Colonoscopy and stool tests more effective and cost-effective than novel blood-based screening tests

Abstract

Novel first-generation blood-based tests for colorectal cancer screening may decrease the incidence and mortality of colorectal cancer in comparison with no screening but are far less effective and cost-effective than colonoscopy and the currently available stool tests, according to a cost-effectiveness analysis comparing colorectal screening options that has been published in the Annals of Internal Medicine.¹

The study was conducted to estimate the clinical and economic impacts of cutting-edge colorectal screening tests, or first-generation cell-free DNA blood tests, in comparison with colonoscopy and stool tests such as fecal immunochemical testing (FIT) and multitarget stool DNA testing (MT-sDNA or Cologuard). The novel tests that were assessed included those recently approved by the US Food and Drug Administration as well as a blood test that detects circulating DNA that may arise from cancers (Guardant Shield), a novel FIT-RNA test (Geneoscopy ColoSense), and a next-generation FIT-DNA blood test.

“Even though it is a scientific breakthrough to be able to detect signals in the blood from colorectal cancer, the detection rate for early-stage cancers and for precancerous polyps is not high with the first generation of blood tests,” says the lead author of the study, Uri Ladabaum, MD, professor of medicine and director of the Gastrointestinal Cancer Prevention Program at Stanford University School of Medicine. “That is what makes their expected benefit lower than with stool tests or colonoscopy, which lead to more prevention via removal of precancerous polyps and early detection of cancer.”

For example, the study found that colonoscopy and FIT yielded more than a 70% reduction in the number of colorectal cancers and more than a 75% reduction in colorectal cancer deaths in comparison with no screening (assuming a 100% participation in screening), whereas the reductions in the number of colorectal cancers and deaths with the novel blood-based test Guardant Shield were 42% and 56%, respectively.

Colonoscopy and stool tests also were less costly. For example, the MT-sDNA stool test (Cologuard) cost $6300 per quality-adjusted life-year (QALY) gained versus no screening compared to $89,600 per QALY gained with the Guardant Shield versus no screening.

Investigators used computerized modeling based on all available information on current and novel blood-based screening tests to make projections about the number of colorectal cancer cases and deaths that could be expected with various screening strategies over time.

Dr Ladabaum says that a key motivation for conducting the analysis was to assess what might happen if blood-based tests increase screening and if they are used instead of colonoscopy or stool-based tests.

To address these questions, he and his colleagues played out several plausible scenarios to provide long-term outcome estimates of colorectal cancer incidence and deaths based on the implementation of the various screening options.

For example, they looked at the effectiveness of blood-based testing (Guardant Shield) when followed by colonoscopy in patients with an abnormal test. They found that the effectiveness of the blood-based screening test eroded substantially as the follow-up rate with colonoscopy decreased.

Dr Ladabaum says that the findings indicate that colonoscopy and stool tests should remain the preferred screening approaches for colorectal cancer screening. “At this time, blood tests should not replace stool tests or colonoscopy,” he says. “If you are willing and able to do stool-based testing or screening colonoscopy, at present, that will optimize your chances of protection against getting colorectal cancer or dying from it.”

Current data do not support blood-based testing between colonoscopies either, he says, referring to so-called hybrid screening programs. “This is a future research question, and the answer will depend on the balance between finding previously missed cancers or high-risk polyps at a treatable stage versus generating false positives that will lead to unnecessary worry and testing that can cause harm.”

Although he says that current blood tests are not preferred for any population, they are a good option for people who absolutely cannot or will not undergo stool testing or screening colonoscopy.

In the future, he says, blood-based tests may one day challenge the role of screening colonoscopy and stool-based testing, but only if they become affordable and are able to detect stage I cancer and advanced precancerous polyps with a high degree of sensitivity. He calls this a big “if.”

Commenting on the study, Virginia Shaffer, MD, professor of surgery and chief of the Section of Colon and Rectal Surgery at the University of Chicago, says that the study provides important information highlighting that although novel blood-based screening testing is better than nothing, it is not better than colonoscopy.

“If a patient is willing and able to get a colonoscopy, this should remain the top choice,” she says.

She underscores that the novel blood-based tests should not “replace” colonoscopy and says that they are helpful only “if they ideally reach people who otherwise would not have gotten a colonoscopy.” She also notes that people need to understand that the test should be performed repeatedly, as performing it only once is not clinically effective or cost-effective.

Although the blood tests are helpful for reaching a wider patient population, Dr Shaffer says that “one fear is that people who otherwise would have gotten a colonoscopy decide not to have one because the test is ‘easier.’”