IMPORTANCE: Noninvasive tests for colorectal cancer screening must include sensitive detection of colorectal cancer and precancerous lesions. These tests must be validated for the intended-use population, which includes average-risk individuals 45 years or older.
OBJECTIVE: To evaluate the sensitivity and specificity of a noninvasive, multitarget stool RNA (mt-sRNA) test (ColoSense) test compared with results from a colonoscopy.
DESIGN, SETTING, AND PARTICIPANTS: This phase 3 clinical trial (CRC-PREVENT) was a blinded, prospective, cross-sectional study to support a premarket approval application for a class III medical device. A total of 8920 participants were identified online using social media platforms and enrolled from June 2021 to June 2022 using a decentralized nurse call center. All participants completed the mt-sRNA test, which incorporated a commercially available fecal immunochemical test (FIT), concentration of 8 RNA transcripts, and participant-reported smoking status. Stool samples were collected prior to participants completing a colonoscopy at their local endoscopy center. The mt-sRNA test results (positive or negative) were compared with index lesions observed on colonoscopy. Over the course of 12 months, individuals 45 years and older were enrolled in the clinical trial using the decentralized recruitment strategy. Participants were enrolled from 49 US states and obtained colonoscopies at more than 3800 different endoscopy centers.
MAIN OUTCOMES AND MEASURES: The primary outcomes included the sensitivity of the mt-sRNA test for detecting colorectal cancer and advanced adenomas and the specificity for no lesions on colonoscopy.
RESULTS: The mean (range) age of participants was 55 (45-90) years, with 4% self-identified as Asian, 11% as Black, and 7% as Hispanic. Of the 8920 eligible participants, 36 (0.40%) had colorectal cancer and 606 (6.8%) had advanced adenomas. The mt-sRNA test sensitivity for detecting colorectal cancer was 94%, sensitivity for detecting advanced adenomas was 46%, and specificity for no lesions on colonoscopy was 88%. The mt-sRNA test showed significant improvement in sensitivity for colorectal cancer (94% vs 78%; McNemar P = .01) and advanced adenomas (46% vs 29%; McNemar P < .001) compared with results of the FIT.
CONCLUSIONS AND RELEVANCE: 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.
TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04739722.
Screening for bowel cancer is one of few conditions that have been shown to save lives. Ways to further improve screening programs are very worthwhile.
Interesting. I am aware that a number of fecal assays other than FIT/FOBT have been developed, but I am not sure whether this performs significantly better than other options.
This is an important article. I am particularly interested in how RNA testing might fit in to a national strategy for colorectal cancer screening.
In this study, the authors performed a real-world colon cancer screening using a new multi-target stool test, this one for RNA (Cologuard looks for DNA), and in this study it appeared to be as sensitive for colorectal cancer (94%) as reported values for Cologuard. All patients received a colonoscopy as the gold standard Cologuard is priced at around $4,000. I could not find a price here, but there is evidence in the literature that Cologuard as priced is cost-effective. More screening is key. If this gets the job done, it will be worth the effort.
This large RCT of an RNA-based molecular stool test for CRC screening demonstrated higher sensitivity for non-advanced and advanced adenomas compared to DNA tests. The challenge of this trial is the overall low percentage of patients with CRC in the trial, which makes me worried about whether the trial population was a representative sample.