Weighing screening options for colorectal cancer in a changing landscape

Newly available blood tests to screen for colorectal cancer sound far more appealing than a standard colonoscopy. Instead of clearing your bowels and undergoing an invasive procedure, the tests require only a simple blood draw. But are the tests effective?

A study led by researchers at Stanford Medicine concluded that the new tests are ideal for people who shy away from other colorectal cancer screening. However, if too many people who would have undergone colonoscopies or stool-based tests switch to the blood tests, colorectal cancer death rates will rise. Because the more established colonoscopies and stool tests are more effective at detecting early cancers and precancerous polyps than the emerging blood tests, their long-term impact is projected to be substantially greater than that of blood tests, the researchers found.

"The first generation of blood tests are a really exciting development in the colorectal cancer screening paradigm," said Uri Ladabaum, MD, a professor of gastroenterology and the first author of the paper, to be published Oct. 28 in Annals of Internal Medicine. "But for now, if you're willing and able to do a colonoscopy or stool-based test, don't switch to a blood test."

Ladabaum also pointed out that, at a population level, the blood tests will be effective at reducing colorectal cancer deaths only if people who reliably take the test every three years subsequently agree to receive a follow-up colonoscopy if the blood test returns a positive result.

Weighing the options

With the current screening rates in the population, about 4% of all American adults will be diagnosed with colorectal cancer at some point in their lifetimes. Regular screening can help identify early cancers and precancerous polyps and reduce a person's risk of developing, and dying, from colorectal cancer. The U.S. Preventive Services Task Force recommends that all adults between the ages of 45 and 75 be screened for colorectal cancer.

For decades, screening has required either a once-a-decade colonoscopy, in which a thin flexible tube with a camera is used to look inside a person's large intestine, or a stool test every one to three years. During a colonoscopy, clinicians can not only detect colorectal cancers, but also remove precancerous polyps which can develop into cancers.

This makes colonoscopy a unique cancer screening method because you also have the possibility of cancer prevention. Despite that, there are many people who are not getting screened at all, or who are not getting screened as often as they should."

Uri Ladabaum, MD, professor of gastroenterology and first author of the paper

Data show that about 1 in 3 American adults in the recommended age range have never been screened for colorectal cancer, so clinicians are hoping that new methods could encourage them to undergo screening.

In 2014, the U.S. Food and Drug Administration approved the first multi-target stool-based colorectal screening test, in which stool collected at home by a patient every one to three years is analyzed for the presence of small amounts of blood or cancer DNA. This summer, the FDA approved a new method that looks for bits of cancer DNA circulating in a person's bloodstream. These first-generation blood-based tests do not diagnose precancerous polyps well.

"This is a time of intense interest in the colorectal cancer screening field. The paradigm in screening could be changing," Ladabaum said. "But conducting a randomized controlled trial directly comparing these emerging screening tests over the long term is unfeasible, which leaves patients in a difficult place when they're weighing their options."

Comparing effectiveness

Ladabaum and his collaborators collected previously published data on six commercially available or in-development blood- and stool-based screening tests as well as the gold-standard colonoscopy. Using this data, they modeled the relative rate of colorectal cancer and deaths among 100,000 average-risk people who used each screening approach.

Among 100,000 people who receive a colonoscopy every 10 years, 1,543 would develop colorectal cancer and 672 would die from the disease, they determined. For stool-based tests every one to three years (depending on test) the incidence of colorectal cancer ranged from 2,181 to 2,498 cases per 100,000 people, and deaths ranged from 904 to 1,025. For the new blood tests, recommended to be conducted every three years, the cases ranged from 4,310 to 4,365, and deaths ranged from 1,604 to 1,679 -; about two and a half times as many deaths as in the colonoscopy group.

Among those who receive no screening, 7,470 would develop the cancer, and 3,624 would die from it.

Moreover, when the group looked at the costs associated with each test, they found that colonoscopies and stool-based tests were more cost-effective than the blood-based tests.

"The blood tests are certainly much better than nothing, but you'll worsen the population outcomes and raise health care costs if you see people switching from colonoscopies to first-generation blood tests," Ladabaum said.

Modeling patient choices

When Ladabaum's group modeled the effect of patient choices on population-wide colorectal cancer rates, they found most people continuing to screen with colonoscopy or stool-based tests as the best-case scenario. Blood tests should be used only by people who would not otherwise be screened.

The research team said they need real-world data on patient choices about colorectal cancer screening to better refine their model on how the blood tests will affect cancer rates.

"It remains to be seen who will really use the blood tests," Ladabaum said. "Will it be people who have never been screened using any other method? And will they be willing to get a follow-up colonoscopy if indicated?"

He also said blood tests could improve, and the current results would then not hold true for future generations of the tests.

For now, the researchers hope that patients -; and clinicians -; stick with the most effective screening methods currently available. 

"Ideally, we want as many people as possible to get screened for colorectal cancer, and that's likely going to mean a combination of different tests being used across the population," Ladabaum said.

Scientists from the University of Pittsburgh, the University of Washington, and the Oregon Health and Sciences University contributed to the research.

Funding for this research was provided by the Gorrindo Family Fund.