Cost-Effectiveness of Metastasis-Directed Therapy in Oligorecurrent Hormone-Sensitive Prostate Cancer

Abstract

Purpose: Oligorecurrent prostate cancer has historically been treated with indefinite androgen deprivation therapy (ADT), although many patients and providers opt to defer this treatment at the time of recurrence given quality-of-life and/or comorbidity considerations. Recently, metastasis-directed therapy (MDT) has emerged as a potential intermediary between surveillance and immediate continuous ADT. Simultaneously, advanced systemic therapy in addition to ADT has also been shown to improve survival in metastatic hormone-sensitive disease. This study aimed to compare the cost-effectiveness of treating oligorecurrent patients with upfront MDT before standard-of-care systemic therapy.

Methods and materials: A Markov-based cost-effectiveness analysis was constructed comparing 3 strategies: (1) upfront MDT → salvage abiraterone acetate plus prednisone (AAP) + ADT → salvage docetaxel + ADT; (2) upfront AAP + ADT → salvage docetaxel + ADT; and (3) upfront docetaxel + ADT → salvage AAP + ADT. Transition probabilities and utilities were derived from the literature. Using a 10-year time horizon and willingness-to-pay threshold of $100,000/quality-adjusted life year (QALY), net monetary benefit values were subsequently calculated for each treatment strategy.

Results: At 10 years, the base case revealed a total cost of $141,148, $166,807, and $136,154 with QALYs of 4.63, 4.89, and 4.00, respectively, reflecting a net monetary benefit of $322,240, $322,018, and $263,407 for upfront MDT, upfront AAP + ADT, and upfront docetaxel + ADT, respectively. In the probabilistic sensitivity analysis using a Monte Carlo simulation (1,000,000 simulations), upfront MDT was the cost-effective strategy in 53.6% of simulations. The probabilistic sensitivity analysis revealed 95% confidence intervals for cost ($75,914-$179,862, $124,431-$223,892, and $103,298-$180,617) and utility in QALYs (3.85-6.12, 3.91-5.86, and 3.02-5.22) for upfront MDT, upfront AAP + ADT, and upfront docetaxel + ADT, respectively.

Conclusions: At 10 years, upfront MDT followed by salvage AAP + ADT, is comparably cost-effective compared with upfront standard-of-care systemic therapy and may be considered a viable treatment strategy, especially in patients wishing to defer systemic therapy for quality-of-life or comorbidity concerns. Additional studies are needed to determine whether MDT causes a sustained meaningful delay in disease natural history and whether any benefit exists in combining MDT with upfront advanced systemic therapy.

Fig. 1.

Schema for Markov model comparing 3 treatment strategies in patients with low-volume oligorecurrent disease: (1) upfront metastasis-directed therapy followed by salvage abiraterone acetate plus prednisone (AAP) + androgen deprivation therapy (ADT) followed by salvage docetaxel + ADT, (2) upfront AAP + ADT followed by salvage docetaxel + ADT, and (3) upfront docetaxel + ADT followed by salvage AAP + ADT.

Fig. 2.

One-way sensitivity analyses reflecting effect of key model inputs on incremental net monetary benefit (NMB) of upfront metastasis-directed therapy versus upfront abiraterone acetate plus prednisone + androgen deprivation therapy (baseline comparator). Each key model input is shown with its lower/upper bounds in the sensitivity analysis and the corresponding effect on incremental NMB. The baseline expected value ($222) of incremental NMB is also shown.

Fig. 3.

Results from probabilistic sensitivity analysis using Monte Carlo simulation (1,000,000 simulations) to compare each of the 3 treatment strategies. The cost-effectiveness acceptability frontier is displayed on the left, showing the probability of each strategy being the most cost effective at varying willingness-to-pay thresholds. The cost-effectiveness scatterplot is presented on the right for individual simulations.