In the Journals

Tailoring FIT positivity threshold by age, sex may maximize colorectal cancer screening

Kevin Selby 2018
Kevin Selby

At the conventional fecal immunochemical test positivity threshold, programmatic sensitivity for detection of colorectal cancer decreased as age increased and was higher in men than women, according to data published in Annals of Internal Medicine.

“The positivity threshold, or the point at which FIT are designated as positive and screening participants get a colonoscopy, can be varied,” Kevin Selby, MD, MAS, from Kaiser Permanente Northern California, told Healio Internal Medicine. “Screening programs around the world actually use very different thresholds.”

“However, studies to date comparing thresholds have been relatively small, about 50 to 100 cancers,” he added. “That’s made it difficult to compare the benefits of lower thresholds (additional cancer detection) to the benefits of higher thresholds (fewer positive tests = fewer colonoscopies = fewer resources and fewer colonoscopy complications). Plus, the smaller studies couldn't compare patient subgroups, like between men and women, or age groups.”

Selby and colleagues performed a retrospective cohort study to measure the programmatic performance and sensitivity of FIT for colorectal cancer, as well as its quantitative hemoglobin positivity thresholds in a screening program.

The researchers studied 640,859 adults aged between 50 and 75 years who completed a baseline FIT and were followed for 2 years. During follow-up, three-quarters of participants had at least one additional FIT and 0.19% received a colorectal cancer diagnosis.

The programmatic sensitivity for cancer detection increased as positivity thresholds decreased, from 66% at 30 g/g to 74.3% at 20 g/g and 79.3% at 10 g/g. Similarly, there was an increase in the number of positive test results per cancer case detected, from 43 at 30 g/g to 52 at 20 g/g and 85 at 10 g/g.

The researchers found that if the positivity threshold was reduced from 20 g/g to 15 g/g, 3% more cancer cases would be detected, but would require 23% more colonoscopies.

When the FIT threshold was at its conventional level (20 g/g), programmatic sensitivity decreased as age increased from 79% for ages 50 to 59 years, to 73.4% for ages 60 to 69 years and 68.9% for ages 70 to 75 years. Additionally, programmatic sensitivity was higher in men than women (77% vs. 70.6%).

“We were surprised to find important differences in FIT accuracy between by age and sex,” Selby said. “At all thresholds, FIT is more sensitive in men than women and sensitivity declines with age. However, it’s important to stress that annual FIT tests remain one of the best ways to screen for colorectal cancer.”

“Going forward, we might want to have different screening recommendations for different segments of the population,” he added.

Selby noted that they were not able to quantify the impact of varying thresholds on advanced adenoma detection, but are working on a systematic review to address that information.

Douglas Corley 2018
Douglas A. Corley

“Screening programs should use these results to decide what positivity threshold is best for their screening participants,” Douglas A. Corley, MD, PhD, coauthor of the study also from Kaiser Permanente Northern California, told Healio Internal Medicine. “If they have enough colonoscopy capacity, they will want to use a threshold of 20 micrograms per gram or lower. Such is generally the situation in the United States. In other places, especially where inadequate colonoscopy resources are preventing population-level screening, higher thresholds should be used.”

In an accompanying editorial, Stephen P. Halloran, MBE, MSc, from the University of Surrey, England, wrote that the findings of Selby and colleagues support optimizing the rate of cancer detection within the context of constrained endoscopy resources.

However, “prevention through adenoma detection, as well as cost-effectiveness, also must be considered,” he wrote. – by Alaina Tedesco

Disclosures: Halloran reports no relevant financial disclosures. Selby reports receiving grants from the Swiss Cancer Research Foundation. Please see study for all other authors’ relevant financial disclosures.

Kevin Selby 2018
Kevin Selby

At the conventional fecal immunochemical test positivity threshold, programmatic sensitivity for detection of colorectal cancer decreased as age increased and was higher in men than women, according to data published in Annals of Internal Medicine.

“The positivity threshold, or the point at which FIT are designated as positive and screening participants get a colonoscopy, can be varied,” Kevin Selby, MD, MAS, from Kaiser Permanente Northern California, told Healio Internal Medicine. “Screening programs around the world actually use very different thresholds.”

“However, studies to date comparing thresholds have been relatively small, about 50 to 100 cancers,” he added. “That’s made it difficult to compare the benefits of lower thresholds (additional cancer detection) to the benefits of higher thresholds (fewer positive tests = fewer colonoscopies = fewer resources and fewer colonoscopy complications). Plus, the smaller studies couldn't compare patient subgroups, like between men and women, or age groups.”

Selby and colleagues performed a retrospective cohort study to measure the programmatic performance and sensitivity of FIT for colorectal cancer, as well as its quantitative hemoglobin positivity thresholds in a screening program.

The researchers studied 640,859 adults aged between 50 and 75 years who completed a baseline FIT and were followed for 2 years. During follow-up, three-quarters of participants had at least one additional FIT and 0.19% received a colorectal cancer diagnosis.

The programmatic sensitivity for cancer detection increased as positivity thresholds decreased, from 66% at 30 g/g to 74.3% at 20 g/g and 79.3% at 10 g/g. Similarly, there was an increase in the number of positive test results per cancer case detected, from 43 at 30 g/g to 52 at 20 g/g and 85 at 10 g/g.

The researchers found that if the positivity threshold was reduced from 20 g/g to 15 g/g, 3% more cancer cases would be detected, but would require 23% more colonoscopies.

When the FIT threshold was at its conventional level (20 g/g), programmatic sensitivity decreased as age increased from 79% for ages 50 to 59 years, to 73.4% for ages 60 to 69 years and 68.9% for ages 70 to 75 years. Additionally, programmatic sensitivity was higher in men than women (77% vs. 70.6%).

“We were surprised to find important differences in FIT accuracy between by age and sex,” Selby said. “At all thresholds, FIT is more sensitive in men than women and sensitivity declines with age. However, it’s important to stress that annual FIT tests remain one of the best ways to screen for colorectal cancer.”

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“Going forward, we might want to have different screening recommendations for different segments of the population,” he added.

Selby noted that they were not able to quantify the impact of varying thresholds on advanced adenoma detection, but are working on a systematic review to address that information.

Douglas Corley 2018
Douglas A. Corley

“Screening programs should use these results to decide what positivity threshold is best for their screening participants,” Douglas A. Corley, MD, PhD, coauthor of the study also from Kaiser Permanente Northern California, told Healio Internal Medicine. “If they have enough colonoscopy capacity, they will want to use a threshold of 20 micrograms per gram or lower. Such is generally the situation in the United States. In other places, especially where inadequate colonoscopy resources are preventing population-level screening, higher thresholds should be used.”

In an accompanying editorial, Stephen P. Halloran, MBE, MSc, from the University of Surrey, England, wrote that the findings of Selby and colleagues support optimizing the rate of cancer detection within the context of constrained endoscopy resources.

However, “prevention through adenoma detection, as well as cost-effectiveness, also must be considered,” he wrote. – by Alaina Tedesco

Disclosures: Halloran reports no relevant financial disclosures. Selby reports receiving grants from the Swiss Cancer Research Foundation. Please see study for all other authors’ relevant financial disclosures.