Inviting adults aged 60 years for colorectal cancer screening moves diagnosis to an earlier stage without reducing short-term mortality, highlighting both the promise and trade-offs of population-based cancer detection.

study: Colonoscopy and fecal immunochemical testing versus usual care in colorectal cancer diagnostic screening: the SCREESCO randomized controlled trial. Image credit: Jo Panuwat D/Shutterstock.com

recent natural medicine The study conducted the large SCREESCO randomized trial to assess whether colorectal cancer (CRC) Screening at age 60 is done by primary colonoscopy or fecal immunochemistry (fit), provides greater benefit or harm than usual care for adults aged 60 years.

Variations in international colorectal cancer screening approaches

Many organizations, such as the American College of Gastroenterology and the European Society of Gastrointestinal Endoscopy, recommend CRC screening with colonoscopy or FIT for individuals aged 50 to 75 years. Although colonoscopy screening has been widely studied, there are few randomized trials comparing FIT to usual care. Although colonoscopies can cause serious adverse events, these remain rare and randomized evidence of screening-related benefits and harms compared with usual care is limited.

Colonoscopies are usually only offered to people who are at high risk, based on the results of a noninvasive test that shows a large amount of blood in the stool. In many countries, most people, especially those aged 50 to 75, are screened for colorectal cancer every two years using FIT.

Of note, there is considerable international variation in the cutoff values ​​used to define a positive FIT result, ranging from 8.5 μg of hemoglobin/g of stool to 120 μg/g of stool. This variation reflects differences in national health policies, population risk profiles, and health resources and can influence both the sensitivity and specificity of screening programs and the downstream demand for colonoscopies.

It is essential to quantify both the benefits and risks of colorectal cancer screening to guide health policy regarding early detection and removal of colorectal cancer and precancerous lesions.

SCREESCO trial design

SCREESCO Randomized Controlled Trial (RCT) in Sweden, designed to directly compare different approaches to detecting CRC. In this study, participants were randomly assigned to one of three groups: a primary colonoscopy screening group, a group that underwent two two-stool FIT screenings performed two years apart using a positivity threshold of 10 μg of hemoglobin per gram of feces in either sample to increase sensitivity, or a control group that continued with usual care and was not invited for screening. This design allowed researchers to evaluate the effectiveness and risks of both colonoscopy and FIT screening strategies in parallel with standard medical approaches.

In the Stockholm-Gotland region, biennial one-sample FIT screening has been offered for individuals aged 60 to 69 years since 2015 and for individuals aged 60 to 74 years from 2020, with cut-off values ​​of 40 μg/g for women and 80 μg/g for men. The nationwide rollout of this FIT-based program, applying the same criteria, will begin in 2021 and is targeted for completion by 2026.

The SCREESCO RCT used comprehensive national health registries to assess diagnostic rates, total number of diagnosed colorectal cancer cases, and adverse events in screening and control groups during the diagnostic phase (2014-2020) on an intention-to-screen basis with a median follow-up of approximately 4.8 years. The study also assessed whether randomization resulted in comparable groups at baseline, whether screening increased colorectal cancer detection, especially for early-stage (I-II) cancers, compared with usual care, and whether screening was associated with short-term side effects such as cardiovascular events, gastrointestinal events, and death from any cause.

Screening promotes early cancer detection without affecting overall mortality

The SCREESCO randomized trial enrolled more than 278,000 Swedish adults and randomly assigned them to receive colonoscopy, FIT, or no screening. Demographics and health history were well balanced between groups, and median follow-up was nearly 5 years. Participation rates varied between groups, with approximately 35% of patients invited for colonoscopy and 55% of patients invited for FIT completing at least one screening round, reflecting intent to screen.

Although screening with colonoscopy or FIT moved CRC diagnosis to an earlier stage, the absolute number of cancers detected remained small compared to the overall study population. The colonoscopy group had a 38% higher early colorectal cancer detection rate compared to controls, and the FIT group had a 19% increase. Conversely, late-stage colorectal cancer was less common among screened patients, with reductions observed in both screening groups and slightly more pronounced in the FIT group.

Despite this change in stage, the total number of colorectal cancer cases between groups remained similar during follow-up at this stage of diagnosis, indicating that screening may have accelerated the timing of cancer detection within the current follow-up period, rather than demonstrating an overall reduction in incidence. Longer follow-up is needed to determine whether screening ultimately prevents cancer or reduces mortality, and the possibility of some overdiagnosis cannot yet be ruled out.

Short-term risks existed, but were small. There was a small transient increase in gastrointestinal and cardiovascular events in both screening groups during the first year, but these differences decreased over time. Serious screening-related complications were rare, with a 0.2% incidence of colonoscopy-related serious adverse events. At the end of the follow-up period, the incidence of cardiovascular events was similar in each group, although the FIT group showed a slight increase in venous thromboembolism and gastrointestinal bleeding compared with the control group.

All-cause mortality was unaffected by screening, and mortality rates were nearly identical in all groups over the study period. The trial was not yet designed to assess colorectal cancer-specific mortality, which remains the primary endpoint with long-term follow-up planned. Men had a higher overall incidence of colorectal cancer and a higher incidence of advanced cancer than women, but they had similar rates of cardiovascular events and slightly less frequent gastrointestinal complications.

conclusion

Colonoscopy and FIT screening both detected more early colorectal cancers than usual care, but did not increase overall cancer incidence or reduce all-cause mortality during follow-up at the diagnosis stage. Gastrointestinal and cardiovascular event rates were higher in the first year after screening, but these differences decreased over time.

The benefits of detecting more early-stage cancers must be weighed against short-term increases in adverse events, and long-term follow-up is needed to determine the effect of screening on colorectal cancer mortality and overall cancer prevention.

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