Colorectal cancer (CRC) is a significant health issue, necessitating effective screening strategies to reduce its mortality. Current screening methods, including fecal immunochemical tests (FIT) and colonoscopy procedures, are effective but have limitations such as cost, invasiveness, and patient compliance. Colonoscopy is the most common CRC screening and diagnostic test in the US. Alternatively, FIT is a non-invasive test that detects blood in the stool, which may be an early sign of cancer. Recently, blood-based screening tests have emerged as another less invasive option that is more convenient for early detection of CRC. “The field is very excited about using blood tests to improve cancer screening, but their effectiveness in extending life would take multiple decades to establish through randomized trials – more time than it will take to develop new versions of these tests. Our study strived to answer an intuitive question: how accurate and affordable would blood tests have to be so that they can replace FIT or colonoscopy?” Dr. Pedro Nascimento de Lima explained.
The study, published in the Journal of the National Cancer Institute, employed a microsimulation approach using three Cancer Intervention and Surveillance Modeling Network (CISNET) models. CISNET models are sophisticated computer simulations used to predict the impact of cancer control interventions, such as screening, on population health. The researchers analyzed four screening strategies: no screening (as a comparator), colonoscopy every 10 years, FIT every year, and a blood test every three years. Key parameters they considered in their analysis included test cost, sensitivity for CRC and advanced adenomas (AA, large growths in the colon that are more likely to turn into cancer), and screening interval. The researchers evaluated a total of 900 scenarios, incorporating different combinations of test accuracy, costs, and intervals.
The research identified several key findings on the effectiveness and cost-effectiveness of blood tests for detecting CRC. Without screening, the simulation predicted there would be 32-36 CRC deaths per 1,000 individuals, with an average lifetime cost of $5,268-5,845 per person for CRC care. When individuals underwent annual FIT testing, the number of CRC deaths significantly decreased to between 6 and 12 per 1,000 people. This screening method also led to a substantial increase in quality-adjusted life years (QALYs), providing an additional 125 to 163 years of good health per 1,000 people. Screening with a colonoscopy every 10 years was even more effective, reducing the number of CRC deaths to between 4 and 10 per 1,000 people. The cost per person for this method was higher, ranging from $5,375 to $7,031. The increase in quality-adjusted life years was also higher, with 132 to 177 extra years of good health per 1,000 people screened. When evaluating the blood test every three years, the number of CRC deaths was between 14 and 18 per 1,000 people. The average cost per person for this method was between $8,559 and $9,413. While this method was still better than no screening, it resulted in 34% to 50% fewer years of good health (QALYs) and 52% to 70% lower net monetary benefits compared to a colonoscopy every 10 years.
Dr. Nascimento de Lima emphasized, "All our models agreed that blood tests would need to be much more sensitive—4 to 5 times more sensitive—to advanced adenoma detection, detection of a precursor lesion to CRC, and a lot cheaper if they are to be cost-effective. Until then, anyone who uses these tests would be better off just sticking with stool tests or colonoscopies."
The study suggests that while blood-based screening tests can be cost-effective relative to no screening, their effectiveness and economic value are significantly lower than those of established methods like FIT and colonoscopy. Dr. Nascimento de Lima pointed out, "Blood tests will be better than nothing if you are not screened at all, but we need higher standards if we want to achieve the moonshot goal of reducing cancer incidence and also control health costs. Right now, the available blood tests for colorectal cancer screening are not the solution that will take us there because they are more expensive and less effective than anything else in the market."
Dr. Carolyn Rutter, a professor at Fred Hutch Cancer Center, also highlighted a potential issue. "There is concern that if blood tests are offered, their convenience would result in people shifting from more effective screening modalities to less effective and more costly blood tests." For blood tests to be competitive, they must demonstrate higher sensitivity for advanced adenomas and CRC development while also reducing costs or implement more frequent intervals of testing. "Our next analyses are looking at the impact of these shifts. We’re also starting work to estimate how the use of a blood test that detects multiple cancers might offset the loss of benefit from preventing colorectal cancer by detecting advanced adenomas," Dr. Rutter added.
The research was funded by grants from the National Cancer Institute and the National Institute of Health.
Fred Hutch/University of Washington/Seattle Children's Cancer Consortium member Dr. Carolyn Rutter contributed to this work.
Nascimento De Lima, P., Van Den Puttelaar, R., Knudsen, A. B., Hahn, A. I., Kuntz, K. M., Ozik, J., Collier, N., Alarid-Escudero, F., Zauber, A. G., Inadomi, J. M., Lansdorp-Vogelaar, I., & Rutter, C. M. 2024. Characteristics of a cost-effective blood test for colorectal cancer screening. Journal of the National Cancer Institute, djae124. Advance online publication.
| Science Spotlight writer Darya Moosavi is a postdoctoral research fellow within Johanna Lampe's research group at Fred Hutch. Darya studies the nuanced connections between diet, gut epithelium, and gut microbiome in relation to colorectal cancer using high-dimensional approaches. |