Department of Radiation Oncology, University of California Los Angeles, Los Angeles, California.
Department of Radiation Oncology, University of California Los Angeles, Los Angeles, California; VA Greater Los Angeles Health System, Los Angeles, California; Department of Urology, University of California Los Angeles, Los Angeles, California.
Int J Radiat Oncol Biol Phys. 2020 Nov 15;108(4):917-926. doi: 10.1016/j.ijrobp.2020.06.009. Epub 2020 Jun 13.
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.
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.
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.
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.
历史上,寡转移性前列腺癌一直采用无限期雄激素剥夺疗法(ADT)治疗,尽管许多患者和医生出于生活质量和/或合并症考虑,在复发时选择推迟这种治疗。最近,转移性定向治疗(MDT)已成为介于监测和立即连续 ADT 之间的潜在中间治疗方法。同时,除 ADT 以外的高级系统治疗也已显示可改善转移性激素敏感疾病的生存。本研究旨在比较在标准治疗系统治疗之前采用初始 MDT 治疗寡转移性患者的成本效益。
构建了一个基于马尔可夫的成本效益分析,比较了 3 种策略:(1)初始 MDT→挽救性阿比特龙醋酸酯+泼尼松(AAP)+ADT→挽救性多西他赛+ADT;(2)初始 AAP+ADT→挽救性多西他赛+ADT;和(3)初始多西他赛+ADT→挽救性 AAP+ADT。转移概率和效用来自文献。使用 10 年时间范围和 100,000 美元/质量调整生命年(QALY)的意愿支付阈值,随后为每种治疗策略计算了净货币收益值。
在 10 年时,基础病例显示总成本分别为 141,148 美元、166,807 美元和 136,154 美元,QALYs 分别为 4.63、4.89 和 4.00,反映出初始 MDT、初始 AAP+ADT 和初始多西他赛+ADT 的净货币收益分别为 322,240 美元、322,018 美元和 263,407 美元。使用蒙特卡罗模拟(1,000,000 次模拟)进行概率敏感性分析时,初始 MDT 在 53.6%的模拟中是具有成本效益的策略。概率敏感性分析显示,初始 MDT 的成本在 95%置信区间内(75,914-179,862 美元、124,431-223,892 美元和 103,298-180,617 美元),效用在 QALYs 中为 3.85-6.12(3.91-5.86,3.02-5.22)。
在 10 年时,初始 MDT 后行挽救性 AAP+ADT 与初始标准治疗系统治疗相比具有可比性的成本效益,可能是一种可行的治疗策略,特别是在那些出于生活质量或合并症考虑而希望推迟系统治疗的患者中。需要进一步的研究来确定 MDT 是否会导致疾病自然史的持续有意义的延迟,以及 MDT 是否与初始高级系统治疗相结合存在任何益处。