Can a Multitarget Stool RNA Test Detect Colorectal Cancer?

In a prospective, cross-sectional clinical trial, researchers found that a multitarget stool RNA test could be highly effective as a noninvasive screening tool for colorectal cancer.

Screening for colorectal cancer can lower mortality and prevent colorectal cancer development by helping patients detect early-stage disease or precancerous lesions. The US Preventive Services Task Force (USPSTF) recommends invasive and noninvasive screening options, and though colonoscopies are the criterion standard for screenings, adherence rates are consistently low at approximately 60%.

To encourage hesitant patients to be screened by a noninvasive alternative, the researchers sought to determine if a mt-sRNA test could effectively detect colorectal cancer. The phase 3 clinical trial was a blinded, prospective, cross-sectional study, which included 8920 participants, identified through social media and enrolled between June 2021 to June 2022. Participants provided stool samples and completed the mt-sRNA test, which incorporated a fecal immunochemical test (FIT), concentration of eight RNA transcripts, and self-reported smoking status. Participants then completed a colonoscopy. The mt-sRNA test results were compared with index lesions observed on colonoscopy.

The researchers found that the mt-sRNA had a 94% sensitivity rate for detecting colorectal cancer, compared with FIT’s 77.8% sensitivity rate. The sensitivity rate for detecting advanced adenomas was 46%, compared with FIT’s 28.9% sensitivity rate. Specificity for detecting no lesions on colonoscopy was high at 88%, though lower than the FIT’s 95.7%.

Because the researchers used social media for participant recruitment, the study was limited due to its decentralized approach. Participants went to local centers for screenings, resulting in differences in physician experience, technique, and training. There were also differences in factors such as colonoscopy scheduling and bowel preparation, as well as reporting practices in the colonoscopy and pathology reports. The researchers speculate these could have contributed to variability in results. The decentralized approach also may have led to participants dropping out.

“In individuals 45 years and older, the mt-sRNA test showed high sensitivity for colorectal neoplasia (colorectal cancer and advanced adenoma) with significant improvement in sensitivity relative to the FIT. Specificity for no lesions on colonoscopy was comparable to existing molecular diagnostic tests,” the authors concluded.

Reference

Barnell EK, Wurtzler EM, La Rocca J, et al. Multitarget stool RNA test for colorectal cancer screening. JAMA Netw Open. 2023;330(18):1760–1768. doi:10.1001/jamanetworkopen.2023.22231