“As a result of limited resources, hospital endoscopy and colorectal services are  overwhelmed by the number of referrals from primary care of people with symptoms suspicious of bowel cancer,” explains Adam D. Gerrard, MBChB, MRCS. “Often these symptoms overlap with more common benign conditions, such as irritable bowel syndrome. Consequently, this delays the diagnosis of patients with colorectal cancer (CRC), while people without any pathology undergo invasive investigations.”

A better way of risk stratification, Dr. Gerrard points out, is needed to avoid unnecessary investigation and ensure a timely diagnosis for patients with significant bowel pathology. “Fecal immunochemical testing (FIT)—a noninvasive, inexpensive test performed at home—has been used for bowel screening since 2017 and as a rule-out test for patients with low-risk bowel symptoms,” he says. “It detects microscopic levels of human hemoglobin in fecal samples, producing a numeric value. Higher values are associated with more significant bowel pathology.”

The use of FIT in high-risk symptomatic patients suggestive of CRC would offer an objective means for risk assessment in patients, he adds, aiding clinicians in determining who needs urgent attention and who can be evaluated in primary care. “For patients most likely to have CRC or other significant bowel pathology, this would allow resources to be utilized more efficiently.”

Sensitivity of Single FIT Ranged From 85% to 90%

For a study published in the British Journal of Surgery, Dr. Gerrard and colleagues sought to define the diagnostic performance of a single FIT compared with double FIT in symptomatic populations.

Two sequential prospective patient cohorts were studied. In total, 2,260 patients in the single-FIT cohort completed a FIT and an investigation. In the subsequent double-FIT cohort, 3,426 patients completed at least one FIT and had an investigation, whereas 2,637 patients completed two FITs and an investigation.

“We initially studied single-FIT as this was used in the current bowel screening program for low-risk, symptomatic patients and was the method being used in other similar studies being conducted concomitantly,” Dr. Gerrard says. “Our results from this first cohort of single testing were in line with what other study groups were finding: FIT outperformed symptoms identifying patients most at risk for CRC. However, sensitivity ranged from 85% to 90%, meaning that 1 in 10 cancers were not identified.”

The study team wanted to see if they could increase the detection of CRC and other significant bowel pathology by conducting a second sequential double-FIT a few days apart. “Our rationale for this was that some lesions may bleed intermittently and therefore, might be identified by a second test,” Dr. Gerrard points out.

Performing a Double-FIT Proved Acceptable

The study revealed that performing a double-FIT was effective. “About 16% of patients had discordant results (one positive and one negative, or vice versa) and this occurred both with and without significant bowel pathology,” Dr. Gerrard says. “A total of 50% of CRC and 30% of significant bowel pathology missed by the first test were identified by the second test. Furthermore, those with two positive tests had the greatest risk for pathology and were identified for prioritization.”

The researchers also found that a model of the proposed double-FIT pathway showed that 69% of all patients referred to secondary care may not require urgent investigation (Figure).

Dr. Gerrard and colleagues agree that a double-FIT strategy can help detect cases of CRC and other significant bowel pathologies that would be missed with one FIT and would also allow greater prioritization of resources. “Both will hopefully contribute to earlier diagnosis, which is key to CRC staging, treatment options, and long-term survival,” Dr. Gerrard says.

Dr. Gerrard and colleagues envision a successful clinical impact of using FIT as being able to risk stratify and prioritize while generating reduced endoscopy demand, so that these cases can be addressed quickly.