Key Clinical Summary

• In a retrospective analysis of 30,165 participants, fecal immunochemical test (FIT) sensitivity was higher in males than females for colorectal cancer (77.4% vs 62.0%) and advanced precancerous lesions (25.8% vs 20.2%).
• FIT thresholds yielding 95% specificity were 120 ng/mL for males and 94 ng/mL for females.
• The authors said the findings support considering different thresholds according to screening goals.

A fecal immunochemical test used in two colorectal cancer screening validation studies performed differently in men and women, according to research presented October 13 at the 2026 American College of Gastroenterology meeting. The analysis found higher FIT sensitivity in males for colorectal cancer and advanced precancerous lesions, alongside different sex-specific thresholds for achieving 95% specificity.

Study Findings

Thomas Imperiale, MD, of Indiana University School of Medicine in Indianapolis, and colleagues retrospectively analyzed cross-sectional data from the DeeP-C and BLUE-C clinical validation studies. Both studies used the same independent, quantitative comparator FIT, with a positivity threshold of 100 ng/mL (20 µg/g). The investigators compared fecal hemoglobin levels and FIT sensitivity by sex, then identified the threshold yielding 95% specificity for each group.

Among 30,165 participants, the mean age was 63.4 years, 46.6% were male, 163 (0.54%) had colorectal cancer, and 2901 (9.6%) had advanced precancerous lesions. Mean and median fecal hemoglobin levels were higher in males. FIT sensitivity was 77.4% in males versus 62.0% in females for colorectal cancer, and 25.8% versus 20.2% for advanced precancerous lesions.

Thresholds yielding 95% specificity were 120 ng/mL for males and 94 ng/mL for females. Lesion size distributions did not differ significantly by sex, but distal colorectal cancers were more frequent in males than females (69.0% vs 51.9%), as were distal advanced precancerous lesions (53.6% vs 46.4%).

In the investigators’ regression analysis, male sex was independently associated with FIT sensitivity for advanced neoplasia (odds ratio, 1.22; 95% CI, 1.02–1.47). Smoking status, body mass index of at least 30, lesion size, distal or rectal location, and histology were also associated with sensitivity.

Clinical Implications

The findings raise a practical question for colorectal cancer screening: whether one FIT positivity threshold serves the same screening goals in male and female patients. At the comparator test’s shared threshold, sensitivity for both colorectal cancer and advanced precancerous lesions was lower in females. The analysis also found a more proximal distribution of these lesions in females, while lesion size distributions were similar.

The authors concluded that the data support different thresholds depending on screening goals. Clinicians interpreting the results should also consider the study design: this was a retrospective analysis of cross-sectional validation-study data, rather than a prospective comparison of sex-specific screening strategies.

The authors reported associations with sex, lesion location and size, smoking status, body mass index, and histology.

The study provides evidence for evaluating sex-specific FIT thresholds, with the appropriate choice tied to the intended screening goal.

Reference: Imperiale T, Porter K, Limburg P. Performance characteristics of fecal immunochemical tests in males and females: should the threshold vary? Abstract 19. Presented at: American College of Gastroenterology Annual Scientific Meeting; Nashville, Tennessee. October 12-14, 2026.