Risk factors for false positive and for false negative test results in screening with fecal occult blood testing

Abstract

Differences in the risk of a false negative or a false positive fecal immunochemical test (FIT) across subgroups may affect optimal screening strategies. We evaluate whether subgroups are at increased risk of a false positive or a false negative FIT result, whether such variability in risk is related to differences in FIT sensitivity and specificity or to differences in prior CRC risk. Randomly selected, asymptomatic individuals were invited to undergo colonoscopy. Participants were asked to undergo one sample FIT and to complete a risk questionnaire. We identified patient characteristics associated with a false negative and false positive FIT results using logistic regression. We focused on statistically significant differences as well as on variables influencing the false positive or negative risk for which the odds ratio exceeded 1.25. Of the 1,426 screening participants, 1,112 (78%) completed FIT and the questionnaire; 101 (9.1%) had advanced neoplasia. 102 Individuals were FIT positive, 65 (64%) had a false negative FIT result and 66 (65%) a false positive FIT result. Participants at higher age and smokers had a significantly higher risk of a false negative FIT result. Males were at increased risk of a false positive result, so were smokers and regular NSAID users. FIT sensitivity was lower in females. Specificity was lower for males, smokers and regular NSAID users. FIT sensitivity was lower in women. FIT specificity was lower in males, smokers and regular NSAID users. Our results can be used for further evidence based individualization of screening strategies.Colorectal cancer (CRC) is one of the leading causes of cancer related death. 1 Detecting cancer or one of its precursors at an early stage can prevent premature death and may reduce cancer morbidity, since treatment for earlier-stage cancers is less aggressive than that for more advanced stage cancers. 2 The high incidence of CRC, the high burden of disease, the availability of screening tests and of effective treatment of adenomas make CRC a likely candidate for population screening.Colonoscopy is the reference standard for the detection of advanced adenoma and cancer in CRC screening. As it is a burdensome and costly procedure, fecal immunochemical test (FIT) is often used as a noninvasive triaging test for colonoscopy in CRC screening programs. Given its considerable false negative rate in the detection of advanced neoplasia, FIT should be applied at regular intervals for an optimal preventive effect. 3 With a specificity of 94% at the 50 ng/ml cut off, the accuracy of FIT based screening is suboptimal. 3 A

Nonsteroidal Anti-Inflammatory Drug-Induced Colopathy in a Colorectal Cancer Screening Program

“…If this is the case, the question remains open as to how long this should be done beforehand. In 2 clinical trials, the specificity of the iFOBT was lower in regular NSAID users [7, 8]. This conclusion is in stark contrast to a multivariate analysis conducted on 193 veterans that found no association between regular use of NSAID and a false-positive iFOBT (OR 0.85) [9].…”

Gender Differences in Fecal Immunochemical Test Performance for Early Detection of Colorectal Neoplasia

“…Both studies reported a higher test sensitivity in men. 18,19 Furthermore, the higher FPR in men may be the result of a lower test specificity. Specificity is defined by the proportion of people without the disease who also test negative.…”

“…This is in line with the results of the 2 aforementioned colonoscopy screening studies. 18,19 In addition, we calculated the FPR for the subjects with a positive FIT who had no adenoma or CRC at follow-up colonoscopy (ie, only hyperplastic polyps or no findings at all). After also including the nonadvanced adenomas, we did not see any differences between men and women for the different cut-off levels (Appendix 4).…”

“…Men showed higher detection rates of advanced neoplasia than women for the full range of FIT cut-off levels in the first round, and therefore the NNscreen to find an advanced neoplasia was significantly lower in men (Table 1). At a cut-off level of 10 mg Hb/g feces, the NNscreen to detect 1 subject with advanced neoplasia was 23 (95% CI, [19][20][21][22][23][24][25][26][27] in men and 46 (95% CI, 37-59) in women (P < .001). In the second round, men also tended to have higher detection rates of advanced neoplasia compared with women, but these differences were only significant at cut-off levels of 10 10 mg Hb/g feces, 20 mg Hb/g feces, and 25 mg Hb/g feces, respectively (Table 1 and Appendixes 2 and 3).…”

“…18 Another study that compared FIT with primary screening colonoscopy also found a higher sensitivity of FIT in men. 19 The aforementioned data were obtained from studies with colonoscopy as a primary screening tool and might have a different underlying risk than the (screening-naive) population screened with FIT.…”