Defining The Lifetime Endometrial Cancer Risk Threshold At Which Risk-Reducing Hysterectomy And The Levonorgestrel-Releasing Intrauterine System Are Cost-Effective

Abstract

Introduction/Background Risk-reducing hysterectomy (RRH) is currently offered to women with Lynch-Syndrome, where it is highly clinically and cost-effective at preventing endometrial cancer (EC). Although personalised EC risk-prediction tools are being developed, the management of increased EC-risk women outside Lynch-Syndrome is undefined. This study aims to determine the lifetime EC-risk (from any cause) at which RRH and the levonorgestrel-releasing intra-uterine system (IUS) are cost-effective. Methodology A Markov-model compared the cost-effectiveness of RRH and IUS against no prevention, among women aged 40-50 years at varying lifetime EC-risks from 3%-40%. This used quality-of-life data from the PRESCORES (ISRCTN17432105) study, published literature, a UK public healthcare payer-perspective and lifetime horizon. The incremental cost-effectiveness ratio (ICER) was calculated as the cost per quality-adjusted life-year (QALY) gained, using NICE willingness-to-pay thresholds of 20,000-30,000/QALY. Sensitivity and scenario analyses were performed, including for obesity. Results RRH was cost-effective for women aged 40 years with a lifetime EC-risk threshold of 17-21% (for a 30,000-20,000/QALY threshold), and from 50 years at an EC-risk threshold of 14-17%. Scenario analyses for obesity found these thresholds increased by 5-8% with BMI 35-40kg/m2 and 7-12% with BMI over 40kg/m2. The IUS was cost-effective for women aged 40 years at a lifetime EC -risk threshold of 6-7%, and from 50 years at an EC -risk threshold of 4-5%. These thresholds increased by 0-1% with BMI 35-40kg/m2 and 1-2% with BMI over 40kg/m2. At these risk levels, RRH and IUS resulted in increased costs, QALYs and life-years gained, and reduced EC cases and deaths, compared to no prevention. Conclusion We define for the first time the lifetime EC-risk threshold at which RRH and the IUS are cost-effective and may be offered for EC-prevention. This includes scenario analyses of obesity, the major non-genetic risk-factor. These findings are highly relevant to clinicians, researchers and policy-makers considering EC risk-reduction.