Introduction
Colorectal cancer (CRC) remains a leading cause of cancer-related deaths in the U.S., with persistent disparities across racial and ethnic groups. Current uniform screening guidelines overlook population differences in risk. Polygenic risk scores (PRS) offer a pathway to personalized, risk-stratified screening, but their cost-effectiveness across diverse populations is unclear.
Aims & Methods
In this study, we estimated the cost-effectiveness of PRS-based, risk-stratified screening across four major U.S. racial and ethnic groups (White, Black, Asian and Hispanic), modelling lifetime costs, quality-adjusted life-years gained (QALYGs), and colonoscopy use to assess both overall and subgroup-specific outcomes.
PRS data from the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO) were used to stratify individuals into risk 40 groups. The microsimulation model MISCAN-Colon was used to determine the optimal colonoscopy screening strategy for each risk group within the racial and ethnic groups. Investigated strategies varied in terms of starting age (40–60 years), stopping age (70–85 years), and screening interval (5–15 years). Within each racial and ethnic group, the cost-effectiveness of the optimal strategies of the 40 risk groups was compared with uniform colonoscopy screening (ages 45–75, every 10 years).
Results
Risk-stratified screening produced different recommendations across risk levels and populations. For low-risk groups, strategies ranged from no screening in Whites and Blacks to a one-time colonoscopy at age 55 for Asians and at age 60 for Hispanics. In contrast, for high-risk groups, all populations benefited most from intensive screening with colonoscopy every 5 years from ages 40–85. Across all racial and ethnic groups, PRS-guided screening outperformed uniform strategies, preventing more CRC cases and deaths but at the cost of higher colonoscopy use and costs. In constrained analyses, when QALYGs were fixed to the level of uniform screening, risk-stratified screening reduced costs by 6–27% and when costs were fixed to the level of uniform screening QALYGs increased by 8–29% These efficiency gains were most pronounced in Hispanics (–27% costs; +29% QALYGs) and Asians (–14% costs; +13% QALYGs), with smaller but consistent improvements in Whites (-9% costs; +12% QALYGs) and Blacks (-6% costs; +8%QALYGs).
Table 1. Lifetime Effects and Costs per 1,000 40-Year-Old Individuals for No Screening, Uniform Screening, and PRS-Guided Risk-Stratified Screening at a $100,000/QALYG Threshold, With QALYGs- and Cost-Constrained Analyses, Stratified by Racial and Ethnic Group (Results only for Hispanics and Asians)
Asians
Strategy
| QALYGs
| Costs
| LYGs
| Colonoscopies
| CRC cases
| CRC deaths
|
|
Uniform
| 2936
| 113088
| 2297
| 69207
| 471
| 128 |
|
Risk-stratified WTP$100K
| 3841
| 137490
| 2962
| 136528
| 289
| 60 |
|
Constraining QALYGs WTP$30.8K
| 2934
| 99201
| 2263
| 69892
| 354
| 89 |
|
Constraining Costs WTP$40.3K
| 3329
| 112031
| 2568
| 99562
| 291
| 65 |
|
| Hispanics |
|
| Uniform | 2347
| 104423
| 1854
| 64953
| 402
| 109
|
|
Risk-stratified WTP$100K
| 3073
| 126058
| 2408
| 123137
| 253
| 52
|
|
Constraining QALYGs WTP$25.4K
| 2342
| 77087
| 1834
| 64845
| 309 | 78 |
|
Constraining Costs WTP$80.1K
| 3013
| 93895
| 2359
| 117402
| 256 | 54 |
|
Conclusion
PRS-guided screening may offer a pathway to more tailored CRC prevention, with modest overall gains but potentially greater cost savings and health benefits in Hispanics and Asians.
References
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3. Dixon P, Keeney E, Taylor JC, Wordsworth S, Martin RM. Can polygenic risk scores contribute to cost-effective cancer screening? A systematic review. Genet Med. 2022;24(8):1604-17.
4. Tamlander M, Jermy B, Seppälä TT, Färkkilä M, FinnGen, Widén E, et al. Genome-wide polygenic risk scores for colorectal cancer have implications for risk-based screening. Br J Cancer. 2024;130(4):651-9.
Disclosure
No conflicts of interest.