A Trial-Based Cost-Utility Analysis of Metastasis-Directed Therapy for Oligorecurrent Prostate Cancer

Abstract

The optimal management of patients with oligorecurrent prostate cancer (PCa) is unknown. There is growing interest in metastasis-directed therapy (MDT) for this population. The objective was to assess cost-utility from a Belgian healthcare payer's perspective of MDT and delayed androgen deprivation therapy (ADT) in comparison with surveillance and delayed ADT, and with immediate ADT. A Markov decision-analytic trial-based model was developed, projecting the results over a 5-year time horizon with one-month cycles. Clinical data were derived from the STOMP trial and literature. Treatment costs were derived from official government documents. Probabilistic sensitivity analyses showed that MDT is cost-effective compared to surveillance (ICER: €8393/quality adjusted life year (QALY)) and immediate ADT (dominant strategy). The ICER is most sensitive to utilities in the different health states and the first month MDT cost. At a willingness-to-pay threshold of €40,000 per QALY, the cost of the first month MDT should not exceed €8136 to be cost-effective compared to surveillance. The Markov-model suggests that MDT for oligorecurrent PCa is potentially cost-effective in comparison with surveillance and delayed ADT, and in comparison with immediate ADT.

Keywords: cost-effective; cost-utility analysis; markov model; metastasis-directed therapy; oligometastasis; oligorecurrent; prostate cancer; prostatic neoplasms.

Figure A1

Cost-effectiveness acceptability curve of MDT versus surveillance. In order to evaluate the uncertainty of the input variables, the standard error of the mean was varied: mean * magnitude, with magnitude 0.05, 0.1, 0.15, 0.20, and 0.25. The results were robust, with MDT versus surveillance being cost-effective at a willingness-to-pay threshold of 40,000 euro in respectively 98%, 90.7%, 85.9%, 87.6%, and 86.2% of the iterations. MDT: Metastasis-directed therapy.

Figure 1

Probabilistic sensitivity analysis-cost-effectiveness acceptability curve. Please remark that the patients in the different groups (i.e., MDT, surveillance and ADT) entered different health states during follow-up and thus the corresponding costs and utilities of that health state were applied. Abbreviations CEAC: Cost-effectiveness acceptability curve; MDT: Metastasis-directed therapy.

Figure 2

Graphic representation of 10,000 simulations of the cost-utility analysis of MDT versus surveillance. Every dot represents a simulation of the cost-utility analysis. The red line represents the WTP threshold. The red dot represents the mean ICER. Differences are calculated as MDT minus surveillance/ADT. (A) Cost-utility plane of MDT versus surveillance. (B) Cost-utility plane of MDT versus ADT. Please remark the different scales in Figure 1A,B. Abbreviations; MDT: Metastasis-directed therapy; QALY: Quality adjusted life years; WTP: Willingness-to-pay.

Figure 3

Multiple cost-effectiveness acceptability curve. This curve shows the most cost-effective strategy depending on the willingness-to-pay threshold. Please remark that the patients in the different groups (i.e., MDT, surveillance and ADT) entered different health states during follow-up and thus the corresponding costs and utilities of that health state were applied. ADT: Androgen-deprivation therapy; MDT: Metastasis-directed therapy.

Figure 4

One-way sensitivity analysis—tornado diagram. Tornado model showing the impact of the different variables on the ICER. In this figure, all sensitivity scores were set at 100%. The figure depicts the impact on the ICER when the sensitivity score ranges from 80% to 120%. ADT: Androgen-deprivation therapy; MDT: Metastasis-directed therapy.

Figure 5

Scenario analyses. (A) Overall overview of the cost-utility of MDT versus surveillance or MDT versus ADT in function of the cost of MDT during the first month. (B) Overall overview of the cost-utility of MDT versus Surveillance or MDT versus ADT in function of the cost of MDT for SBRT. ADT: Androgen-deprivation therapy; ICER: Incremental cost-effectiveness ratio; MDT: Metastasis-directed therapy; SBRT: Stereotactic body radiotherapy.

Figure 6

Scenario analysis investigating ICER in function of the effect of MDT versus surveillance. 100% is the effect as it was observed in the STOMP trial (orange dot). As seen in the figure, the ICER becomes higher when the difference in the effect of MDT versus surveillance becomes smaller. ICER: Incremental cost-effectiveness ratio; MDT: Metastasis-directed therapy.

Figure 7

Markov model summarizing the state transitions (simplified model). Patients treated by MDT or surveillance enter the Markov model in the ADT-free state. Patients that are treated with immediate ADT enter the Markov model in the ADT state. Circles represents the different health states in the model. Arrows represent transitions between health states, Patients are at each health state at risk for developing side effects. ADT: Androgen-deprivation therapy; CRPC: Castration-resistant prostate cancer; MDT: Metastasis-directed therapy.