Simple SummaryRecently, the cases of colorectal cancers has been rising in younger age (<50) individuals. Although current guidelines recommend colorectal cancer screening should be initiated at age 45 instead of 50, the optimal approach of colorectal cancer screening is not clear. This article investigates the efficacy of fecal immunochemical test (FIT), which detects occult blood in stool, in predicting advanced colorectal polyps and tumors among people aged 40–49. The findings suggest FIT is useful to identify such people with high risk to have advanced colorectal lesions. Hence, FIT may be considered as the first-line screening tool for these people, and further comparative study between FIT and colonoscopy will be of great value.AbstractBackground: The incidence of early-onset colorectal cancer (CRC) is increasing. Many guidelines recommend initiating screening at 45 years. This study investigated the detection rate of advanced colorectal neoplasm (ACRN) by using fecal immunochemical tests (FITs) in individuals aged 40–49 years. Methods: PubMed, Embase, and Cochrane Library databases were searched from inception to May 2022. The primary outcomes were the detection rates and positive predictive values of FITs for ACRN and CRC in people aged 40–49 (younger age group) and ≥50 years (average risk group). Results: Ten studies with 664,159 FITs were included. The FIT positivity rate was 4.9% and 7.3% for the younger age and average risk groups, respectively. Younger individuals with positive FIT results had significantly higher risks of ACRN (odds ratio [OR] 2.58, 95% confidence interval [CI] 1.79–3.73) or CRC (OR 2.86, 95% CI 1.59–5.13) than did individuals in the average-risk group, regardless of FIT results. Individuals aged 45–49 years with positive FIT results had a similar risk of ACRN (OR 0.80, 95% CI 0.49–1.29) to that of people aged 50–59 years with positive FIT results, although significant heterogeneity was observed. The positive predictive values of the FIT were 10–28.1% for ACRN and 2.7–6.8% for CRC in the younger age group. Conclusion: The detection rate of ACRN and CRC based on FITs in individuals aged 40–49 years is acceptable, and the yield of ACRN might be similar between individuals aged 45–49 and 50–59 years. Further prospective cohort and cost-effective analysis are warranted.