Clinical Validation of a Simplified, Scrape-Free Collection Method for Multitarget Stool RNA Testing in Colorectal Cancer Screening.

[BACKGROUND AND AIMS] 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.

[METHODS] 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.

[RESULTS] 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%.

[CONCLUSIONS] 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.