Fecal Hemoglobin Levels in Prior Negative Screening and Detection of Colorectal Neoplasia: A Dose-Response Meta-Analysis

Background & aims: Prior studies have shown that individuals with fecal hemoglobin (f-Hb) concentrations just below the positivity cutoff have an increased colorectal cancer risk compared with those with no or low f-Hb. Understanding the dose-response association between f-Hb in a prior screening round and the detection of colorectal neoplasia is crucial for tailoring risk-based screening recommendations.

Methods: We searched the literature to identify studies reporting the association between f-Hb in prior screening round and colorectal neoplasia detection in an average-risk population. Analysis involved a 2-stage approach using log-log regression models to assess dose-response relationships across studies, with effect sizes pooled using a random effects model. Heterogeneity was assessed by excluding individual studies in sensitivity analyses. Subgroup analyses examined variations in effects by outcome definitions and detection methods.

Results: This systematic review and meta-analysis included 13 studies with 4,493,672 individuals. All studies demonstrated a positive association between f-Hb in prior screenings and colorectal neoplasia detection. Pooled analysis revealed that individuals with f-Hb concentrations of 5, 10, 20, and 40 μg/g had a 3-, 5-, 8-, and 13-fold higher risk of colorectal neoplasia, respectively, compared with individuals with 0 μg/g. Although significant heterogeneity (I² = 97.5%, P < .001) was observed, sensitivity analyses confirmed the consistency of findings. Subgroup analyses indicated that f-Hb concentrations from previous negative tests were especially predictive of advanced neoplasia in subsequent screenings.

Conclusions: Our findings suggest that the risk of detecting colorectal neoplasia increases with prior f-Hb concentrations in negative tests, supporting the development of risk-stratified screening strategies based on these concentrations.