Thresholds for positivity affected the sensitivity and (to a lesser extent) the specificity of quantitative fecal immunochemical tests used in the detection of colorectal cancer, which suggests that centers should consider lowering their thresholds for positivity if they have sufficient resources to handle an increase in follow-up colonoscopies, researchers wrote in Gastroenterology.
“Additional data are needed regarding the influence of sex and age on test performance,” wrote Kevin Selby, MD, of Kaiser Permanente Division of Research in Oakland, Calif., together with his associates. Additional studies also should evaluate the effect of a quantitative threshold of 10 mcg of hemoglobin per gram of feces and multiple rounds of annual testing, they added.
Fecal immunochemical tests (FITs) are recommended for colorectal cancer screening because they are diagnostically superior and are associated with higher participation rates, compared with guaiac fecal occult blood tests, the investigators noted. For screening, the optimal positivity threshold for quantitative FIT remains controversial, is likely to vary by sex and age, and also may be adjusted to reflect local health care resources. To more closely evaluate the correlates and effects of FIT cutoffs for sensitivity, the researchers searched MEDLINE, EMBASE, and the Database of Abstracts of Reviews of Effects for articles on the use of FIT for asymptomatic (screening) colorectal cancer detection in adults. This method identified 46 studies with 2.4 million participants and 6,478 detected cancers. The researchers then calculated sensitivity, specificity, numbers of detected cancers, advanced adenomas, and positive test results at positivity thresholds of up to 10 mcg, 10-20 mcg, 20-30 mcg, and more than 30 mcg of hemoglobin per gram of feces. They also examined subgroups stratified by sex and age.
The pooled sensitivity for the detection of colorectal cancer rose from 69% (95% confidence interval, 63%-75%) at a positivity threshold of more than 10 and up to 20 mcg of hemoglobin per gram of feces, to 80% at a positivity threshold of 10 mcg or less of hemoglobin per gram of feces. “At these [same] threshold values, sensitivity for detection of advanced adenomas increased from 21% (95% CI, 18%-25%) to 31% (95% CI, 27%-35%), whereas specificity decreased from 94% (95% CI, 93%-96%) to 91% (95% CI, 89%-93%),” the researchers wrote.
Only three studies stratified results by sex, and these found no statistical difference in pooled sensitivity for detecting colorectal cancer among men (77%) versus women (81%). Age, too, was stratified in only three studies and did not significantly correlate with sensitivity. “More research is needed to precisely establish FIT thresholds for each sex and age subgroup,” the researchers said.
The National Cancer Institute and the Swiss Cancer Research Foundation provided funding. The investigators reported having no conflicts of interest.
SOURCE: Selby K et al. Gastroenterology. 2019 Aug 22. doi: 10.1053/j.gastro.2019.08.023.