Multitarget Stool RNA Test for Colorectal Cancer Screening.

Area of Science:

• Oncology
• Gastroenterology
• Molecular Diagnostics
• Medical Device Development

Background:

• Effective noninvasive colorectal cancer (CRC) screening requires sensitive detection of both CRC and precancerous lesions.
• Validated screening tests are crucial for average-risk individuals aged 45 and older.
• Existing noninvasive tests, like the fecal immunochemical test (FIT), have limitations in sensitivity for certain lesions.

Purpose of the Study:

• To evaluate the sensitivity and specificity of a novel noninvasive multitarget stool RNA (mt-sRNA) test (ColoSense) for colorectal neoplasia.
• To compare the performance of the mt-sRNA test against colonoscopy results in a large, diverse population.
• To assess the improvement in sensitivity for colorectal cancer and advanced adenomas compared to FIT.

Main Methods:

• A phase 3, blinded, prospective, cross-sectional clinical trial (CRC-PREVENT) involving 8920 participants aged 45 years and older.
• Participants underwent the mt-sRNA test, which combined FIT, 8 RNA transcripts, and smoking status, followed by colonoscopy.
• Decentralized recruitment via social media and a nurse call center ensured broad geographic and demographic representation across the US.

Main Results:

• The mt-sRNA test achieved 94% sensitivity for colorectal cancer and 46% sensitivity for advanced adenomas.
• Specificity for no lesions on colonoscopy was 88%.
• The mt-sRNA test demonstrated significant improvements in sensitivity for both colorectal cancer (94% vs. 78%) and advanced adenomas (46% vs. 29%) compared to FIT alone.

Conclusions:

• The noninvasive mt-sRNA test exhibits high sensitivity for detecting colorectal neoplasia in individuals aged 45 and older.
• This test offers a significant advancement in sensitivity over FIT for both cancer and advanced adenomas.
• The specificity is comparable to existing molecular diagnostic tests, positioning it as a promising tool for CRC screening.