research and innovation programme (grant agreement number 634570) during the conduct of the study; Ms. Gogollari was partly funded by the Erasmus-Western Balkans mobility programme (ERAWEB), a project funded by the European Commission.

Objectives Benefit and cost effectiveness of breast cancer screening are still matters of controversy. Risk-adapted strategies are proposed to improve its benefit-harm and cost-benefit relations. Our objective was to perform a systematic review on economic breast cancer models evaluating primary and secondary prevention strategies in the European health care setting, with specific focus on model results, model characteristics, and risk-adapted strategies. Methods Literature databases were systematically searched for economic breast cancer models evaluating the cost effectiveness of breast cancer screening and prevention strategies in the European health care context. Characteristics, methodological details and results of the identified studies are reported in evidence tables. Economic model outputs are standardized to achieve comparable costeffectiveness ratios. Results Thirty-two economic evaluations of breast cancer screening and seven evaluations of primary breast cancer prevention were included. Five screening studies and none of the prevention studies considered risk-adapted strategies. Studies differed in methodologic features. Only about half of the screening studies modeled overdiagnosis-related harms, most often indirectly and without reporting their magnitude. All models predict gains in life expectancy and/or quality-adjusted life expectancy at acceptable costs. However, risk-adapted screening was shown to be more effective and efficient than conventional screening. Conclusions Economic models suggest that breast cancer screening and prevention are cost effective in the European setting. All screening models predict gains in life expectancy, which has not yet been confirmed by trials. European modelsrisk-adapted screening strategies are rare, but suggest that risk-adapted screening is more effective and efficient than conventional screening. Keywords breast cancer screening; breast cancer prevention; cost effectiveness; decision analysis; risk stratification; overdiagnosisDutch MISCAN model. State-transition models were used by six studies [63,46,57,39,65,61] and mathematical models (e.g., equation-or regression-based models) were used in five studies [35,51,62,58,55]. The remaining studies used other types of models, including two decision trees [53,54], two life-table models [40,41],and two mixed models combining different model types [45,38].Thirteen models can be classified as population models considering the actual age 9 structure of the local target population. All but five models considered a lifetime-time horizon, appropriate to account for the long-term consequences of screening. More than half of the screening studies (18/32) and two thirds (14/21) of the screening studies, including strategies comparable to currently established breast cancer screening programs, performed a cost-utility analysis, which is the type of analysis required to account for all kinds of non-fatal health consequences, including most harms caused by overdiagnosis-and overtreatment. Sixteen studies, including 12 with...

Endometrial cancer is the most common female genital tract cancer in developed countries. We systematically reviewed the current health-economic evidence on early detection and prevention strategies for endometrial cancer based on a search in relevant databases (Medline/Embase/Cochrane Library/CRD/EconLit). Study characteristics and results including life-years gained (LYG), quality-adjusted life-years (QALY) gained, and incremental cost-effectiveness ratios (ICERs) were summarized in standardized evidence tables. Economic results were transformed into 2019 euros using standard conversion methods (GDP-PPP, CPI). Seven studies were included, evaluating (1) screening for endometrial cancer in women with different risk profiles, (2) risk-reducing interventions for women at increased or high risk for endometrial cancer, and (3) genetic testing for germline mutations followed by risk-reducing interventions for diagnosed mutation carriers. Compared to no screening, screening with transvaginal sonography (TVS), biomarker CA-125, and endometrial biopsy yielded an ICER of 43,600 EUR/LYG (95,800 EUR/QALY) in women with Lynch syndrome at high endometrial cancer risk. For women considering prophylactic surgery, surgery was more effective and less costly than screening. In obese women, prevention using Levonorgestrel as of age 30 for five years had an ICER of 72,000 EUR/LYG; the ICER for using oral contraceptives for five years as of age 50 was 450,000 EUR/LYG. Genetic testing for mutations in women at increased risk for carrying a mutation followed by risk-reducing surgery yielded ICERs below 40,000 EUR/QALY. Based on study results, preventive surgery in mutation carriers and genetic testing in women at increased risk for mutations are cost-effective. Except for high-risk women, screening using TVS and endometrial biopsy is not cost-effective and may lead to overtreatment. Model-based analyses indicate that future biomarker screening in women at increased risk for cancer may be cost-effective, dependent on high test accuracy and moderate test costs. Future research should reveal risk-adapted early detection and prevention strategies for endometrial cancer.

<p>Results of cost-effectiveness studies evaluating risk-reducing intervention strategies in women with different risk profiles: discounted cost, life years (LY), quality-adjusted life years (QALY), incremental cost-effectiveness ratio (ICER) and incremental cost-utility ratio (ICUR).</p>

<p>Results of cost-effectiveness studies evaluating ovarian cancer screening strategies: discounted cost, life years (LY), quality-adjusted life years (QALY), incremental cost-effectiveness ratio (ICER) and incremental cost-utility ratio (ICUR).</p>