S588 Laboratory-Performed FIT-Enhanced Accuracy and Compliance With mt-sRNA Test for Colorectal Cancer Screening

Introduction: Fecal immunochemical tests (FIT) and multi-target stool DNA tests require swabbing stool from a toilet or bucket before mailing the sample to a central lab as part of noninvasive CRC testing. At-home sampling by untrained individuals introduces complexity to stool collection and increases the risk of human error, environmental exposure, and transit-related degradation. Requiring subjects to handle stool is also a potential barrier to adherence. The multi-target stool RNA test (mt-sRNA) is the only test that is Food and Drug Administration-approved for the detection of both CRC and advanced adenomas (AA) that does not require patients to perform an at-home FIT swab. Instead, trained technicians complete the FIT swab in the laboratory after the sample is received. Methods: As part of the CRC-PREVENT clinical trial, subjects produced a stool sample and completed an at-home FIT swab prior to undergoing a colonoscopy. Stool samples were shipped to a centralized laboratory. Banked residual stool samples were swabbed by laboratory technicians to evaluate the in-lab FIT method. At-home and in-lab FITs were analyzed using the same process and positivity threshold. Both FIT results were compared to each other and to colonoscopy to assess concordance, sensitivity, and specificity. Results: A total of 1,079 stool samples were analyzed using both at-home and in-lab FIT methods. While ∼1% of at-home FITs fail due to pre-analytical errors, no in-lab FITs failed analysis. Concordance of results between tests was 93%. Among the 20 subjects with CRC, both at-home and in-lab methods detected 75% (n = 15). Among the 231 subjects with AA, the at-home method detected 33% (n = 76) and the in-lab method detected 38% (n = 88). Positive percent agreement (PPA) for colorectal neoplasia was 87%. Among the 791 subjects with negative findings, specificity for the at-home and in-lab methods were 94% and 95%, respectively. Negative percent agreement (NPA) was 98%. Among the 75 samples with discrepant FIT results, the in-lab FIT more closely aligned with colonoscopy findings relative to the at-home FIT (60% vs 40%; P < 0.01). Conclusion: Our findings suggest that in-lab FIT performance combined with the molecular component of the mt-sRNA test may enhance the diagnostic accuracy of the multi-target test. The in-lab method may also improve test adherence and reduce inadequate sampling.