Noninvasive Stool DNA Testing May Outperform Colonoscopy Long-Term in Real-World CRC Screening

Repeated noninvasive stool DNA testing could offer greater real-world effectiveness than colonoscopy for colorectal cancer (CRC) screening over a 10-year period, largely due to higher patient adherence and cumulative screening benefits, according to a new modeling study in the Journal of Medical Economics.¹

Current guidelines recommend multiple screening options, including colonoscopy, the gold standard, every 10 years for people at average risk or multitarget stool DNA (mt-sDNA) testing every 3.

Next-generation mt-sDNA testing is a noninvasive, at-home option that detects DNA biomarkers and blood in stool associated with colorectal cancer and advanced precancerous lesions. Because it does not require preparation or procedural visits, it tends to achieve higher screening adherence in real-world settings. Use of this screening method has increased significantly, accounting for 0.4% in 2015 and jumping up significantly to account for 9% of screenings in 2018.²

“Because the effectiveness of CRC screening at the population level depends not only on test performance but also on adherence and feasibility of implementation, identifying strategies that perform well under real-world conditions is critical,” detailed the researchers.¹

To better understand how these differences play out over time, researchers used a validated microsimulation model to compare 3 rounds of next-generation mt-sDNA testing over 10 years versus a single colonoscopy. The model incorporated real-world adherence rates, test performance data, and disease progression patterns to estimate long-term outcomes.

The findings indicate that when real-world adherence is considered, next-generation mt-sDNA detected 13% more precancerous lesions and 11% more colorectal cancer cases compared with colonoscopy. Importantly, a much larger proportion of cancers were identified through proactive screening rather than after symptoms developed, suggesting earlier detection and intervention.

These differences translated into meaningful clinical outcomes. The model estimated a 33% reduction in CRC mortality with next-generation mt-sDNA screening, compared with a 20% reduction for colonoscopy. In addition, stool DNA testing was associated with 62% more life-years gained, highlighting its potential impact on long-term survival.

A key driver of these results is patient adherence, the researchers highlighted. In the study, adherence to stool DNA testing was estimated at 72%, compared with just 38% for colonoscopy. Because screening effectiveness depends not only on test accuracy but also on whether patients complete recommended screening at appropriate intervals, higher participation rates can significantly amplify real-world benefits.

Sensitivity analyses reinforced these findings. Even when adherence rates were varied, stool DNA testing consistently outperformed colonoscopy across multiple outcomes, including life-years gained and mortality reduction.

The researchers highlighted that colonoscopy would require substantially higher adherence than current levels to match the effectiveness of stool-based screening.

Notably, the gap between the 2 strategies narrowed under ideal conditions. In a scenario assuming perfect adherence for both tests, colonoscopy showed somewhat stronger mortality reduction, reflecting its high sensitivity and ability to remove lesions during the procedure.

The study also underscored broader system-level considerations. With more than 60 million US adults eligible for CRC screening and limited colonoscopy capacity, expanding access to noninvasive options could help alleviate resource constraints while increasing overall screening rates.

Despite its strengths, the study had limitations, the researchers wrote. As a modeling analysis, it relied on assumptions about adherence and disease progression that may not fully capture individual patient variability. It also focused on a 10-year time horizon rather than lifetime outcomes, and did not include cost-effectiveness analyses.

References

1. Dose M, Ebner DW, Vahdat V, et al. Model-based evaluation of colorectal cancer screening effectiveness: three rounds of multitarget stool DNA testing versus one colonoscopy. J Med Econ. 2026;29(1):986-993. doi:10.1080/13696998.2026.2645491

2. Kowalkowski H, Austin G, Guo Y, Miller-Wilson L-A, Byfield SD. Patterns of colorectal cancer screening and adherence rates among an average-risk population enrolled in a national health insurance provider during 2009–2018 in the United States. Prev Med Rep. 2023;36:102497. doi:10.1016/j.pmedr.2023.102497