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Clinical literature and commentary point to a new protocol for evaluating fecal immunochemical testing (FIT) and how well this modality flags colorectal cancer (CRC). Collectively, two studies found that FIT performs poorly in identifying early-stage CRC but serves some benefit as a periodic screening tool. This research provides “additional valuable information to the body of high-quality comparative evidence about the diagnostic accuracy of FIT screening compared with other fecal tests or colonoscopy,” Carlo Senore, MD, and Manuel Zorzi, MD, wrote in a related editorial.

Both studies appear in the Clinical Gastroenterology and Hepatology journal. In one study, researchers obtained fecal samples from 435 patients with newly diagnosed CRC, calculating sensitivities of a quantitative FIT at cutoffs recommended by the manufacturer and at alternative cutoffs for tumors at different stages. Tumors were stratified by location. They used Union for International Cancer Control (UICC) stage and T stage (infiltration) to measure sensitivity.

The FIT identified patients with CRC with overall high sensitivity but missed nearly 50% of small (T1) and 32% of UICC stage I CRCs. Sensitivity was particularly low for T1 and stage I cancers in the distal colon (32% and 52%, respectively) although generally very high for cancers with higher T stage (T2-T4) and more advanced stage (UICC stage II–IV) overall.

“Low sensitivity of FIT for early-stage CRC underlines the need for research on potential improvements in FIT-based CRC screening. Future studies should investigate determinants of false-negative FITs in different CRC stages,” Tobias Niedermaier, MPH, PhD, clinical epidemiology and aging research scientist at German Cancer Research Center and the study’s corresponding author, told CLN Stat.

According to editorialists Senore and Zorzi, the study sheds new light on the test’s sensitivity with respect to tumor characteristics. “These findings confirm the results of previous reports that showed that early stage CRCs and advanced adenomas are less likely to bleed than advanced-stage CRCs, as well as studies that reported that FIT sensitivity (especially for early-stage CRC or advanced adenomas) decreases with higher cutoff levels,” they summarized. 

A periodic FIT, however, might have some benefit in individuals with average CRC risk. Another study examined the merits of colonoscopy in patients with negative FIT tests in a large program that conducted annual screening.

Specifically, the investigators wanted to see if a colonoscopy identified any cancer missed by the FIT. The researchers identified 268 cases of CRC from a database search of 96,804 subjects ages 50–75 years with initial negative FIT results. They followed these individuals under four endpoints: initial colonoscopy, health plan disenrollment, death, or December 31, 2015, comparing them against a non-CRC control group.

In asymptomatic people without risk factors who had a negative FIT within 2 years, colonoscopy had a very small chance of finding CRC. In this cohort, the overall rate of cancer was 1.4 per 1,000. Just 0.7 per 1,000 subjects 50 to 59 years of age had cancer. “The rate increased with age, but the rates found at all ages are much lower than rates of cancer in people undergoing screening colonoscopy without a prior FIT,” lead authors George F. Longstreth, MD, and Daniel S. Anderson, MD, FACP, of Kaiser Permanente, Southern California, San Diego, told CLN Stat in a statement.

From these findings, they concluded that a periodic FIT was an accurate test in people with average CRC risk. “No test is 100% accurate, but colorectal cancer was so infrequent in our patients that we believe the term ‘accurate’ is appropriate,” clarified Longstreth and Anderson. FIT is the dominant screening test for colorectal cancer in most economically advanced countries, and the results support the accuracy of widespread periodic FIT screening, they added.

“The observed trend toward a reduction of the protective effect of FIT screening with increasing interval since the last negative test also is consistent with previous findings. These data therefore are providing additional evidence supporting the adoption of a 2-year interval for FIT screening,” wrote Senore and Zorzi.

Both studies focused on a single screening episode analysis, “which cannot account for the potential contribution of repeated FIT applications to overall screening effectiveness,” they added. To fully evaluate FIT sensitivity and effectiveness, a longitudinal study should assess its performance over several rounds of testing, “taking into account the stage and site distribution of screen-detected CRCs and [interval CRCs] ICs in each round,” they suggested. The study should also evaluate the location and detection rate of advanced adenomas and quantitative fecal hemoglobin results during the rounds of testing.