A fecal immunochemical test (FIT) conducted 2 years apart could form the basis for population-based colorectal cancer screening if this approach goes on to show a mortality benefit, according to a preliminary analysis.
Researchers are investigating the effect of this timeframe of FIT screening as well as a single colonoscopy on colorectal cancer incidence and mortality as the primary endpoints of a randomized controlled trial called SCREESCO. Both were compared to a control of no intervention.
“The rationale is to have the FIT test for a 2-year interval and then no more [colorectal cancer screening] after that,” Anna Forsberg, MD, PhD, lead author and a researcher at the Karolinska Institute in Stockholm, Sweden, told Medscape Medical News.
In addition to the spacing of the FIT screening, the cutoff value in the stool sample of 10 micrograms of hemoglobin per gram is also unique to SCREESCO.
“In most other studies, the cutoff is either 20 micrograms or 40 micrograms,” Forsberg said. “With this very low cutoff, we hope that we find cancer, including advanced adenomas that are precancerous and can be removed.”
The preliminary analysis reporting the trial’s baseline findings was published online March 14 in The Lancet Gastroenterology & Hepatology.
Comparing Two Interventions
Between 2014-2020, the study included 278,280 individuals, with 31,140 assigned to the colonoscopy group, 60,300 to the FIT group, and 186,840 to the control group. Both colonoscopy and FIT screening occurred at age 60 years.
Of the individuals in the colonoscopy group, 35.1% had a colonoscopy, compared with 55.5% in the FIT group who participated in at least one round of testing; 41.4% completed both rounds of FIT screening.
In the FIT group, 6.3% of the test results were positive, and 90.8% of individuals with a positive FIT test underwent a follow-up colonoscopy.
Polyps were found in 45.2% of colonoscopies in the colonoscopy group and in 58.2% in the FIT group. The median adenoma detection rate was 20% in the colonoscopy group and 34% in the FIT group.
The intention-to-treat analysis found a colorectal cancer detection rate of 0.16% in the colonoscopy group and 0.20% in the FIT group, but it was not statistically significant. Advanced adenomas were detected more often in the colonoscopy group than in the FIT group (2.05% vs 1.61%; relative risk, 1.27; 95% CI, 1.15 – 1.41).
The number of colonoscopies needed to detect one cancer was 218 in the colonoscopy group and 49 in the FIT group; to detect a single advanced adenoma, 17 and 6 colonoscopies had to be done, respectively.
Too Early to Change Screening Strategies
When asked to comment on the study, David Johnson, MD, professor of medicine and chief of gastroenterology at Eastern Virginia Medical School in Norfolk, said that the results should be understood as preliminary.
“This is only a description of what they have to date and not of what they proposed for their endpoints,” said Johnson, who wasn’t associated with the research. “A recommendation for changing screening strategies based on these findings would be very inappropriate at this point.”
Johnson raised concerns about the quality of the colonoscopies, noting that the procedures were carried out by a mix of gastroenterologists and surgeons. He also said that several measures, including the surprisingly low yields for the colonoscopy group and even more so for the FIT-positive group, were concerning.
“They are much lower than even the minimum standard that we would use as benchmark quality indicators in the United States,” he said. “That raises a considerable flag to me that that the quality of the colonoscopy confirmation [after a positive FIT test] and screening were both low.”
Johnson said the ultimate goal of colorectal cancer screening is to detect and remove polyps, a strategy that has been shown to reduce mortality. But FIT tests are not well suited to detecting adenomatous polyps and are of little value in detecting sessile serrated lesions.
“FIT is a detection for cancer, not a detection for polyps. The true value of screening is not just detection but prevention by identification and removal of precancerous polyps,” he said.
Still, Forsberg emphasized the importance of maximizing uptake of colorectal cancer screening.
“When we pooled the results from the two interventions, the participation in the FIT arm was 56%, which is good. If you look at international figures, that is also high for participation in colonoscopy screening,” Forsberg said.
“Participation is the main thing. You can have the most fantastic test, but if people don’t participate, then it’s not worth much.”
SCREESCO is one of several ongoing studies comparing screening strategies that employ colonoscopy or FIT. Other studies of colon cancer surveillance methods include the COLONPREV and CONFIRM trials comparing colonoscopy to FIT, and the NordICC trial comparing colonoscopy to no intervention. None of these trials have yet published their final results on colorectal cancer mortality.
Forsberg and Johnson have disclosed no relevant financial disclosures. The study was funded by Swedish regions, County Council, Regional Cancer Center Mellansverige, Swedish Cancer Society, Aleris Research and Development Fund, and Eiken Chemical.
Lancet Gastroenterol & Hepatol. Published online March 14, 2022. Abstract