Because colonoscopies and more established stool-based tests are more effective at detecting early cancers and precancerous polyps compared with emerging blood-based tests, their long-term impact is projected to be substantially greater than that of blood-based tests, according to a recent study published by Ladabaum et al in the Annals of Internal Medicine. The findings revealed that despite the newly available blood-based tests being ideal for patients who would otherwise forgo other colorectal cancer screening, if too many patients who would have undergone colonoscopies or stool-based tests switch to these blood tests, colorectal cancer mortality rates could rise.
Background
With the current screening rates in the population, about 4% of all U.S. adults will be diagnosed with colorectal cancer during their lifetimes. Regular screening can help identify early cancers and precancerous polyps as well as reduce a patient’s risk of developing and dying from colorectal cancer. The U.S. Preventive Services Task Force currently recommends that all adults between the ages of 45 and 75 years undergo screening for colorectal cancer.
For decades, screening has required either a once-per-decade colonoscopy or a stool-based test every 1 to 3 years. During a colonoscopy, physicians can not only detect colorectal cancers, but also remove precancerous polyps that can develop into cancers.
“This makes colonoscopy a unique cancer screening method because you also have the possibility of cancer prevention,” emphasized lead study author Uri Ladabaum, MD, Professor of Gastroenterology at Stanford Medicine. “Despite that, there are many [patients] who are not getting screened at all, or who are not getting screened as often as they should,” he indicated.
Data show that about 33% of U.S. adults in the recommended age range have never undergone screening for colorectal cancer. As a result, physicians are hoping that new methods could encourage them to undergo screening.
In 2014, the U.S. Food and Drug Administration (FDA) approved the first multitarget stool-based colorectal screening test, in which stool collected at home by a patient every 1 to 3 years is analyzed for the presence of small amounts of blood or cancer DNA. In the summer of 2024, the FDA approved a novel colorectal cancer screening strategy that detects small amounts of cancer DNA circulating in a patient’s bloodstream. Although blood-based tests can sound more appealing than a standard, invasive colonoscopy, these first-generation blood-based tests do not diagnose precancerous polyps well.
“The first generation of blood-[based] tests are a really exciting development in the colorectal cancer screening paradigm. [However], for now, if [patients are] willing and able to do a colonoscopy or stool-based test, [they shouldn’t] switch to a blood-[based] test,” cautioned Dr. Ladabaum. “This is a time of intense interest in the colorectal cancer screening field. The paradigm in screening could be changing, [b]ut 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,” he suggested.
Study Methods and Results
In the recent study, investigators used previously published data on six commercially available or in-development blood- and stool-based screening tests as well as the standard colonoscopy to model the relative rate of colorectal cancer and deaths among 100,000 average-risk patients who used each screening approach.
The investigators found that among 100,000 patients who underwent a colonoscopy every 10 years, 1,543 would develop colorectal cancer and 672 would die from the disease. For stool-based tests taken every 1 to 3 years, the incidence of colorectal cancer ranged from 2,181 to 2,498 cases per 100,000 patients, and deaths ranged from 904 to 1,025. For the new blood-based tests, recommended to be conducted every 3 years, the cases ranged from 4,310 to 4,365, and deaths ranged from 1,604 to 1,679—a rate that was about 2.5 times higher compared with the colonoscopy group. Among those who received no screening, 7,470 would develop colorectal cancer and 3,624 would die from the disease.
In addition, when the investigators examined the costs associated with each test, they found that colonoscopies and stool-based tests were more cost-effective compared with the blood-based tests.
The investigators noted that at a population level, blood-based tests will be effective at reducing colorectal cancer mortality rates only if patients who reliably take the tests every 3 years subsequently agree to receive a follow-up colonoscopy if they return positive results.
“The blood tests are certainly much better than nothing, but you’ll worsen the population outcomes and raise health-care costs if you see [patients] switching from colonoscopies to first-generation blood tests,” Dr. Ladabaum stated.
After modeling the effect of patient choices on population-wide colorectal cancer rates, they found most patients continuing to screen with colonoscopy or stool-based tests as the best-case scenario. The investigators underlined that blood-based tests should be used only by patients who would not otherwise undergo screening.
Conclusions
“It remains to be seen who will really use the blood-[based] tests. Will it be [patients] who have never been screened using any other method, [a]nd will they be willing to get a follow-up colonoscopy if indicated?” said Dr. Ladabaum.
Further studies may require real-world data on patient choices regarding colorectal cancer screening to better refine the model on how the blood-based tests will affect colorectal cancer incidence and mortality rates.
The investigators noted that if blood-based tests were to improve, the current results would not hold true for future generations of the tests. Nonetheless, they hope that patients and physicians continue to use the most effective screening methods currently available.
“Ideally, we want as many [patients] 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,” Dr. Ladabaum concluded.
Disclosure: The research in this study was funded by the Gorrindo Family Fund. For full disclosures of the study authors, visit acpjournals.org.
