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Threshold for positivity affects FIT sensitivity for detecting CRC, advanced adenomas

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Many screening programs could lower the positivity threshold

Quantitative fecal immunochemical tests or FITs are the most recent incarnation of screening for colorectal cancer (CRC) through the identification of occult blood in stool. Older versions of such tests were the first screening modalities shown to decrease both the incidence and mortality of CRC. FITs are much more sensitive for both CRC and advanced adenomas than are those early occult blood tests. They also are among the least costly and most easily employed CRC screening modalities. Given the quantitative nature of FITs, the question has remained as to what positivity threshold should be employed to achieve the optimal balance of sensitivity and specificity.

Dr. Reid M. Ness

The current study by Selby et al. examined data from 46 studies and 2.4 million participants from 12 countries. The authors found that by lowering the positivity threshold to less than 10 mcg/g from greater than 10 mcg/g but less than 20 mcg/g, the sensitivity for CRC increased from 69% to 80% and for advanced adenomas from 21% to 31%, with a trivial fall in specificity from 94% to 91%. They also found that neither sex nor age significantly altered these outcomes in the minority of studies that stratified by these demographics. These outcomes suggest that screening programs should lower the positivity threshold for FITs to less than 10 mcg/g from the current less than 20 mcg/g recommended by the U.S. Multi-Society Task Force on Colorectal Cancer Screening.

Future studies should examine more carefully demographic effects on FIT performance to determine if different positivity thresholds need to be employed in different demographic groups.

Reid M. Ness, MD, MPH, is an associate professor in the division of gastroenterology, hepatology and nutrition, department of medicine, Vanderbilt University Medical Center and at the Veterans Affairs Tennessee Valley Healthcare System, Nashville campus. He is also an investigator in the Vanderbilt-Ingram Cancer Center. Dr. Ness has no financial relationships to disclose.



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.

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