By Deborah Borfitz
November 19, 2020 | In the U.K., it has become common practice to routinely screen people for colon cancer using a fecal immunochemical test (FIT) that measures the level of blood in the stool as opposed to going straight to a colonoscopy—long the gold standard in the U.S. Now, there is also convincing evidence that an FIT should be the first line of investigation for patients presenting with symptoms suspicious of colon cancer, the vast majority of whom don’t in fact have any serious problems, according to Muti Abulafi, consultant colorectal surgeon at Croydon University Hospital, a large hospital in south London.
FIT is almost 100% accurate at ruling out bowel cancer in patients with suspicious symptoms, concludes the largest international research study of its kind that recently published in Gut (DOI: 10.1136/gutjnl-2020-321956). Abulafi served as chief investigator for the NICE guidelines and Faecal Immunochemical Test (NICE FIT) study, which additionally found that the test reduces the number of referrals for colonoscopy by about 60% for patients with a negative FIT result.
Recruitment ran from October 2017 until April 2019, with 25,000 patients from 55 hospital sites in England invited to participate in the trial. Almost 10,000 patients with colonoscopy outcomes were included in the data analysis.
Identifying ways to reduce the number of unnecessary colonoscopies is imperative in England, where hospitals are fined if they fail to meet wait time targets, Abulafi notes. For routine colonoscopies, national guidance is that the wait should be no more than six weeks and, for urgent colonoscopies, 14 days. But if every symptomatic patient got referred to colonoscopy, the system would “literally break down.”
Physicians in the U.K. are paid a fixed salary by the National Health Service, so there is no incentive to grow procedural volume, says Abulafi. In the U.S., doctors (endoscopists, anesthesiologists, and pathologists) and facilities (hospitals and ambulatory surgery centers) are generally paid per procedure, a practice that has tended to favor the use of the most costly treatment options.
The latest study finding may further widen the utilization gap. Among symptomatic patients referred with suspected colorectal cancer symptoms, about 85% got a colonoscopy they likely didn’t need, says Abulafi. About 30% of those examined were “completely normal” and roughly half had benign conditions such as hemorrhoids, diverticulosis, or tiny insignificant polyps.
In England at least, one-quarter of bowel cancers present as advanced cases to the hospital emergency departments, Abulafi adds. There are several factors that explains this, possibly including fear of being immediately referred for a colonoscopy. More of them might have had their symptoms investigated sooner if they knew cancer would first be ruled out by a stool test.
FIT can exclude cancer with 99.8% certainty (when used at a cutoff at 2μg/g), meaning there is no need to refer anyone with a negative result, says Abulafi. They can be treated symptomatically in the first instance which, in the vast majority of cases, resolves the issue. If symptoms persist after four weeks they can then be sent to a colorectal surgeon or gastroenterologist for a colonoscopy.
Importantly, FIT as used in Europe gives a readout of how much blood is in the stool measured in microgram of hemoglobin per gram of feces (μg/g), not just whether it is above or below a specified threshold, Abulafi says. “We’ve found that the higher this number is the greater the likelihood of having cancer.” A reading of 1000μg/g, for example, indicates a 42% chance of cancer while a reading of 150μg/g puts the odds at about 31%. “This allows us to target who we should be scoping first.”
In Abulafi’s clinical opinion, FIT should be the first step for investigating symptomatic individuals. This excludes patients who have had bowel cancer in the past and are being monitored for recurrent disease, for which a CT scan and colonoscopy are the best tools for detecting as well as removing any detected growths.
The Better Option
Colorectal cancer is a priority concern in England in part because of the national guidance stipulating that patients with symptoms suspicious of colorectal cancer meeting national criteria be seen inside of two weeks and, if they’re diagnosed with cancer, have their treatment started within 62 days of the original referral or 31 days from diagnosis, says Abulafi. His research team is also interested in learning the diagnostic value of FIT for the other two serious bowel conditions—inflammatory bowel disease and high-risk adenoma—based on a forthcoming subgroup analysis of the dataset used in the newly published study.
To obtain the test, symptomatic patients visit their primary care physician for a consultation. If patients’ symptoms meet the national criteria, an FIT kit and instructions on how to collect a stool sample is given to them, he explains. They take the test at home and return the sample to the clinic for processing.
Abulafi says he expects that as FIT becomes more popular and more understood over the next few years it is likely to become available for purchase over the counter like a pregnancy test. The U.K. currently uses four systems for analyzing collected stool samples (HM-JACKarc, OC-Sensor, FOB-gold, and NS-Prime), depending on the procurement contract in the region, and his research team is in the process of doing a comparative study of those options.
In the U.S., the highly marketed Cologuard test also looks for cancer but by detecting DNA rather than blood in the stools. Interestingly, the sensitivity of Cologuard for colorectal cancer (as demonstrated in premarketing trials) is 92.3% overall—on par with colonoscopy—whereas FIT as practiced in Europe comes in at 97% (per the study in Gut) and is significantly less expensive than either of the other two options.
The first author of the NICE FIT study, Nigel D’Souza, was recognized for his work on the trial by the two main surgical societies in the U.K. D’Souza was honored earlier this year with the BJS Surgery Prize of The Association of Coloproctology of Great Britain and Ireland and the highly coveted Moynihan Prize of the Association of Surgery of Great Britain and Ireland. He helped Abulafi set up the study while doing his research fellowship at Croydon University Hospital.
When the pandemic hit the U.K. earlier this year, canceling and later disrupting cancer diagnostics services, clinicians in the London region began to rapidly implement the use of FIT in primary care in order to manage and triage patients with symptoms, Abulafi says.