Risk-Adapted Screening Offers Viable Alternative for Colorectal Cancer

Colorectal cancer (CRC) screening remains a cornerstone of preventive care, yet balancing diagnostic yield with resource allocation and patient adherence continues to challenge health systems. While colonoscopy is the gold standard, its widespread application is often limited by cost and patient reluctance.

But a recent population-based randomized controlled trial (TARGET-C), published in Military Medical Research, evaluated whether a risk-adapted approach could optimize screening efficiency without compromising detection rates.

Comparing Screening Strategies

The trial enrolled 19,582 participants aged 50 to 74 years across six centers in China. Participants were randomized into three screening arms: one-time colonoscopy (3,883 participants), annual fecal immunochemical test (FIT) (7,793 participants), and a risk-adapted screening group (7,697 participants).

In the risk-adapted arm, individuals were stratified using a composite risk score based on age, sex, family history of CRC, smoking status, and body mass index. High-risk individuals were referred for colonoscopy, while low-risk participants received FIT.

Diagnostic Yield and Resource Utilization

Over four screening rounds, the cumulative detection rates for advanced neoplasms (CRC and advanced adenoma) were comparable across the three strategies:

• 2.8% in the colonoscopy arm (95% CI, 2.3–3.3)
• 2.6% in the risk-adapted arm (95% CI, 2.3–3.0)
• 2.3% in the FIT arm (95% CI, 2.0–2.6)

After adjusting for age, sex, and study center, the differences in detection rates were not statistically significant. The odds ratio for colonoscopy versus risk-adapted screening was 1.06 (95% CI, 0.83–1.34; P=0.658), and for risk-adapted screening versus FIT, it was 1.15 (95% CI, 0.93–1.41; P=0.197).

From a societal perspective, the cost to detect one advanced neoplasm was lowest in the colonoscopy group (15,341 Chinese Yuan), followed by the FIT group (21,754 Chinese Yuan), and highest in the risk-adapted group (24,300 Chinese Yuan).

However, long-term modeling over 15 years projected that risk-adapted screening could reduce CRC incidence by 16.7% and mortality by 21.5% compared with no screening. While slightly less effective than universal colonoscopy (which projected reductions of 24.6% and 24.8%, respectively), the risk-adapted approach required significantly fewer colonoscopies.

Real-World Adherence and Limitations

This study highlights the critical role of patient adherence in screening efficacy. Modeling suggested that under perfect adherence, risk-adapted screening would become the most cost-effective option. However, under observed real-world adherence, colonoscopy was the most cost-effective strategy.

Now, it’s important to consider several key limitations. Participation in colonoscopy and compliance with diagnostic follow-up among FIT-positive individuals were suboptimal, particularly among older participants with comorbidities. Additionally, in the risk-adapted arm, high-risk individuals who declined colonoscopy were not offered alternative screening modalities per protocol, which may have impacted overall detection rates. The lack of re-invitations for colonoscopy in the one-time screening arm also prevented direct comparisons of longitudinal participation dynamics.

A Complementary Approach for Resource-Constrained Settings

Even with these limitations in mind, these findings suggest that risk-adapted screening is a viable and effective strategy for CRC prevention. By stratifying patients based on clinical risk factors, healthcare providers can direct resource-intensive procedures like colonoscopy to those most likely to benefit, while offering less invasive options to lower-risk individuals.

And as diagnostic pathways evolve, risk-adapted screening could serve as a valuable complementary approach to established strategies, particularly in settings where endoscopic resources are limited.

Reference:
Chen HD, Lu B, Shi JF, et al. Effectiveness and cost-effectiveness of risk-adapted colorectal cancer screening: a randomized controlled trial and modeling analysis. Mil Med Res. 2025;12(1):82. Published 2025 Nov 24. doi:10.1186/s40779-025-00671-7