Shannon L. Kanis

Higher Fecal Immunochemical Test Cutoff Levels: Lower Positivity Rates but Still Acceptable Detection Rates for Early-Stage Colorectal Cancers

Background: Adjusting the threshold for positivity of quantitative fecal immunochemical tests (FIT) allows for controlling the number of follow-up colonoscopies in a screening program. However, it is unknown to what extent higher cutoff levels affect detection rates of screen-relevant neoplasia. This study aimed to assess the effect of higher cutoff levels of a quantitative FIT on test positivity rate and detection rate of early-stage colorectal cancers (CRC). Methods: Subjects above 40 years old scheduled for colonoscopy in 5 hospitals were asked to sample a single FIT (OC sensor) before colonoscopy. Screen-relevant neoplasia were defined as advanced adenoma or early-stage cancer (stage I and II). Positivity rate, sensitivity, and specificity were evaluated at increasing cutoff levels of 50 to 200 ng/mL. Results: In 2,145 individuals who underwent total colonoscopy, 79 patients were diagnosed with CRC, 38 of which were with early-stage disease. Advanced adenomas were found in 236 patients. When varying cutoff levels from ≥50 to ≥200 ng/mL, positivity rates ranged from 16.5% to 10.2%. With increasing cutoff levels, sensitivity for early-stage CRCs and for screen-relevant neoplasia ranged from 84.2% to 78.9% and 47.1% to 37.2%, respectively. Conclusions: Higher FIT cutoff levels substantially decrease test positivity rates with only limited effects on detection rates of early-stage CRCs. However, spectrum bias resulting in higher estimates of sensitivity than would be expected in a screening population may be present. Impact: Higher cutoff levels can reduce strain on colonoscopy capacity with only a modest decrease in sensitivity for curable cancers. Cancer Epidemiol Biomarkers Prev; 20(2); 272–80. ©2010 AACR.

S1123 Double Versus Single Sampling of Fecal Immunochemical Tests for Colorectal Cancer Screening; Added Value or Added Costs?

Background Fecal immunochemical tests (FITs) are state of the art in colorectal cancer(CRC) screening. Sensitivity of a single FIT for advanced neoplasia is around 50%. Theoretically, as blood loss from colon tumors can be intermittent, sensitivity of FITs could improve by double sampling. This study aims to compare the sensitivity of single FIT sampling and double FIT sampling at different cut-off values, for the detection of advanced neoplasia. Methods All subjects (≥18 years) scheduled for elective colonoscopy in three participating centers in the Amsterdam area were asked to perform FITs (OC sensor®) on two consecutive days. FIT results were compared with colonoscopy and histology as gold standard. Test performance of single FIT was compared to the sensitivity of double FIT sampling. Double FIT sampling was considered positive if one of both FITs was higher than the cut-off value. Test performances were evaluated at cut-off values ranging from 50-150ng/ml (incremental steps of 25ng/ml). Results Of 1105 subjects who performed two FITs and underwent total colonoscopy, 140 (9,4%) had advanced neoplasia (AN), of which 34 were CRC and 106 were advanced adenomas (AA). Of the CRC cases, 70% were Dukes stage A or B (stage unknown in 2). Positivity rates for single FIT ranged from 11-17%, and for double FIT from 14-23%. At the same cut-off value for positivity, sensitivity of double FIT sampling was higher than sensitivity of single FIT sampling. For any particular specificity (e.g. 90%), the sensitivity of double FIT was slightly higher than that of single FIT at a lower cut-off value (see table), but these differences were not statistically significant. Conclusions Two fold sampling of FIT does increase sensitivity for advanced neoplasia. However, at a given specificity, sensitivity of double sampling is comparable to single sampling at a lower cutoff value. Sensitivity and specificity of single and double FIT testing for the detection of advanced neoplasia

930 Comparing Three Different Strategies of Double Sampling by Fecal Immunochemical Tests for Detection of Advanced Colorectal Neoplasm's

Background Fecal Immunochemical Tests (FITs) are widely used for Colorectal Cancer (CRC) screening. Some sampling schemes use one-day FIT testing, whereas others use twoday FIT testing. Data on sensitivity and specificity of two-day FIT testing are lacking. This study aims to compare the difference in sensitivity and specificity of three different strategies of two-day FIT sampling, at different cut-off values. Methods In three hospitals in the Amsterdam area, all subjects ≥18 years who were referred for elective colonoscopy were asked to perform a FIT (OC sensor®) on two consecutive days. Colonoscopy and histology were considered as gold standard. Two-day FIT sampling was defined positive in three different ways: 1) when at least one of two FITs was above the cut-off value (FIT+), 2) when both FITs were above the cut-off value(FIT++), and 3) when the geometric mean of two FITs was above the cut-off value (FITmean). Test performance of all three strategies was evaluated at cut-off values of 50, 75 and 100ng/ml. Results In 1105 subjects with complete colonoscopy, 140 (9,4%) AN were found (34 CRCs and 106 advanced adenomas). Of the CRC cases, 70% were Dukes stage A or B (stage unknown in 2). Positivity rates for FIT+ ranged from 16-23%, for FIT++ from 10-13% and for FITmean from 13-17% (see table). At any cut-off level, FIT++ resulted in the lowest and FIT+ in the highest sensitivity. FIT++ showed a higher specificity than both other strategies (see table). Conclusions The most sensitive strategy in two-day FIT sampling is defining the test positive when at least one of both FITs passes the cut off (FIT+), whereas the highest specificity is obtained when both FITs need to be positive for calling the tests positive (FIT++). At all cut-off values, FITmean offers substantially better specificity than FIT+, while sensitivity is substantially higher than FIT++. Sensitivity and specificity of three methods to use two-day FIT sampling for the detection of advanced neoplasia

IBD: Exposure to anti-TNF agents in utero: controlling health risks.

A recent study reports on drug clearance in newborn babies after in utero exposure to anti-TNF antibodies, infliximab and adalimumab. As women with IBD are increasingly exposed to these drugs due to changing treatment paradigms and earlier diagnosis, this commentary explores these clinically important results.

T2021 Higher Cut Off Values for Fit in CRC-Screening: Less Colonoscopies, Same Detection Rates for Curable Cancers

Introduction: The Fecal Immunochemical Test(FIT) is a next generation Faecal Occult Blood Test(FOBT)and has been proposed as screening tool for Colorectal Cancer(CRC). The goal of screening is to detect CRC in an early, curable stage(i.e. Dukes A+B). Some variants of FITs produce a quantitative outcome which allows for adjusting the threshold for calling a test positive. A higher cut off value will result in less positive tests and subsequently less screenees referred for colonoscopy and thus less strain on the endoscopic capacity. However it is unknown whether a higher cut off value will impair the detection rate of(curable)colorectal cancers. Aim: To assess the effect of a higher cut off value of a quantitative FIT on the positivity rate and on the detection rate of curable early stage CRCs. Methods: All patients aged ≥18 years and scheduled for a colonoscopy in 5 participating hospitals were asked to perform a FIT(OC sensor®, Eiken chemical Co, Japan) on one bowel movement the day prior to colonoscopy. Tests of all patients were assessed using cut-off values of 50, 100, 150 and 200 ng haemoglobin per ml. For analysis of all tests, the desktop analyser “OCSENSOR μ” was used. Test results were compared with the gold standard colonoscopy. Results: In 1,897 individuals, who underwent total colonoscopy, 62 cases of colorectal cancer(3.3%) were identified. 28/62 patients were diagnosed with early stage (Dukes A+B) colorectal cancer and 31 patients with late stage(Dukes C+D). Three rectal cancers could not be accurately staged due to the effects of neo-adjuvant radiotherapy. In our total population of 1,897 individuals, the OC sensor® was positive in 8.8%, 9.8%, 11.4% and 14.0% at cut offs of 200, 150, 100, and 50 ng/ml, respectively. The detection rates for early stage CRCs ranged from 75.0% to 78.5% depending on the threshold of FIT(Table 1). Conclusions: A higher cut off value for FIT can reduce strain on colonoscopy capacity with only a slight decrease in detection rates of curable, early stage, colorectal cancers.