A new study published in the Annals of Internal Medicine comparing traditional and emerging screening tests for colorectal cancer (CRC) showed that first-generation cell-free blood DNA (cf-bDNA) tests could significantly reduce CRC incidence and mortality compared to no screening. However, their impact is considerably lower than that of colonoscopy or stool-based tests.
The study examined the potential impact of four new noninvasive CRC screening tests compared to traditional methods such as colonoscopy, fecal immunochemical tests (FIT), and multitarget stool DNA (mt-sDNA) tests. The four emerging tests included two cell-free blood DNA (cf-bDNA) tests (Guardant Shield and Freenome), an enhanced next-generation mt-sDNA stool test, and the ColoSense FIT-RNA fecal test.
Unlike established methods, the cf-bDNA tests are blood-based and less invasive, making them more accessible for people who may avoid traditional colonoscopy or stool tests. The study utilized the Model of Screening and Surveillance for Colorectal Cancer (MOSAIC) to estimate the long-term impact on CRC incidence and mortality.
Effectiveness of new screening tests
The findings indicate that both traditional and emerging screening methods significantly reduce CRC incidence and mortality. Assuming 100% adherence to screening and follow-up, colonoscopy and FIT reduce CRC incidence by over 70% and mortality by 75%, compared to no screening. The mt-sDNA test offers reductions of 68% and 73%, respectively. Enhanced mt-sDNA and FIT-RNA tests perform similarly to the traditional mt-sDNA test, with slightly lower reductions. The cf-bDNA tests, while still beneficial, show a lesser impact: reducing CRC incidence by 42% and mortality by 56% compared to no screening.
While the blood tests are less invasive and potentially more appealing to those avoiding other options, they provide a smaller reduction in CRC mortality and incidence. This may be partly due to the fact that the sensitivity of cf-bDNA tests for early-stage CRC remains modest.
The authors concluded that, under ideal conditions, substituting cf-bDNA tests for traditional methods like FIT or colonoscopy could lead to worse population-level outcomes. However, they suggest that cf-bDNA screening becomes potentially beneficial when used in populations who are unwilling or unable to undergo colonoscopy or stool-based tests, especially when there is a high rate of follow-up colonoscopy after abnormal results.
Role of adherence in screening outcomes
Participation across the screening continuum is crucial to maximizing the benefits of CRC screening. The researchers cite that real-world adherence to follow-up colonoscopy after an abnormal screen remains low—only 51.4% within 180 days in some U.S. healthcare settings, according to recent studies. Since poor follow-up severely undermines the effectiveness of both stool- and blood-based screening methods, the authors emphasize that improving adherence to follow-up colonoscopy could amplify the benefits of all screening methods.
This analysis sheds light on the nuanced decision-making required when integrating new CRC screening options into clinical settings. Although cf-bDNA tests offer the appeal of a blood-based, non-invasive method, the authors conclude that they should be carefully positioned to reach individuals who otherwise would not participate in CRC screening.
