Inviting adults to colon cancer screening at age 60 shifts diagnoses to earlier stages without reducing short-term mortality rates, highlighting both the promise and trade-offs of population-based cancer screening.
Study: Colonoscopy and faecal immunohistochemistry versus usual care in the diagnostic screening of colorectal cancer: the SCREESCO randomized controlled trial. Image credit: Jo Panuwat D/Shutterstock.com
A recent one Nature Medicine study conducted a large-scale SCREESCO randomized trial to assess whether colon cancer (CRC) screening at age 60, administered through primary colonoscopy or stool immunoassay (SUITABLE), provides greater benefits or harms than usual care in adults aged 60 years.
Variability in International CRC Screening Approaches
Many organizations, including the American College of Gastroenterology and the European Society for Gastrointestinal Endoscopy, recommend CRC screening for people aged 50–75 years, either by colonoscopy or FIT. While colonoscopy screening has been widely studied, few randomized trials have compared FIT with usual care. Although colonoscopy can cause serious side effects, these remain rare, and randomized evidence on the benefits and harms associated with screening compared with usual care is limited.
Colonoscopy is usually only offered to people at higher risk, based on results from non-invasive tests that show more blood in the stool. In many countries, most people are screened for CRC using FIT every 2 years, especially those aged 50–75 years.
In particular, there is considerable international variability in the cut-off values ​​used to define a positive FIT result, ranging from 8.5 µg of hemoglobin per gram of stool to 120 µg/g. This variability reflects differences in national health policy, population risk profiles, and health care resources, and may affect both the sensitivity and specificity of screening programs and the downstream demand for colonoscopy.
In order to guide health policy regarding the early detection and removal of CRC and precancerous lesions, it is necessary to quantify both the benefits and risks of CRC screening.
The SCREESCO trial design
The SCREESCO randomized controlled trial (RCT) in Sweden was designed to directly compare different approaches to CRC detection. In this trial, participants were randomly assigned to one of three groups: a primary screening colonoscopy group, a group that received two rounds of FIT screening with two stools performed 2 years apart, using a positivity threshold of 10 μg of hemoglobin per gram of stool in each sample to increase sensitivity, or a control group that did not continue to be invited to us. This design allowed the researchers to assess the effectiveness and risks of both colonoscopy and FIT screening strategies alongside the standard health care approach.
Biennial single-sample FIT screening is offered in the Stockholm-Gotland region from 2015 for people aged 60–69 and from 2020 for people aged 60–74, with thresholds of 40 µg/g for women and 80 µg/g for men. Nationwide implementation of this FIT-based program, applying the same criteria, began in 2021 and aims to be completed by 2026.
Using comprehensive national health registries, the SCREESCO RCT assessed diagnostic yield, total CRC cases diagnosed, and adverse events in the screening and control groups during the diagnostic phase (2014–2020), with a median follow-up of approximately 4.8 years, based on intention to screen. The study also evaluated whether randomization produced comparable groups at baseline, whether screening increased CRC detection, particularly for early-stage (I-II) cancer, compared with usual care, and whether screening was associated with short-term adverse events, including cardiovascular and gastrointestinal events and death from any cause.
Screening enhances early stage cancer detection without affecting overall mortality
The SCREESCO randomized trial enrolled more than 278,000 Swedish adults and randomly assigned them to colonoscopy, FIT, or no screening groups. Demographics and health history were balanced between groups, and the median follow-up time was nearly five years. Participation rates differed between groups: approximately 35% of those invited to colonoscopy and 55% of those invited to FIT completed at least one round of screening, reflecting the intention-to-screen design.
Colonoscopy or FIT screening shifted CRC diagnoses toward earlier stages, although the absolute number of cancers detected remained small relative to the total population studied. The colonoscopy group had a 38% higher early-stage CRC detection rate compared to controls, and the FIT group had a 19% increase. In contrast, end-stage CRCs were less common among those screened, with reductions seen in both screening arms and somewhat more pronounced in the FIT group.
Despite this stage shift, the total number of CRC cases between groups remained similar during this diagnostic phase follow-up, indicating that screening may have advanced the timing of cancer detection within the current follow-up window rather than demonstrating a reduction in overall incidence. Longer follow-up is needed to determine whether screening ultimately prevents cancers or reduces mortality, and the possibility of some overdiagnosis cannot yet be ruled out.
Short-term risks were present but modest. Both screening arms showed a slight temporary increase in gastrointestinal and cardiovascular events during the first year, but these differences decreased over time. Serious complications related to screening were rare, with a rate of 0.2% of colonoscopy-related major adverse events. At the end of the follow-up period, cardiovascular event rates were similar between groups, although the FIT arm showed a modest increase in venous thromboembolism and gastrointestinal bleeding compared with controls.
All-cause mortality was not affected by screening, and mortality rates were almost identical in all arms during the study period. The trial was not yet designed to assess colorectal cancer-related mortality, which remains a primary endpoint planned for long-term follow-up. Men had a higher overall incidence of CRC and more advanced cancers than women, although rates of cardiovascular events were similar and gastrointestinal complications were somewhat less common in men.
conclusions
Both colonoscopy and FIT screening detected more early-stage colon cancers than usual care, without an increase in overall cancer incidence during diagnostic phase follow-up or a reduction in all-cause mortality. Although rates of gastrointestinal and cardiovascular events were higher in the first year after screening, these differences decreased over time.
The benefit of finding more early-stage cancers must be weighed against the short-term increase in adverse effects, and long-term follow-up will be needed to determine the effect of screening on colorectal cancer mortality and overall cancer prevention.
