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A recent study found that patients who had a positive fecal occult blood test (FOBT) but didn’t follow through with a colonoscopy had a fourfold higher risk for colorectal cancer (CRC) than the general population. By contrast, patients who had positive FOBT who underwent colonoscopy and had a negative result had a considerably lower incidence of CRC than the general population.

“Individuals with a negative colonoscopy after a positive FOBT have a low subsequent CRC risk, suggesting that risk-adapted follow-up intervals may be appropriate within organized screening programs,” lead author Hanna Heyman, MD, general surgeon, Karolinska Institutet, Stockholm, Sweden, told Medscape Medical News.

On the other hand, “individuals who do not complete follow-up colonoscopy after a positive FOBT represent a high-risk group for CRC, highlighting the need for targeted efforts to improve colonoscopy adherence,” said Heyman, who is also a PhD candidate at Karolinska Institutet.

The study was published online in JAMA Network Open.

Filling a Knowledge Gap

Heyman explained the motivation behind conducting the study. “Screening intervals and follow-up recommendations vary substantially between countries, and there is limited evidence on long-term cancer risk after a negative colonoscopy in a strict FOBT-based screening setting,” she said. “We identified this as a knowledge gap and aimed to provide data that could help inform screening policies and improve follow-up strategies.”

The researchers prospectively studied 14,873 individuals with a positive FOBT test (52.4% men; mean [IQR] age, 65 years [63-67 years]), who engaged in a population-based CRC screening program from January 2008 to December 2021. They were categorized either as having a negative result on recommended follow-up colonoscopy or as being nonadherent with recommended follow-up colonoscopy.

The “general population” was defined as “all individuals in the cohort who were invited to screening, excluding those with negative colonoscopy or nonadherence following positive FOBT.”

In 2015, the fecal immunochemical test (FIT) replaced the earlier guaiac-based FOBT, and individuals who underwent FIT were included in the analysis, together with those who had undergone FOBT, although the researchers also compared the two tests.

Develop Targeted Strategies

Of individuals with a positive FOBT, 87.3% underwent colonoscopy; and of those, 73.5% had a significantly lower observed CRC incidence, relative to the general population (standardized incidence ratio [SIR], 0.52; 95% CI, 0.39-0.68). A greater decrease was found in men (SIR, 0.37; 95% CI, 0.25-0.56) than in women (SIR, 0.71; 95% CI, 0.49-1.03).

During follow-up, 52 CRC cases occurred in the negative colonoscopy group, with a higher percentage (55.8%) in women than in men. The median (range) time to CRC diagnosis was 4.8 (0.7-10.2) years, with a longer time to diagnosis in women than in men. The most common cancer stages were I and IV (30.8% and 26.9%, respectively).

By contrast, individuals with positive FOBT who did follow through on the colonoscopy recommendation had a “markedly increased” CRC incidence (SIR, 4.21; 95% CI, 3.24-5.48) compared with the general population. There were 56 CRC cases, with a shorter time to diagnosis (median, 2.8 [0.5-12.2] years) following FOBT screening. Here too, women had a longer time to diagnosis. Most cancers were stage III (30.4%).

SIRs were higher in those who had been screened with FIT vs FOBT (SIR, 7.60 [95% CI, 4.84-11.94] vs 3.43 [95% CI, 2.48-4.74]).

“Observed differences in [CRC] incidence suggest that a risk-based, individualized approach to follow-up may be beneficial,” the authors concluded. Factors to take into account, in addition to colonoscopy findings, should include FIT levels, age, and sex.

“Given limited colonoscopy resources and the expansion of screening programs to include broader and younger populations, it is essential for screening efforts to be efficient,” they added. “Resources should be allocated where they will have the greatest impact, and targeted strategies should be developed to engage high-risk individuals who do not attend follow-up procedures.”

One of the limitations noted by the authors is that the cohort included people screened both with FOBT and with FIT, which may impact generalizability because FIT “is now the standard method.”

Not a ‘Gray Area’

Commenting for Medscape Medical News, Cedrek McFadden, MD, clinical associate professor of surgery, University of South Carolina, Greenville, South Carolina, and Colorectal Cancer Alliance medical advisor, called it a “very important and practical study because it asks a question we see play out all the time in real life — what actually happens when patients never complete the follow-up colonoscopy?” The study “puts a spotlight on a group that’s easy to miss — patients who actually engaged with screening but never made it to the next step.”

McFadden continued: “What stood out to me is how clearly the risk stays elevated in those patients. A positive stool test without a diagnostic colonoscopy is not really a gray area. Those patients are still at substantially higher risk for colorectal cancer.”

This distinction matters, he emphasized. “Follow-up after stool-based screening is not just a box to check. It is really the point where screening either works or breaks down.”

On the other hand, “the study does not fully account for why patients didn’t complete the follow-up colonoscopy. That is a big part of the story,” McFadden noted. “In real life, nonadherence is rarely random. It is tied to access, cost, fear, health literacy, or just breakdowns in the system. If we do not understand those pieces, it is harder to turn these findings into real solutions.”

McFadden believes the study has several major take-home points for practicing clinicians. “A positive stool test is not the finish line. It is the start of the diagnostic process. If the follow-up colonoscopy does not happen, the benefit of screening is largely lost. This is not something we can be casual about.”

Additionally, “systems matter more than we sometimes admit. Good colorectal cancer prevention is not just about what happens in the procedure room. It is about navigation, follow-up, access, and removing the barriers that keep patients from completing colonoscopy after a positive test.”

He cautioned that the study “assumes a high-quality colonoscopy but that can vary. Bowel prep, adenoma detection rates, and whether the exam is complete all matter. A negative colonoscopy is not the same in every setting, and that changes how we interpret the risk.” He added that the study was conducted “in a specific screening program with its own structure and patient population. That may look different from what we see in the United States. So the message is strong, but we have to be thoughtful about how we apply it.”

The study was supported by grants from the Swedish Cancer Society, the Swedish Research Council, and Region Stockholm. Heyman disclosed having no relevant financial relationships. The other authors’ disclosures are listed on the original paper. McFadden disclosed having no relevant financial relationships.

Batya Swift Yasgur, MA, LSW, is a freelance writer with a counseling practice in Teaneck, New Jersey. She is a regular contributor to numerous medical publications, including Medscape and WebMD.