Cost-Effectiveness of Risk-Stratified Colorectal Cancer Screening Based on Polygenic Risk: Current Status and Future Potential

Abstract

Background Although uniform colonoscopy screening reduces colorectal cancer (CRC) mortality, risk-based screening may be more efficient. We investigated whether CRC screening based on polygenic risk is a cost-effective alternative to current uniform screening, and if not, under what conditions it would be. Methods The MISCAN-Colon model was used to simulate a hypothetical cohort of US 40-year-olds. Uniform screening was modeled as colonoscopy screening at ages 50, 60, and 70 years. For risk-stratified screening, individuals underwent polygenic testing with current and potential future discriminatory performance (area under the receiver-operating curve [AUC] of 0.60 and 0.65–0.80, respectively). Polygenic testing results were used to create risk groups, for which colonoscopy screening was optimized by varying the start age (40–60 years), end age (70–85 years), and interval (1–20 years). Results With current discriminatory performance, optimal screening ranged from once-only colonoscopy at age 60 years for the lowest-risk group to six colonoscopies at ages 40–80 years for the highest-risk group. While maintaining the same health benefits, risk-stratified screening increased costs by $59 per person. Risk-stratified screening could become cost-effective if the AUC value would increase beyond 0.65, the price per polygenic test would drop to less than $141, or risk-stratified screening would lead to a 5% increase in screening participation. Conclusions Currently, CRC screening based on polygenic risk is unlikely to be cost-effective compared with uniform screening. This is expected to change with a greater than 0.05 increase in AUC value, a greater than 30% reduction in polygenic testing costs, or a greater than 5% increase in adherence with screening.

Cost-effectiveness of polygenic risk profiling for primary open-angle glaucoma in the United Kingdom and Australia

“…Firstly, instead of repeating the screening tests every 3 or 5 years, the single largest cost in our proposed program is a one-off test for each participant and possibly to assess genetic risk for many other diseases. 49,50,51 Secondly, the PRS would determine a high-risk subpopulation who require regular follow-up, thereby reducing the population who require ongoing repeat screening costs. This would logically reduce the screening cost when compared with repeated IOP measurements, visual field tests and clinical examinations by trained personnel every few years.…”

A Genomic Test for Colorectal Cancer Risk: Is This Acceptable and Feasible in Primary Care?

“…This study explores the acceptability and feasibility of genomic testing for CRC risk within primary care, but there are of course other aspects of implementation, cost-effectiveness, and model selection that remain unanswered. Several cost-effectiveness analyses have shown that a risk-stratified CRC screening could be cost-effective with slight improvement in predictiveness of the genomic model, slight reduction in cost of the genomic test, or slight increase in subsequent screening adherence [21], and that it can reduce harms of a screening programme [47]. As the evidence for the predictiveness and cost-effectiveness of genomic risk prediction models for common conditions builds, as it rapidly continues to do, implementation studies must keep up.…”

“…Uptake of population iFOBT screening in Australia is only 41% [19], and it has been shown that endorsement by GPs could help increase screening rates [20]. A cost-effectiveness study of genomic testing to guide screening showed that increasing adherence to screening recommendations by 5% would make the genomic test cost-effective [21]. In this context, the use of a genomic test within primary care to guide the type and timing of CRC screening could improve the efficiency of population screening, by ensuring the right type of screening is recommended according to an individual’s risk and increasing adherence to those recommendations.…”

Precision Colorectal Cancer Screening with Polygenic Risk Score

“…Naber et al (50) optimized screening intervals for cost-efficiency and found that screening based on stratification with a baseline model with AUC of 0.6 would become cost-effective with PRS prices below 141 US dollars. Here, we have adapted their screening recommendations to a PRS model from Huyghe et al adapted and locally revalidated for individual (11).…”

“…Equivalent values for women are somewhat lower: 10.2% (9.33% -11.1%) and 1.6% (1.41% -2.6%). • Coloscopies every 10 years, ages 50 Next, we estimated the proportion of individuals with relative risks to an average individual in the Estonian population. We estimated that relative risks as more than 3.1, compared to an individual with median population PRS, in around 0.3% of females, between 1.6 and 3.1 in 11.9%, between 1.4 and 1.6 in 10.3%, between 0.9 and 1.4 in 37.7%, between 0.7 and 0.9 in 20.8%, between 0.6 and 0.7 in 9.4% and below 0.6 in 9.5%.…”