One- versus two-sample fecal immunochemical testing for colorectal cancer screening: a systematic review and meta-analysis of participation, diagnostic performance, and cost-effectiveness.

BACKGROUND

Whether collecting one or two fecal samples for immunochemical testing (FIT) optimizes colorectal cancer screening outcomes remains unclear.

METHODS

We systematically searched multiple databases until October 2025 for studies directly comparing 1-FIT and 2-FIT strategies. Pooled risk ratios (RRs) with 95% confidence intervals (CIs) were calculated for dichotomous outcomes.

RESULTS

Five studies (n = 45,888) and three economic evaluations were included. Participation was higher with 1-FIT (RR = 1.05, P < 0.0001), while 2-FIT had a higher positivity rate (RR = 0.65, P < 0.0001). Although 2-FIT detected more CRC (RR = 0.62, P = 0.02), advanced neoplasia and advanced adenoma detection were similar. The 2-FIT strategy had higher sensitivity (RR = 0.64, P = 0.04) but lower specificity (RR = 1.70, P < 0.001) than 1-FIT. A pivotal finding was that the 1-FIT strategy demonstrated a superior positive predictive value (PPV) for both advanced neoplasia (RR = 1.21, P = 0.004) and advanced adenoma (RR = 1.41, P < 0.0001), which translated into a substantially lower demand for colonoscopy (RR = 0.64, P < 0.0001) Economic evaluations consistently favored 1-FIT across different healthcare systems.

CONCLUSION

Although the 2-FIT strategy improves test sensitivity, it fails to enhance advanced neoplasia detection while substantially increasing colonoscopy demand due to its reduced positive predictive value. In contrast, the 1-FIT strategy preserves screening efficacy with superior participation rates, resource utilization, and cost-effectiveness. We recommend 1-FIT as the preferred strategy in settings with constrained colonoscopy resources, while reserving 2-FIT for resource-abundant environments where maximizing sensitivity justifies the additional economic and operational costs (Scheme 1).

TRIAL REGISTRATION: The research protocol was prospectively registered in the PROSPERO registry, bearing the registration identifier CRD420251153202.