Benefits and harms of polygenic risk scores in organised cancer screening programmes: a cost-effectiveness analysis

While polygenic risk scores (PRS) could enable the streamlining of organised cancer screening programmes, its current discriminative ability is limited. We conducted a cost-effectiveness analysis to trade-off the benefits and harms of PRS-stratified cancer screening in China.

The validated National Cancer Center (NCC) modelling framework for six cancers (lung, liver, breast, gastric, colorectum, and oesophagus) was used to simulate cancer incidence, progression, stage-specific cancer detection, and risk of death. We estimated the number of cancer deaths averted, quality-adjusted life-years (QALY) gained, number needed to screen (NNS), overdiagnosis, and incremental cost-effectiveness ratio (ICER) of one-time PRS-stratified screening strategy (screening 25% of PRS-defined high-risk population) for a birth cohort at age 60 in 2025, compared with unstratified screening strategy (screening 25% of general population) and no screening strategy. We applied lifetime horizon, societal perspective, and 3% discount rate. An ICER less than $18,364 per QALY gained is considered cost-effective.

One-time cancer screening for population aged 60 was the most cost-effective strategy compared to screening at other ages. Compared with an unstratified screening strategy, the PRS-stratified screening strategy averted more cancer deaths (61,237 vs. 40,329), had a lower NNS to prevent one death (307 vs. 451), had a slightly higher overdiagnosis (14.1% vs. 13.8%), and associated with an additional 130,045 QALYs at an additional cost of $1942 million, over a lifetime horizon. The ICER for all six cancers combined was $14,930 per QALY gained, with the ICER varying from $7928 in colorectal cancer to $39,068 in liver cancer. ICER estimates were sensitive to changes in risk threshold and cost of PRS tools.

PRS-stratified screening strategy modestly improves clinical benefit and cost-effectiveness of organised cancer screening programmes. Reducing the costs of polygenic risk stratification is needed before PRS implementation.

The Chinese Academy of Medical Sciences, the Jing-jin-ji Special Projects for Basic Research Cooperation, and the Sanming Project of the Medicine in Shenzhen.