Basic variables at different positivity thresholds of a quantitative immunochemical test for faecal occult blood

Abstract

Objectives: Screening by faecal occult blood testing (FOBT) is effective in decreasing mortality and incidence of colorectal cancer (CRC). Immunochemical tests have proved to be more cost effective than guaiac FOBTs. The latex agglutination test (LAT) has the advantage of being a fully automated, quantitative test. The aim of this study is to interpret the overall experience with LAT according to different positivity thresholds. Setting: A population based screening programme is currently running involving subjects aged 50-70, invited every 2 years to have an FOBT. LAT is the standard screening test and has a positivity threshold for further diagnostic tests of 100 ng haemoglobin/ml of sample solution. Methods: Positivity rates, detection rates for CRC high risk adenomas, and positive predictive values for CRC, high risk adenomas, and low risk adenomas were calculated for several positivity thresholds. Results: 19 132 attendances at screening were recorded (11 774 at first screening, 7358 at subsequent screenings). Progressively increasing the positivity threshold from 100 to 200 ng/ml showed (a) a decrease in positivity rate; (b) a decrease in detection rates for CRC or high risk adenomas; (c) an increase in positive predictive values for cancer; (d) an increase in positive predictive value for high risk adenomas. Conclusions: Increasing the positivity threshold of the LAT reduces recall rate and improves positive predictive value for cancer or high risk adenomas but substantially decreases the detection rate of CRC and high risk adenomas. For this reason increasing the positivity cut off for LATs is not advisable. On the other hand decreasing the positivity threshold would increase recall rate and sensitivity of screening. Careful evaluation of sensitivity of the quantitative results of the LAT for interval cancers is needed to definitively assess the optimal positivity threshold for LATs in population based screening programmes.

Screening for colorectal cancer: random comparison of guaiac and immunochemical faecal occult blood testing at different cut-off levels

“…Number needed to screen was calculated as the number of complete screening tests needed to find one advanced neoplasia or CRC. Differences in PPV between sexes or age groups in the FIT arm were described for a cut-off of 100 ng ml À1 , as this cut-off value is most commonly used (Castiglione et al, 2002;Vilkin et al, 2005;van Rossum et al, 2008).…”

“…Another advantage of FIT is the quantitative test results, which allows determining an optimal cut-off value for a nation-wide screening programme (Castiglione et al, 2002;Wong et al, 2003;Guittet et al, 2007;Levi et al, 2007;Fraser et al, 2008). The cut-off value for a positive test can be based on a positivity rate that meets the available colonoscopy resources.…”

A new insight into fecal hemoglobin concentration‐dependent predictor for colorectal neoplasia

“…While the fecal immunochemical test (FIT) is widely used in population-based screening for colorectal neoplasia and is effective in reducing colorectal cancer mortality through early detection, [1][2][3][4][5][6][7][8][9][10][11][12] it has been not yet known whether the detailed information on quantitative fecal hemoglobin concentration (FHbC) available with the FIT might also be of use for predicting the risk of colorectal neoplasia. Unfortunately, because clinical practice is to select subjects with FHbC greater than a set cut-off for further clinical investigation the precise value of FHbC, although measured and often reported, is largely neglected.…”

False negative fecal occult blood tests due to delayed sample return in colorectal cancer screening

“…As threshold for positivity, the manufacturer recommends a cut-off value of 100 ng/ml, applied in several studies. [7][8][9][10][11][12] The literature as well as data provided by the manufacturer show that the test results of the OC-Sensor 1 are reliable in the range from 50 to 2,000 ng/ml. 2 In a previous publication, we compared the guaiac FOBT Hemoccult 1 with the iFOBT OC-Sensor 1 .…”

“…13 For generalizability, we also present data concerning a cut-off value of 100 ng/ml in the results and the tables, which were applied in several studies. [7][8][9][10][11][12] Colonoscopy and lesions All colonoscopies were performed by experienced gastroenterologists using conscious sedation with midazolam. If the cecum could not be reached during the initial colonoscopy, the procedure was repeated usually under propofol anesthesia.…”