Diagnostic Accuracy and Colonoscopy-Sparing Potential of RAID-CRC Screen After a Positive Faecal Immunochemical Test

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 cross-sectional diagnostic accuracy study included participants with FIT ≥ 100 ng haemoglobin/mL and colonoscopy as reference standard. RAID-CRC Screen was analysed from residual FIT-buffer material. The primary analysis included evaluable assays and complete colonoscopy. An additional intention-to-diagnose analysis assigned non-evaluable results to colonoscopy referral. Comparisons with data-derived alternative FIT thresholds were exploratory. Results: Among 1291 participants in the primary analysis, 34 (2.6%) had CRC and 441 (34.2%) advanced neoplasia. RAID-CRC Screen was positive in 1087 (84.2%). Sensitivity was 94.1% (95% CI, 80.3–99.3%) for CRC and 87.5% (84.1–90.5%) for advanced neoplasia; specificities were 16.1% (95% CI, 14.1–18.2%) and 17.5% (95% CI, 15.0–20.3%), respectively. RAID-CRC Screen after FIT100 would avoid 204 colonoscopies (15.8%; 95% CI, 13.9–17.9%) while missing two CRCs and 55 advanced neoplasms. FIT118 alone would avoid 149 colonoscopies (11.5%), with CRC sensitivity of 100.0% (95% CI, 89.7–100.0%) and advanced neoplasia sensitivity of 92.3% (95% CI, 89.4–94.6%). In the intention-to-diagnose analysis (1312), including 21 non-evaluable results, colonoscopy reduction was 15.5% (95% CI, 13.6–17.6%), with the same two CRCs not referred. Conclusions: RAID-CRC Screen triage reduced modelled colonoscopy referrals at the cost of missed CRCs and advanced neoplasia. FIT118 alone avoided fewer colonoscopies while retaining all observed CRCs. These exploratory comparisons do not establish superiority or the safety of withholding colonoscopy.