening option. These results also underscore that as new markers and technologies are developed and validated, they can readily be incorporated into existing stool DNA tests to improve cancer detection and, ultimately, patient outcomes," Itzkowitz said.

Currently, there are 84 million people in the U.S. above the age of 50, and a "huge number" of those individuals have not been screened for colon cancer, which is an ACS guideline, he said. He said the American Cancer Society (ACS; Atlanta) estimates that 40% to 50% have been screened, but that still leaves half or more of that group unscreened, despite the fact that screening methods like colonoscopy have been available for some time — with colonography made available more recently.

Viatronix' (Stony Brook, New York) V3DColon System was the first VC approved by the FDA for colon cancer screening in April 2004.

"We believe there's a need for new options and less invasive options like stool DNA testing," Hardison said. "And studies show that the commercial test that's on the market through LabCorp today — over half the people who've used that test have never been screened. So, we know we're bringing new people into the screening population."

Hardison noted that it is an ACS goal to have 70% of Americans over the age of 50 screened by the year 2015.

"This is one of the tests that will help make that a reality," he said.

In October, Exact reported that it was initiating a plan to reduce its cost structure by eliminating 21 positions across all departments, leaving it with 23 employees. The company said the reductions will extend its resources into 1Q09.

The restructuring initiative was reported less than a month after the American Cancer Society (Atlanta) and its Multi-Society Task Force failed to make any final recommendations on revised colorectal cancer screening guidelines, a move prompting the layoffs, according to a company executive.

The company said that the remaining employees would focus on the following key objectives: obtaining inclusion in colorectal cancer screening guidelines, obtaining Medicare coverage for stool-based DNA screening; and optimization and further validating the company's Version 2 technology.

Asked if he thought the latest study results would further the company's case toward a recommendation of DNA stool screening, Hardison offered less than a ringing certainty — "We hope so," he said.

Currently, the test is being offered through LabCorp as a "home-brew" test. While Hardison said that Exact Sciences would likely seek FDA approval for the test in the future, no specific timeframe had been determined to submit to the agency. However, he did say any submission to the FDA would likely involve the company's refined test that was studied by Itkowitz at Mount Sinai.

Exact uses applied genomics to develop screening technologies for use in the detection of cancer. Rather than discovering the biomarkers used in the assay, Hardison said the company has licensed biomarkers from researchers at institutions such as Case Western Reserve University (Cleveland) and Johns Hopkins (Baltimore).