Non-invasive blood test shows 83% sensitivity in detecting colorectal cancer, offering hope for early diagnosis

By Dr. Chinta SidharthanReviewed by Lily Ramsey, LLMMar 18 2024

In a recent study published in The New England Journal of Medicine, a team of scientists from the United States (U.S.) and Canada evaluated the performance of a blood-based testing method that uses cell-free deoxyribonucleic acid (DNA) to screen for colorectal cancer.

Study: A Cell-free DNA Blood-Based Test for Colorectal Cancer Screening. Image Credit: Connect world/Shutterstock.com

Background

Colorectal cancer is one of the most prevalent forms of cancer among the adult population of the United States, with the second-highest mortality rate and the third-highest incidence rate.

Although the lifetime risk of the disease is 4%, the overall survival is dependent on early detection of the cancer.

Individuals in whom the cancer is detected early, in the localized stages, have a 91% five-year survival rate, while those in whom the cancer has moved to the metastatic stage have a 14% five-year survival rate.

Leading cancer experts, as well as bodies such as the U.S. Preventive Services Task Force, recommend asymptomatic screening to decrease the incidence and mortality associated with colorectal cancer.

However, despite the various stool-based and direct visualization tests available for colorectal cancer screening, the adherence rate for regular asymptomatic screening is 59%.

Furthermore, a significant percentage of colorectal cancer-related mortality is among individuals who are not regular with screening. These statistics highlight the need for an easily administered method for colorectal cancer screening to increase screening adherence.

About the study

In the present study, the scientists evaluated the performance of a blood-based test that screens for colorectal cancer using cell-free DNA.

They aimed to address the major factors responsible for the low adherence rates for colorectal cancer screening, which include pain and invasiveness of the testing methods, the time required to administer the test, the embarrassment and discomfort associated with endoscopy, and the lack of proximity to test provider, among others.

A multicenter, observational, prospective study enrolled eligible individuals across over 200 sites, including endoscopy and primary care centers.

Individuals between the ages of 45 and 84 years were eligible to participate in the study if they routinely underwent colonoscopy-based screening and were at average colorectal cancer risk.

Individuals with inflammatory bowel disease, a genetic predisposition to or family history of colorectal cancer, or any history of cancer were excluded from the study.

All participants provided a blood sample before they underwent colonoscopy. A colonoscopy that included visualization and photographic documentation of the ileocecal valve or appendiceal orifice was considered complete unless the visualization was prevented due to a large mass or lesion.

The location and size of lesions identified through colonoscopy were noted, and those resected were further processed for histopathological analyses.

The blood samples were subjected to cell-free DNA assays to detect genomic alterations, genetic fragmentation, and aberrant methylation patterns in the cell-free DNA that indicate colorectal cancer.

The two primary outcomes of the study were the sensitivity and specificity for colorectal cancer and advanced neoplasia, respectively. The test's sensitivity in detecting advanced precancerous lesions was the secondary outcome.

Results

The results showed that the blood-based test using cell-free DNA had a sensitivity of 83% in detecting colorectal cancer, a specificity of 90% in the detection of advanced neoplasia, and only a 13% sensitivity in detecting advanced precancerous lesions. The test also had a 10% false positive rate in detecting neoplasia.

Despite the highly diverse study population with regard to race and ethnicity, the performance of the test did not show any significant variation, indicating that it performed uniformly across all subgroups. However, age was a factor that affected the test's specificity conversely, possibly due to cell-free DNA methylation signals that were age-specific.

The colorectal cancer detection sensitivity of this blood-based cell-free DNA test was higher than that of the fecal immunohistochemical test (67.3%) but lower than that of the multitarget stool DNA test (93.9%).

However, the sensitivity of the blood-based test in detecting advanced precancerous lesions was the lowest in comparison to tests such as the methylated Septin9 test, fecal immunohistochemical test, and multitarget stool DNA test.

Furthermore, the test's sensitivity also differed based on the clinical stage of colorectal cancer, with a 55% sensitivity for stage I cancer and an 81% sensitivity for colorectal cancer in stages I to III.

Conclusions

To summarize, the study found that a blood-based test using cell-free DNA to detect colorectal cancer had a sensitivity of 83% in detecting colorectal cancer, which was higher than that of stool-based immunohistochemical tests but lower than that of stool-based DNA tests.

However, the sensitivity of the test in detecting advanced precancerous lesions was lower than that of any other method.

Although the blood-based test provides a fast, relatively painless, and non-invasive method for screening for colorectal cancer, these results indicate that further research among wider study populations is required to improve the sensitivity and specificity of the test.