Next-Generation Stool-Based Tests Show Promise for Improved Colorectal Cancer Screening

Core Concepts

Multitarget stool-based tests, including DNA, RNA, and protein-based approaches, demonstrate improved sensitivity for detecting colorectal cancer and advanced precancerous lesions compared to the current standard fecal immunochemical test (FIT), but may also have lower specificity leading to more false-positive results.

Abstract

The article discusses the development and potential of three new multitarget stool-based tests for colorectal cancer (CRC) screening in average-risk individuals. These tests aim to improve upon the current standard fecal immunochemical test (FIT) by detecting additional biomarkers associated with CRC.
The first test, Cologuard 2.0, is an updated version of the existing Cologuard DNA-based test. It detects three novel methylated DNA markers along with fecal hemoglobin. In a recent trial, Cologuard 2.0 demonstrated better sensitivity for CRC (93.9% vs 67.3%) and advanced precancerous lesions (43.4% vs 23.3%) compared to standard FIT, but had lower specificity (90.6% vs 94.8%).
The second test, ColoSense, is an RNA-based stool test that looks for eight RNA biomarkers associated with CRC. In the CRC-PREVENT trial, ColoSense showed higher sensitivity than standard FIT for CRC (94% vs 78%) and advanced adenomas (46% vs 29%), but was less specific (88% vs 96%).
The third test is a multitarget protein-based FIT that uses antibodies to detect two additional proteins: calprotectin and serpin family F member 2. A 2021 study found its sensitivity for advanced neoplasias was 42.9% compared to 37.3% with standard FIT, with similar specificity.
The article also discusses a modeling study that compared the multitarget protein-based test to standard FIT. When both tests were set at the same low positivity threshold, the multitarget test identified slightly more advanced lesions while resulting in fewer false-positives.
Overall, these new multitarget stool-based tests show promise for improving the early detection of CRC and advanced precancerous lesions, but the trade-off may be an increased likelihood of false-positive results compared to standard FIT. Successful implementation would also depend on patient adherence to follow-up colonoscopy after a positive test.

Stats

Cologuard 2.0 sensitivity for CRC: 93.9%
Cologuard 2.0 sensitivity for advanced precancerous lesions: 43.4%
Standard FIT sensitivity for CRC: 67.3%
Standard FIT sensitivity for advanced precancerous lesions: 23.3%
Cologuard 2.0 specificity: 90.6%
Standard FIT specificity: 94.8%
ColoSense sensitivity for CRC: 94%
ColoSense sensitivity for advanced adenomas: 46%
Standard FIT sensitivity for CRC: 78%
Standard FIT sensitivity for advanced adenomas: 29%
ColoSense specificity: 88%
Standard FIT specificity: 96%
Multitarget protein-based test sensitivity for advanced neoplasias: 42.9%
Standard FIT sensitivity for advanced neoplasias: 37.3%
Multitarget protein-based test specificity for advanced neoplasias: 96.6%
Standard FIT specificity for advanced neoplasias: 96.6%

Quotes

"Cologuard 2.0 demonstrated better sensitivity for CRC than did standard FIT (93.9% vs 67.3%, respectively) and for advanced precancerous lesions (43.4% vs 23.3%)."
"ColoSense showed higher sensitivity than standard FIT for the presence of CRC (94% vs 78%, respectively) and advanced adenomas (46% vs 29%)."
"In scenario 2, with both tests set at the same low positivity threshold to minimize false-positives, the protein-based test resulted in fewer false-positives than did the standard test (295 vs 311, respectively), resulting in a slightly higher specificity."

Key Insights Distilled From

What to Know About the Next-Gen FIT for CRC Screening

by M. Alexander... at www.medscape.com 04-11-2024

https://www.medscape.com/viewarticle/what-know-about-next-gen-fit-crc-screening-2024a10006yo

Deeper Inquiries

How do the cost-effectiveness and patient adherence rates compare between the multitarget stool-based tests and standard FIT for colorectal cancer screening?

The cost-effectiveness of multitarget stool-based tests compared to standard FIT for colorectal cancer screening can vary. While the standard FIT is generally more cost-effective, with a lower cost per test (around $30), multitarget stool-based tests like Cologuard 2.0 and ColoSense are more expensive (over $600 per test). This higher cost can be a limiting factor for widespread adoption and implementation of these newer tests.
In terms of patient adherence rates, there may be differences between the tests. The increased sensitivity of multitarget stool-based tests may lead to higher patient adherence rates as individuals may feel more confident in the accuracy of the test results. However, the higher cost of these tests could potentially deter some patients from undergoing screening, impacting adherence rates. Patient education and awareness campaigns may be necessary to address these barriers and improve adherence rates for multitarget stool-based tests.

What are the potential limitations or drawbacks of relying solely on stool-based tests, even with improved sensitivity, for colorectal cancer screening compared to colonoscopy?

While multitarget stool-based tests offer improved sensitivity for detecting colorectal cancer and advanced precancerous lesions compared to standard FIT, there are still limitations and drawbacks to relying solely on stool-based tests for colorectal cancer screening. One major limitation is the potential for false-positive results, which can lead to unnecessary follow-up procedures and anxiety for patients. Additionally, stool-based tests may not be able to detect all types of colorectal abnormalities, such as flat or serrated lesions, which could be missed without a colonoscopy.
Another drawback is the lack of therapeutic capabilities with stool-based tests. If abnormalities are detected, patients will still need to undergo a colonoscopy for further evaluation and potential treatment. This can result in delays in diagnosis and treatment, especially if patients are hesitant to follow through with a colonoscopy after receiving a positive stool-based test result. Colonoscopy remains the gold standard for colorectal cancer screening as it allows for direct visualization and removal of precancerous lesions during the same procedure.

What other emerging technologies or approaches are being explored to further enhance colorectal cancer detection and prevention beyond the stool-based tests discussed in this article?

Beyond the multitarget stool-based tests discussed in the article, there are several emerging technologies and approaches being explored to enhance colorectal cancer detection and prevention. One promising approach is the development of blood-based biomarker tests that can detect circulating tumor DNA or other markers in the blood, offering a non-invasive alternative to stool-based tests. These blood tests, often referred to as liquid biopsies, have the potential to improve early detection of colorectal cancer and monitor treatment response.
Another emerging technology is the use of artificial intelligence (AI) and machine learning algorithms to analyze imaging data from colonoscopies and other diagnostic tests. AI can help identify subtle abnormalities that may be missed by human observers, improving the accuracy of colorectal cancer screening and reducing the risk of false-negative results.
Furthermore, research is ongoing in the field of microbiome analysis, studying the gut microbiota's role in colorectal cancer development. By understanding the interactions between gut bacteria and colorectal cancer, researchers hope to develop microbiome-based screening tests that can complement existing screening methods and provide additional insights into an individual's risk of developing colorectal cancer. These innovative approaches hold promise for advancing colorectal cancer detection and prevention beyond traditional screening methods.