Abstract
Background/Objectives: Faecal immunochemical test (FIT)-based colorectal cancer (CRC) screening generates many colonoscopy referrals without advanced neoplasia. We evaluated RAID-CRC Screen, a qPCR-based faecal bacterial signature, as second-line triage after positive FIT in the Galician population-based screening programme. Methods: This prospective diagnostic accuracy study included participants aged 50–69 years with FIT ≥100 ng haemoglobin/mL buffer and colonoscopy as reference standard. RAID-CRC Screen was analysed from residual FIT-buffer material. Alternative FIT thresholds were compared with RAID-CRC Screen triage. Results: Among 1296 participants, 33 (2.5%) had CRC and 444 (34.3%) advanced neoplasia. RAID-CRC Screen was positive in 1161 (89.6%). Sensitivity was 97.0% (95% CI, 84.2–99.9%) for CRC and 91.2% (88.2–93.7%) for advanced neoplasia; specificities were 10.6% and 11.3%, respectively. RAID-CRC Screen after FIT100 would avoid 135 colonoscopies (10.4%), while missing one CRC and 39 advanced neoplasms. FIT118 alone would avoid 147 colonoscopies (11.3%), detect all 33 CRCs, and provide 92.3% sensitivity for advanced neoplasia. Conclusions: RAID-CRC Screen preserved high CRC sensitivity but, at FIT100, did not provide a more favourable observed trade-off than modestly increasing the FIT threshold.