Consistent Major Differences in Sex- and Age-Specific Diagnostic Performance among Nine Faecal Immunochemical Tests Used for Colorectal Cancer Screening

Abstract

Evidence on diagnostic performance of faecal immunochemical tests (FITs) by sex and age is scarce. We aimed to evaluate FIT performance for detection of advanced colorectal neoplasia (AN) by sex and age across nine different FIT brands in a colonoscopy-controlled setting. The faecal samples were obtained from 2042 participants of colonoscopy screening. All eligible cases with AN (n = 216) and 300 randomly selected participants without AN were included. Diagnostic performance for detection of AN was assessed by sex and age (50–64 vs. 65–79 years for each of the nine FITs individually and for all FITs combined. Sensitivity was consistently lower, and specificity was consistently higher for females as compared with males (pooled values at original FIT cutoffs, 25.7% vs. 34.6%, p = 0.12 and 96.2% vs. 90.8%, p < 0.01, respectively). Positive predictive values (PPVs) were similar between both sexes, but negative predictive values (NPVs) were consistently higher for females (pooled values, 91.8% vs. 86.6%, p < 0.01). Sex-specific cutoffs attenuated differences in sensitivities but increased differences in predictive values. According to age, sensitivities and specificities were similar, whereas PPVs were consistently lower and NPVs were consistently higher for the younger participants. A negative FIT is less reliable in ruling out AN among men than among women and among older than among younger participants. comparisons of measures of diagnostic performance among studies with different sex or age distributions should be interpreted with caution.

A Point-of-Care Faecal Test Combining Four Biomarkers Allows Avoidance of Normal Colonoscopies and Prioritizes Symptomatic Patients with a High Risk of Colorectal Cancer

“…The NPV of a negative result in the four biomarkers for the diagnosis of significant pathology was higher in females (97.3% vs 91.9% in males) and in younger patients (98.5% in patients under 50 years old vs 93% in older patients). This better performance of the faecal test in women and younger patients has been previously reported in similar studies [41]. A triage strategy based in the POC test would have avoided 36.8% (210/571) of colonoscopies without missing any CRC or IBD case.…”

An efficient strategy for evaluating new non-invasive screening tests for colorectal cancer: the guiding principles

“… 54 55 Most are qualitative with the positivity threshold set by the manufacturer and have not been subjected to large population studies, 56 but several are quantitative, allowing for adjustment of the positivity threshold, and have been extensively studied. 57–59 …”

“…54 55 Most are qualitative with the positivity threshold set by the manufacturer and have not been subjected to large population studies, 56 but several are quantitative, allowing for adjustment of the positivity threshold, and have been extensively studied. [57][58][59] Setting analytical specifications of a new test where the technology incorporates new biomarkers or biomarker combinations will initially depend very much on phases I and II evaluations, where positivity criteria are usually based on the combination that best discriminates between CRC and non-CRC states. Typically, these generate diagnostic sensitivities that are not maintained in validation studies undertaken in phase III studies (typical screening populations) and positivity thresholds might need adjustment.…”

Interval cancer after two rounds of a Swedish population-based screening program using gender-specific cut-off levels in fecal immunochemical test

“…The reason for the lower FIT in women is unclear but could be related to a higher rate of lesions in the proximal colon that are less prone to bleeding or a longer colonic transit time in women, leading to a larger degree of fecal hemoglobin degradation. [10][11][12][13] If the lower FIT in women was due to obstipation, the gender difference would be greater in CRCs in the proximal colon than in distal segments. On the contrary, a study from the Scottish bowel screening program showed significantly lower FIT levels in women only in the left-sided CRCs.…”