Fecal immunochemical tests (FITs) show significant differences in colorectal cancer detection rates between men and women, according to a study presented at the American College of Gastroenterology 2026 Annual Scientific Meeting in Nashville, Tennessee. Researchers analyzed data from 30,165 participants across the DeeP-C and BLUE-C clinical validation studies to evaluate whether standard positivity thresholds perform equally for both genders.
Data Analysis From Clinical Validation Studies
The retrospective analysis examined prospective cross-sectional data from multitarget stool DNA and next-generation multitarget stool DNA FIT test trials. Each test used an independent quantitative comparator FIT with a standard positivity threshold of 100 ng/mL, or 20 µg/g. Among the 30,165 participants—who had a mean age of 63.4 years and included 46.6% males—researchers identified 163 individuals with colorectal cancer and 2,901 with advanced precancerous lesions.
Men exhibited higher mean and median fecal hemoglobin levels than women. At the 100 ng/mL threshold, FIT sensitivity for colorectal cancer reached 77.4% in males compared to 62.0% in females, while sensitivity for advanced precancerous lesions hit 25.8% for men and 20.2% for women. Conversely, test specificity was slightly lower for men at 94.2% versus 95.3% for women.
Tumor Location and Sensitivity Disparities
Thomas Imperiale, MD, of the Indiana University School of Medicine in Indianapolis, reported that male gender was independently associated with a higher risk for advanced neoplasia sensitivity with an odds ratio of 1.22. Distal colorectal cancers were more frequent in males at 69.0% compared to 51.9% in females, while females showed a higher proportion of proximal cancers at 48.1% versus 31% for males. For proximal locations, cancer sensitivity was significantly higher in males at 80.8% compared to 50.0% in females.
To match male cancer sensitivity, the threshold in women would need a reduction to 12 ng/mL, which would drop specificity to 75.7%. Reaching equal advanced precancerous lesion sensitivity would require lowering the female threshold to 65 ng/mL, yielding a specificity of 92.8%. Achieving a uniform 95% specificity requires thresholds of 120 ng/mL for males and 94 ng/mL for females.
Screening goals complicate gender-based threshold decisions
Imperiale explained that deciding whether to implement gender-based thresholds depends entirely on the primary goal of screening. If the objective is equal detectability between sexes, thresholds should differ, but systems must account for downstream consequences such as increased positive tests and colonoscopy referrals. Michael Dougherty, MD, an attending gastroenterologist at University of North Carolina REX Digestive Healthcare in Chapel Hill, noted that utilizing different versions of a test or separate interpretations adds unwanted complexity to a process designed to maximize screening uptake.
Common Questions About FIT Screening Differences
Should women stop using standard fecal immunochemical tests?
Dougherty emphasized that women should continue using current FIT screenings, noting that any negative result in a patient with developing alarm symptoms still requires prompt clinical evaluation.
What factors outside of gender influence test sensitivity?
Multivariate analysis identified several risk factors for advanced neoplasia sensitivity, including a body mass index of 30 or higher, current or former smoking status, larger lesion size, and distal or rectal locations.
What specific thresholds produce 95% specificity?
Data from the study indicate that a 120 ng/mL threshold yields 95% specificity in males with a 77.1% cancer sensitivity, while a 94 ng/mL threshold achieves 95% specificity in females with a 63.3% cancer sensitivity.