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

Key clinical point: Centers with adequate resources should consider lowering their threshold for positive fecal immunochemical testing (FIT).

Major finding: Pooled sensitivity for the detection of colorectal cancer rose from 69% 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.

Study details: Meta-analysis of 46 studies with 2.4 million participants and 6,478 detected cancers.

Disclosures: The National Cancer Institute and the Swiss Cancer Research Foundation provided funding. The investigators reported having no conflicts of interest.

Citation:

Selby K et al. Gastroenterology. 2019 Aug 22. doi: 10.1053/j.gastro.2019.08.023.

Commentary:

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.

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.