FIT as a cornerstone of CRC screening: Optimization for advanced neoplasia.

29 Background: Colorectal cancer (CRC) remains as a leading cause of cancer-related morbidity as well as mortality worldwide. Effective screening strategies are needed for early detection of CRC and also for its precursors in the form of advanced neoplasia (AN). Fecal immunochemical testing (FIT) is widely used for non-invasive screening, but its diagnostic accuracy for CRC and especially advanced neoplasia (AN) remains variable across studies. Methods: We conducted a systematic review and meta-analysis in accordance with PRISMA guidelines. PubMed, Embase, and Cochrane Library were searched from inception to July 2025 for studies comparing FIT against colonoscopy in average-risk, asymptomatic adults aged >50 years. After deduplication, 231 articles were screened, of which 11 met eligibility criteria. Data were extracted into 2×2 tables and pooled using a bivariate random-effects model to estimate sensitivity, specificity, likelihood ratios, and diagnostic odds ratio (DOR) with 95% confidence intervals. Study quality was appraised using the QUADAS-2 tool. Results: Across 11 Studies, FIT detected CRC with a pooled sensitivity of 0.74 (95% CI, 0.63–0.83) and specificity of 0.93 (95% CI, 0.88–0.96), corresponding to a positive likelihood ratio (LR+) of 10.10 and DOR of 36.54. For CRC+AN , sensitivity fell to 0.29 (95% CI, 0.23–0.37) with specificity of 0.94 (95% CI, 0.91–0.97). These findings indicate strong ability to confirm CRC when FIT is positive but limited capacity to exclude advanced neoplasia. Assay threshold reduction improved sensitivity at the expense of specificity, while increasing threshold improved specificity, but more AN cases were missed. Conclusions: FIT demonstrates high specificity but only moderate sensitivity for detecting CRC, which supports its role in population based screening and functioning as an effective triage tool that reduces unnecessary colonoscopies. Nonetheless, because of single-sample FIT’s low sensitivity in detecting AN carries the risk of under-detecting AN. Strategies such as repeated annual testing/ multiple-sample FITs, or integration with validated clinical risk models may enhance diagnostic yield. Overall, FIT remains a cornerstone of CRC screening but its limited sensitivity for precancerous lesions underscores the need for optimization, with screening programs required to balance improved detection yield against increased colonoscopy demand. Outcomes CRC only CRC + AN Sensitivity (95% CI) 0.74 (0.63–0.83) 0.29 (0.23–0.37) Specificity (95% CI) 0.93 (0.88–0.96) 0.94 (0.91–0.97) LR+ (95% CI) 10.10 (6.48–15.72) 5.15 (3.86–6.89) LR– (95% CI) 0.28 (0.19–0.41) 0.75 (0.70–0.81) DOR (95% CI) 36.54 (21.34–62.57) 6.87 (5.27–8.95)