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New Colorectal Cancer Screening Guidelines From USPSTF May Benefit Exact Sciences' Cologuard

NEW YORK (GenomeWeb) – An updated recommendation statement on colorectal cancer screening from the US Preventive Services Task Force appears to be a positive for the potential uptake and insurance reimbursement of Exact Sciences' Cologuard multitarget stool DNA test.

However, the new statement, along with several accompanying evidence reports and commentaries — all published ahead of schedule today in the Journal of the American Medical Association after an embargoed copy of the report was leaked on Tuesday — also appear to be a mixed bag for the uptake of molecular CRC screening tests in general, as the task force stopped short of recommending their use over a variety of well-established non-molecular testing methods.

In formulating its recommendations, the USPSTF reviewed the evidence on the effectiveness of screening with colonoscopy, flexible sigmoidoscopy, computed tomography colonography, the guaiac-based fecal occult blood test, the fecal immunochemical test, Cologuard, and Epigenomics' methylated septin 9 gene DNA test to reduce the incidence of and mortality from colorectal cancer.

The task force also reviewed the potential harms of these tests, and their performance characteristics for detecting adenomatous polyps, advanced adenomas based on size, or both, as well as colorectal cancer.

The USPSTF concluded "with high certainty that screening for colorectal cancer in average-risk, asymptomatic adults aged 50 to 75 years is of substantial net benefit. Multiple screening strategies are available to choose from, with different levels of evidence to support their effectiveness, as well as unique advantages and limitations, although there are no empirical data to demonstrate that any of the reviewed strategies provide a greater net benefit."

In addition, the task force noted that "screening for colorectal cancer is a substantially underused preventive health strategy" in the US, and recommended screening for colorectal cancer starting at age 50 and continuing until age 75, a so-called "A" recommendation.

A draft version of the recommendation statement was made available for public comment in October. Of note, the draft recommendation language classified Exact's Cologuard as an "alternative" testing method, the ambiguity of which was largely viewed as a negative for the company as it would have likely affected insurance reimbursement of the test.

In the recommendation published today, the USPSTF noted that many comments on the draft statement expressed concern that the terms "recommended" and "alternative" to describe the testing strategies lacked clarity.

"In response, the USPSTF removed these terms from the final recommendation to better communicate the primary message of importance: there is convincing evidence that screening for colorectal cancer provides substantial benefit for adults aged 50 to 75 years, and a sizable proportion of the eligible US population is not taking advantage of this effective preventive health strategy," the new recommendation states. "With this recommendation, the USPSTF acknowledges that there is no 'one-size-fits-all' approach to colorectal cancer screening and seeks to provide clinicians and patients with the best possible evidence about the various screening methods to enable informed, individual decision making."

On Tuesday, the day of the apparent JAMA embargo break, Exact's stock skyrocketed 33 percent, from an opening price of $7.04 to a closing price of $9.39, in trading on Nasdaq. In afternoon trading on Wednesday the company's stock dropped a fraction of a percent to $9.33.

In a statement issued by Exact on Wednesday afternoon following the early JAMA publications, CEO and Chairman Kevin Conroy noted that the company "believes the final recommendations provide an important level of clarity to patients, physicians, and insurers, and that Cologuard should receive the benefits given to A-rated preventive services under the Affordable Care Act."

He added that the company is "pleased with the clarity of these recommendations and expect they will expand and promote utilization of Cologuard as an innovative colon cancer screening option."

Exact also noted that the final recommendations also recognize the use of Cologuard every three years, in line with the recommendation of the American Cancer Society and the coverage interval established by the Centers for Medicare and Medicaid Services.

Analysts generally greeted the news as a net positive for Cologuard, but exercised cautious optimism. Investment bank William Blair maintained an outperform rating on the company's stock, as analyst Brian Weinstein remarked in a research note that the updated recommendation "represents a significant clarification on the issue that caused Exact Sciences stock to fall dramatically last October."

"Said very clearly, this clarification places Cologuard on par with other screening strategies and makes it an 'A' rated test for individuals age 50-75," Weinstein added. "We expect this will have material impact on reimbursement discussions as the Affordable Care Act requires all 'A' rated screening tests to be covered without co-pay. In addition, we believe this will place Cologuard into quality metrics like HEDIS and Star, which should also push insurance coverage across the goal line."

Meantime, Goldman Sachs maintained a Neutral rating on Exact's stock and made no changes to its estimates or price target.

"We believe if the USPSTF labeled Cologuard as a recommended screening method, private payers would be required to cover the test with no co-pay (per the ACA)," Goldman Sachs analyst Isaac Ro commented in a research note. "However, the agency has stated a lack of head-to-head studies makes it difficult to recommend specific screening methods and decisions should be made on an individual basis. Thus, we believe payers can use 'reasonable medical management techniques' to determine the coverage limitations (per the ACA's statute on guidelines that do not specify a method). We therefore believe payer adoption/coverage for Cologuard will progress at a more measured pace."

The new recommendations are less encouraging for Epigenomics, whose Epi proColon methylated SEPT9 DNA test was recently approved by the US Food and Drug Administration. "A single test characteristic study met the inclusion criteria for the systematic evidence review supporting this recommendation statement; it found the SEPT9 DNA test to have low sensitivity (48 percent) for detecting colorectal cancer," the task force stated in its report.

In an accompanying JAMA Viewpoint, Ravi Parikh of Brigham and Women's Hospital and Vinay Prasad of the Knight Cancer Institute at Oregon Health and Science University outlined many of the shortcomings in the evidence that supported Epi proColon's FDA approval.

"Importantly, no evidence has shown that this new assay improves disease-specific or overall mortality compared against no screening or against accepted screening methods," the authors wrote. "Sigmoidoscopy and FOBT [fecal occult blood test] have both demonstrated these benefits in randomized trials, while colonoscopy and FIT [fecal immunohistochemistry testing] have not. Yet practically, colonoscopy includes sigmoidoscopy, and the rationale for FIT is more closely analogous to FOBT. Thus, in both cases, extrapolation may be more reasonable than blood-based screening, an entirely novel method."

Parikh and Prasad further noted that while population-wide cancer screening may be valuable, "physicians and policy makers must be objective about the comparative efficacy of novel blood-based screening tests. As the experience with SEPT9 blood testing shows, blood-based testing must balance convenience against the risk of inadequate screening, underdiagnosis, and reluctance to pursue further testing. Allowing blood-based screening tests for colon cancer to have a lower standard than that of other screening tests risks prioritizing convenience over patient safety and healthcare value."