Single-application fecal immunochemical tests (FITs) have moderate to high sensitivity and specificity for colorectal cancer (CRC) depending on the hemoglobin positivity threshold. But the sensitivity of one-time testing for advanced adenomas is low, regardless of the assay cutoff point, a review and meta-analysis found.
Thomas F. Imperiale, MD, of Indiana University Medical Center in Indianapolis, and colleagues reported that while one-time FITs may be highly sensitive for CRC, there is also a high false-positive rate. At high specificity, these assays are only moderately sensitive for CRC.
The analysis, published in Annals of Internal Medicine, summarized the performance characteristics of one or more FITs for both CRC and advanced adenomas in average-risk persons undergoing screening colonoscopy in order to identify factors affecting these characteristics.
The researchers included 31 English-language studies published up until October 2018 with 120,255 asymptomatic screened participants and a low-to-moderate risk of bias. The mean age of participants across studies ranged from 48.2 to 64, and the sample size ranged from 284 to 21,805.
A total of 18 different FIT brands were tested, with individual studies testing from one to six assays. Performance depended on the threshold for a positive result, defined as micrograms of hemoglobin per gram (μg/g) of feces and set by the kit manufacturers or the screening programs. Cutoffs varied among studies from <10 μg/g to >20 μg/g.
In the case of CRC, a threshold of 10 μg/g resulted in sensitivity of 0.91 (95% confidence interval 0.84-0.95) and a negative likelihood ratio of 0.10 (95% CI 0.06-0.19). A threshold greater than 20 μg/g resulted in specificity of 0.95 (95% CI 0.94- 0.96) and a positive likelihood ratio of 15.49 (95% CI 9.82-22.39).
For advanced adenomas, FITs were less sensitive, yielding a sensitivity of 0.40 (95% CI 0.33-0.47) and a negative likelihood ratio of 0.67 (95% CI 0.57-0.78) at 10 μg/g. Specificity was 0.95 (95% CI 0.94-0.96), and the positive likelihood ratio was 5.86 (95% CI 3.77-8.97) at greater than 20 μg/g.
“The natural history of these lesions suggests annual transition rates to CRC of 3%-6%, implying an opportunity for detection with programmatic screening,” Imperiale and associates wrote. “Healthcare systems need to consider the quantity and quality of data for a specific FIT, comparability of the population to the study populations for that particular FIT, and the clinical and economic effects of different test thresholds on colonoscopy and systems resources to optimize FITs for early detection and prevention of CRC.”
The findings are consistent with those of systematic reviews of CRC by Lee et al. and Katsoula et al. The study could not separately determine FIT performance characteristics for proximal versus distal lesions, but last year Zorzi and colleagues reported divergent results, with lower FIT-based screening for advanced neoplasia in the proximal colon.
Study heterogeneity varied depending on the thresholds. A comparison of three different FIT assays at three different thresholds was inconclusive, with confidence intervals overlapping and comparisons across rather than within studies.
The systematic review suggested challenging directions for future FIT research, the authors said — “the most important of which is the need for a head-to-head comparison of different FITs at various thresholds for both CRC and advanced adenomas, with subgroups for proximal and distal lesions.”
In an accompanying editorial, James E. Allison, MD, of the University of California, San Francisco and Kaiser Permanente in Northern California, explained that the review and meta-analysis “may help to reassure physicians and patients about the performance of FITs for CRC detection” and that “it should be reassuring to skeptics that most countries with CRC population screening programs use FITs as their test of choice.”
Allison added that U.S. physicians need to understand the advantages of these assays as CRC screening tests and advocate to increase screening rates. “We must increase our national screening for CRC numbers especially in the vulnerable population — uninsured, underinsured, poor – and calling one screening test the best or gold standard is not helpful or true,” he told MedPage Today.
“Colonoscopy screening programs recommend colonoscopy every 10 years. FIT screening programs in the United States recommend FIT every year and allow for the discovery of advanced adenomas and early curable cancers each year,” he added.
Allison also urged changes to existing laws that allow the charging of co-pays for colonoscopy done after a positive FIT. “We need better and more consistent payment policies that insure coverage of colonoscopy after an abnormal FIT,” he said. And users should make sure that the advertised performance of the assay used has been confirmed.
Imperiale and co-authors noted that the meta-analysis had several limitations, including missing details that prevented knowing whether participants were consecutive or random, whether FIT results and colonoscopic findings were interpreted independently, and what the intervals between FIT and colonoscopy were. In addition, the inclusion of English-only studies could have led to language bias, and the study did not assess for publication bias. Furthermore, the summary-level performance characteristics applied only to one-time testing and not to serial testing, which is recommended in clinical practice. Other limitations included the study’s inability to differentiate the detection of proximal versus distal lesions and the moderate to high statistical heterogeneity for all analyses of specificity and sensitivity except for the 10 μg/g cutoff point for CRC.
Funding was primarily provided by the University of Indiana Department of Medicine.
Imperiale and co-authors reported having no conflicts of interest.
Allison reported having no conflicts of interest.