Clinical Validation of a Simplified, Scrape-Free Collection Method for Multitarget Stool RNA Testing in Colorectal Cancer Screening.
Abstract
Most colorectal cancer (CRC) screening tests, including fecal immunochemical (FIT) and multitarget stool DNA tests, require patients to scrape a stool sample at home before mailing it to a central lab. This requirement not only deters screening adherence but can also introduce risks of human error, environmental exposure, and transit-related issues. The multitarget stool RNA test (mt-sRNA), which comprises a FIT component and an RNA molecular component, is the only FDA-approved stool-based test for the detection of both CRC and advanced adenomas (AA) that does not require patients to perform an at-home FIT. Instead, trained technicians complete the FIT in the laboratory after the sample is received. This study evaluates the comparability of at-home and in-laboratory FIT in relation to mt-sRNA test performance.
To assess comparability between the 2 FIT methods, banked residual stool samples from the mt-sRNA test pivotal clinical trial (CRC-PREVENT) were used. As part of clinical trial requirements, subjects were required to collect a stool sample using the mt-sRNA collection kit and complete an at-home FIT swab before shipping the sample back to the laboratory. Patients were subsequently required to complete a screening colonoscopy. Residual stool was sampled using the in-laboratory FIT. Both FIT collection methods (at-home and in-laboratory) were analyzed identically. FIT results were compared with each other and with colonoscopy, to assess concordance, sensitivity, and specificity.
A total of 1079 stool samples were tested using both at-home and in-laboratory FIT methods. Overall concordance was 93%. Among 20 CRC cases, the sensitivity for both methods was 75% (n=15). For 231 AA cases, sensitivity for the at-home and in-laboratory FIT was 33% and 38%, respectively. Positive percent agreement (PPA) for colorectal neoplasia was 87%. Among 791 subjects with negative findings, specificity for the at-home and in-laboratory FIT was 94% and 95%, respectively. For subjects with negative findings, the negative percent agreement (NPA) was 98%. When incorporating the in-laboratory FIT into the mt-sRNA test, method-calibrated CRC and AA sensitivities were 94% and 48%, respectively. Method-calibrated specificity for no lesions on colonoscopy was 90%.
Our findings suggest that in-laboratory FIT performance may enhance the diagnostic accuracy of the mt-sRNA test. The in-laboratory method may also reduce inadequate sampling and improve patient ease of use.
EDRN PI Authors
Medline Author List
- Barnell EK
- Carethers JM
- Ghannam R
- Gupta S
- Kruse K
- Levin TR
- Lieberman DA
- Shaukat A