# Colorectal Cancer Risk With Negative Colonoscopy or Nonadherence After Positive FOBT Screening

## TL;DR

The study finds that people who get a negative colonoscopy after a positive fecal test have lower colorectal cancer risk, while those who skip follow-up colonoscopy have much higher risk.

## Contribution

The study introduces risk-based follow-up strategies for colorectal cancer screening based on colonoscopy outcomes and nonadherence.

## Key findings

- Negative colonoscopy results after a positive FOBT are linked to significantly lower CRC incidence.
- Nonadherence to follow-up colonoscopy after a positive FOBT is associated with a fourfold increase in CRC risk.
- Men showed a greater reduction in CRC risk after a negative colonoscopy compared to women.

## Abstract

This cohort study investigates the risk of colorectal cancer associated with a negative colonoscopy result or nonadherence to follow-up colonoscopy after a positive fecal occult blood test (FOBT) screening result.

What is the risk of colorectal cancer after a negative colonoscopy result or after nonadherence to follow-up colonoscopy among individuals with a positive result in a biennial fecal occult blood test screening?

In this cohort study of 14 873 individuals with a positive fecal occult blood test screening test, those with a negative screening colonoscopy result had a decreased colorectal cancer risk, while nonadherence to follow-up colonoscopy was associated with an increased risk compared with the general population.

These findings support risk-based follow-up strategies in colorectal cancer screening programs and highlight a high-risk group that may benefit from targeted interventions to improve early tumor detection.

Population-based colorectal cancer (CRC) screening programs are implemented globally. When determining screening intervals, variations in the risk of subsequent CRC by colonoscopy outcome should be considered.

To evaluate the incidence of CRC after a negative screening colonoscopy result or nonadherence to colonoscopy in individuals with a positive fecal occult blood test (FOBT) result.

This was a prospective cohort study conducted between January 1, 2008, and December 31, 2021. It was conducted within a population-based CRC screening program in the Stockholm-Gotland region, Sweden, using biennial FOBT as the primary screening test in the target population aged 60 to 69 years. The study cohort included all men and women born between 1938 and 1954 residing in the Stockholm-Gotland region between 2008 and 2012 who were invited to a CRC screening. All participants with a positive FOBT result were identified. Data provided by national registers were analyzed from October 2024 through January 2026.

Individuals with a positive FOBT result were categorized as (1) having a negative result on recommended follow-up colonoscopy or (2) nonadherence to recommended follow-up colonoscopy.

The primary outcome was CRC incidence compared with the general population (defined as all individuals in the cohort who were invited to screening, excluding those with negative colonoscopy or nonadherence following positive FOBT). This was measured by standardized incidence ratio (SIR).

Of 318 096 individuals invited to CRC screening with FOBT, 14 873 had a positive FOBT result (7799 male [52.4%]; median [IQR] age, 65 [63-67] years). Of these individuals, 11 473 (87.3%) underwent a colonoscopy, and 8433 of those colonoscopies (73.5%) were negative. Individuals with a negative screening colonoscopy result had a significantly lower observed CRC incidence (SIR, 0.52; 95% CI, 0.39-0.68) relative to the general population, with a lower SIR in men (0.37; 95% CI, 0.25-0.56) than women (0.71; 95% CI, 0.49-1.03). In contrast, individuals with a positive FOBT who did not adhere to follow-up colonoscopy had a markedly increased CRC incidence (SIR, 4.21; 95% CI, 3.24-5.48) compared with the general population.

In this study, a decrease in CRC incidence was observed among individuals with negative results in screening colonoscopies, with a greater decrease in men, supporting risk-based, individualized follow-up strategies. A high-risk group for CRC was identified among individuals who did not adhere to follow-up colonoscopy, enabling targeted interventions to improve early CRC detection.