A new blood test doesn’t change the game for colorectal cancer screening
Colorectal cancer (CRC) stands as the second leading cause of cancer-related deaths in the United States, with nearly 53,000 deaths reported in 2022. While the high mortality rate is concerning, a significant proportion of these deaths could have been prevented with timely screenings. It is estimated that 68% of CRC deaths occur in individuals who either failed to undergo screenings at appropriate intervals or never participated in screening programs at all. The importance of early CRC detection cannot be overstated, as early intervention can drastically improve survival rates.
However, despite the availability of screening methods such as colonoscopies, a significant barrier to widespread screening is the procedure’s complexity and cost. Colonoscopies require specialized equipment, skilled professionals, and a preparation process that many individuals find cumbersome. As a potential alternative, a new blood-based CRC screening test has been developed and evaluated. This test aims to provide a more accessible method for detecting CRC, offering a potential solution for those who may hesitate to undergo traditional screening methods.
How the Blood-Based CRC Test Works
The newly developed blood-based test for CRC relies on cell-free DNA (cfDNA) found in the bloodstream. When cells, including tumor cells, die, small fragments of DNA are released into the surrounding tissues and eventually enter circulation. The blood test uses cfDNA to detect CRC by assessing two key components: the fraction of tumor-derived cfDNA and a composite score that evaluates common CRC somatic mutations, aberrant methylation patterns, and fragmentation profiles.
The test’s accuracy was determined through a training set of over 4,000 blood samples from both healthy individuals and CRC patients. Using this data, algorithms were created to predict CRC presence based on the identified biomarkers. A positive result occurs when either of the two scores exceeds specific thresholds established by the algorithm. This innovative approach to CRC screening aims to provide a non-invasive, easy-to-administer option for individuals who are at average risk for CRC.
Study Design and Findings
The study evaluating the blood-based test involved 7,861 participants aged 45-84 who were undergoing routine colonoscopies for CRC screening. The participants provided blood samples ideally within 60 days prior to their colonoscopy. The study found that 65 participants were diagnosed with CRC, 1,116 had advanced precancerous lesions, 2,166 had non-advanced adenomas, and 4,514 had negative colonoscopy results.
The blood test demonstrated an impressive sensitivity of 83.1% for detecting CRC (95% CI: 72.2-90.3), correctly identifying 54 out of the 65 CRC cases. The test was particularly effective in detecting cancers at later stages, including Stage II, III, and IV cancers. However, the test missed six of the 17 Stage I cancers, as well as five of the seven cancers without complete staging. This indicates that the test is less effective in detecting early-stage cancers, especially those with smaller lesions under 9 mm.
For advanced precancerous lesions, the test had a much lower sensitivity of 13.2%, identifying only 147 out of the 1,116 cases. While this reflects the test's limited ability to detect early-stage precancerous lesions, its ability to detect CRC at later stages is notable. Additionally, the specificity of the test was 89.6%, meaning it correctly identified participants without CRC in most cases. However, specificity decreased with age, likely due to an increase in methylation that can result in false positives in older individuals.
Comparison to Other Non-Invasive CRC Tests
The cfDNA test's performance was compared to other non-invasive CRC screening tests, including stool-based tests and imaging methods like CT colonography. While the cfDNA test holds promise due to its convenience and non-invasive nature, its performance is not exceptional when compared to existing tests. For instance, stool-based tests like DNA-FIT (also known as Cologuard) have a higher sensitivity for detecting early-stage cancers and advanced precancerous lesions. DNA-FIT tests outperform the cfDNA test in detecting Stage I cancers, where the highest chances of survival lie.
CT-colonography, though more intensive and requiring bowel preparation similar to colonoscopies, is effective at detecting smaller lesions that the cfDNA test misses. The cfDNA test is also outperformed by DNA-FIT tests in terms of detecting advanced precancerous lesions. Despite its limitations, the cfDNA test provides a convenient option for patients who might otherwise avoid colonoscopies or stool-based tests.
The Superiority of Colonoscopy
While the cfDNA test is a promising advancement, colonoscopy remains the gold standard for CRC screening. Colonoscopy not only detects cancer but can also be used to remove precancerous lesions during the procedure, preventing the development of CRC. Unlike non-invasive tests, colonoscopy allows direct visualization of the colon, making it a more comprehensive screening method. However, non-invasive tests like cfDNA could serve as a complementary option to reach individuals who are hesitant to undergo colonoscopies.
The Bottom Line
The ideal cancer screening test would offer both high sensitivity and specificity, allowing for early detection while minimizing false positives. While the new cfDNA test is a step forward in non-invasive CRC screening, its performance is not yet superior to other established tests, particularly in detecting early-stage cancers and advanced precancerous lesions. Its high specificity and convenience make it an attractive option, but the low sensitivity for early-stage cancer detection means that it cannot replace colonoscopies or more sensitive stool-based tests. For now, while the cfDNA test may serve as an additional tool for CRC screening, follow-up with traditional methods like colonoscopy remains essential for comprehensive cancer detection and prevention.
Update from Peter Attia, on 2024-08-31Source