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

项目总结 骨改良剂(BMA)可以改善转移性前列腺癌患者的生活质量。BMA的唑来膦酸 酸和地诺单抗预防男性转移性去势耐受前列腺癌患者的骨折 (MCRPC)，从而减轻疼痛和改善功能。然而，BMA可能会引起严重的副作用。 因为BMA不能预防男性转移性、去势敏感型前列腺癌患者的骨折 (MCSPC)，风险/收益平衡不支持这些患者使用BMA。出于这些原因， 国家综合癌症网络指南建议在mCRPC中使用BMA，并反对 它们在mCSPC中的应用。因此，患者的预后可能会受到以下两种情况的不利影响 MCRPC患者和mCSPC患者中过度使用。然而，人们对真实的- BMA在全球前列腺癌治疗中的应用。确定BMA使用不足和/或过度是否严重 问题，首先必须了解BMA在前列腺癌中的利用模式。BMA药物也有 价值收益相对于财务成本的重要差异。唑来膦酸具有成本效益，但 价格高得多的Denosumab并非如此。使用地诺舒单抗替代唑来膦酸可 因此，给患者和卫生系统带来了可避免的成本。为了解决这些知识差距，我们 建议使用SEER-Medicare数据描述BMA在前列腺癌中的真实应用。我们将确定两个 重点患者群体：mCRPC患者，其中推荐使用BMA；mCSPC患者， 其中，不鼓励使用BMA，并将构成过度使用。我们将确定该病的流行率 每组中的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。我们还将评估非那单抗使用量的增加是否导致了额外的财务成本 病人或联邦医疗保险。目标1：测量骨修饰使用不足和过度使用的流行率 前列腺癌的药物。为了衡量潜在的使用不足，我们将使用SEER-Medicare数据来确定 MCRPC患者并确定他们接受BMA的情况(目标1A)。为了衡量过度使用(目标1B)，我们将 确定新诊断的mCSPC患者，并确定BMA的收受情况。目标2：确定和描述 与骨改良剂使用不足和过度使用相关的患者和提供者因素。我们会 使用SEER-Medicare数据确定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(目标2A)和过度使用(目标2B)有关。目标3：评价利用情况的变化 Denosumab及相关费用。我们将评估相对使用denosumab与 唑来膦酸(目标3A)，并估计由此给患者和医疗保险带来的成本(目标3B)。影响：这 这项研究将增加我们对BMA在前列腺癌中应用的理解。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.