Understanding the Guideline-Discordant Use of Bone Modifying Agents in Prostate Cancer

项目摘要 骨修饰剂（BMA）可以改善转移性前列腺癌的生活质量。BMA唑来膦酸 酸和狄诺塞单抗预防转移性去势抵抗性前列腺癌男性骨折 （mCRPC），导致疼痛减轻和功能改善。但是，BMA可能会导致严重的副作用。 因为BMA不能预防转移性去势敏感性前列腺癌患者的骨折 （mCSPC），风险/获益平衡不支持这些患者使用BMA。由于这些原因， 国家综合癌症网络指南建议在mCRPC中使用BMA， 在mCSPC中的应用因此，患者结局可能受到BMA使用不足的不利影响， mCRPC患者和mCSPC患者中过度使用。然而，人们对真实的- BMA在前列腺癌中的全球应用。确定BMA使用不足和/或过度使用是否严重 为了解决这些问题，必须首先了解BMAs在前列腺癌中的应用模式。BMA药物也有 价值收益相对于财务成本的重要区别。唑来膦酸具有成本效益，但 而狄诺塞单抗的价格则要昂贵得多。使用地舒单抗代替唑来膦酸可能 因此，给病人和卫生系统造成了本可避免的费用。为了弥补这些知识差距，我们 建议使用SEER-Medicare数据描述BMA在前列腺癌中的真实使用。我们将确定两个 关键患者组：建议使用BMA的mCRPC患者和mCSPC患者， 其中BMA的使用是不鼓励的，将构成过度使用。我们将确定 每组内的BMA治疗，并描述与使用不足相关的患者和提供者因素 和过度使用我们还将评估地舒单抗使用的增加是否导致了额外的财务成本， 患者或医疗机构。目的1：测量骨修饰剂使用不足和过度使用的患病率 前列腺癌的治疗方法为了衡量潜在的使用不足，我们将使用SEER-Medicare数据来识别 mCRPC患者，并确定其是否接受BMA（目的1A）。为了衡量过度使用（目标1B），我们将 识别新诊断为mCSPC的患者，并确定是否接受了BMA。目标2：识别和描述 与骨修饰剂使用不足和过度使用相关的患者和提供者因素。我们将 使用SEER-Medicare数据识别关键的患者社会经济因素和提供者组织因素 与BMA使用不足（Aim 2A）和过度使用（Aim 2B）相关。目标3：评价利用 Denosumab和相关费用。我们将评估地舒单抗与 唑来膦酸（目标3A），并估计对患者和医疗保险（目标3B）产生的成本。影响：这个 这项研究将增加我们对前列腺癌中BMA利用的理解。研究结果可能会导致未来 通过减少BMA使用不足和过度使用来改善前列腺癌预后的干预性工作。

PROJECT SUMMARY Bone-modifying agents (BMAs) can improve quality-of-life in metastatic prostate cancer. The BMAs zoledronic acid and denosumab prevent bone fractures among men with metastatic, castration-resistant prostate cancer (mCRPC), resulting in reduced pain and improved function. However, BMAs can cause serious side effects. Because BMAs do not prevent fractures among men with metastatic, castration-sensitive prostate cancer (mCSPC), the risk/benefit balance does not support BMA use for these patients. For these reasons, the National Comprehensive Cancer Network Guidelines recommend for the use of BMAs in mCRPC, and against their use in mCSPC. Patient outcomes may therefore be adversely affected by both BMA underuse among patients with mCRPC and by overuse among patients with mCSPC. However, little is known about the real- world use of BMAs in prostate cancer. To determine whether BMA underuse and/or overuse are significant problems, the utilization patterns of BMAs for prostate cancer must first be understood. BMA drugs also have important differences in value – benefits relative to financial cost. Zoledronic acid is cost-effective, but denosumab, which is much more expensive, is not. The use of denosumab instead of zoledronic acid may therefore result in avoidable costs to patients and the health system. To address these knowledge gaps, we propose to describe real-world use of BMAs in prostate cancer using SEER-Medicare data. We will identify two key patient groups: those with mCRPC, among whom BMA use is recommended, and those with mCSPC, among whom BMA use is discouraged and would constitute overuse. We will determine the prevalence of BMA therapy within each group and characterize the patient and provider factors associated with underuse and overuse. We will also assess whether increased denosumab use has resulted in excess financial costs to patients or to Medicare. Aim 1: Measure the prevalence of underuse and overuse of bone-modifying agents in prostate cancer. To measure potential underuse, we will use SEER-Medicare data to identify patients with mCRPC and determine their receipt of BMAs (Aim 1A). To measure overuse (Aim 1B), we will identify patients newly diagnosed with mCSPC and determine receipt of BMAs. Aim 2: Identify and describe patient and provider factors associated with underuse and overuse of bone-modifying agents. We will use SEER-Medicare data to identify key patient socioeconomic factors and provider organizational factors associated with BMA underuse (Aim 2A) and overuse (Aim 2B). Aim 3: Evaluate changes in utilization of denosumab and associated costs. We will assess temporal trends in the relative use of denosumab vs. zoledronic acid (Aim 3A) and estimate resulting costs to patients and to Medicare (Aim 3B). Impact: This study will increase our understanding of BMA utilization in prostate cancer. Study results may lead to future interventional work to improve prostate cancer outcomes by reducing BMA underuse and overuse.