Cost-utility-analysis of molecular-integrated-profile for women with (high)intermediate risk endometrial cancer − PORTEC-4a an international, randomised, phase 3 trial

PURPOSE: The international PORTEC-4a trial demonstrated that individualised adjuvant treatment for women with (high)intermediate risk endometrial cancer (HIR-EC), guided by a molecular-integrated-risk-profile, achieves similar high local tumour control, while nearly half of patients were spared adjuvant treatment. Although determination of the molecular-integrated-profile increases diagnostics costs due to additional immunohistochemistry and DNA-sequencing, these costs may be offset by savings on other care and improved patient outcomes. PATIENTS AND METHODS: Women with early-stage HIR-EC eligible for the PORTEC-4a trial, were randomised (2:1) to either adjuvant treatment according to their molecular-integrated-profile or standard vaginal brachytherapy (VBT). EC-related costs were evaluated from a healthcare perspective over a three-year follow-up period. Costs were related to quality-adjusted-life-years (QALYs) using the EORTC-QLU-C10D instrument. T-test compared mean QALYs and costs, with multiple imputation for missing data. RESULTS: All 564 patients were included in the cost-utility-analysis; 367 in molecular-profile arm and 197 in standard arm. QALYs were comparable (p = 0.58). Total healthcare costs were somewhat, but not significantly, lower in molecular-profile arm compared to standard arm (€11,898 vs €13,047, p = 0.11). Costs spent up until recurrence were significantly lower in molecular-profile arm (€9,995 vs €11,926, p < 0.01), while there was no significant difference in treatment for recurrence (€1,903 vs €1,121, p = 0.17). At a willingness-to-pay threshold of €20,000/QALY, the strategy as proposed by PORTEC-4a was 89% likely to be cost-effective. CONCLUSION: Individualised adjuvant treatment based on a molecular-integrated-profile was more cost-effective than standard VBT for patients with HIR-EC. These results further support the implementation of the molecular-integrated-profile in routine clinical practice.