Refining castration use for recurrent prostate cancer

项目摘要 项目背景：几乎所有被诊断患有前列腺癌的美国男性都已本地化 疾病。大多数人都接受了治疗，但大约三分之一的人通过前列腺癌复发 PSA水平。PSA升高的一种常见治疗方法是用长效注射药物去势 称为雄激素剥夺疗法(ADT)。了解这些患者ADT的最佳时机 男性很重要，因为大多数人没有复发癌症的症状，但会处理 生存希望的主要副作用(如糖尿病、骨质疏松症、肥胖、心脏病) 福利。然而，只有有限的证据来指导阉割的时机和使用 治疗后PSA水平升高。这导致了模糊的准则建议和 广泛的实践差异。一些男人是否可以避免阉割，它的副作用，或者 在不影响生存的情况下抵抗阉割仍不清楚。使用生物统计学 受现实世界实践变化影响的模型可以提炼出这些重要问题的答案。 项目目标：这项研究将结合基于人群的癌症登记和电子化 使用生物统计建模和随机试验记录来自国家交付系统的数据 用ADT检查去势对局部切除后进展和生存的影响的数据 前列腺癌的治疗。我们将利用可变的去势做法来确定 可能受益于或可能不受益于前列腺癌复发的去势的男性群体。 项目方法：这项与临床相关的高影响研究有三个目标。目标1：实现 检查局部前列腺癌治疗后去势使用的变化。我们将确定 2005-2015年间，使用国家癌症登记数据治疗局限性前列腺癌的男性。 我们将描述纵向去势实践的时间、连续性和 临床因素(如PSA、风险组、抢救放射治疗)使用国家行政管理 声明、药房和实验室，以及随机试验数据。目标2：评估 去势时机对前列腺癌进展的影响。我们将确定前列腺癌 我们基于人群的随机试验中抗去势疾病的进展 数据。我们将使用生物统计建模来确定与 最长的去势抵抗时间和生存结果。目标3：优化人口数量 男性最有可能从前列腺癌复发的去势中受益，以及何时。基于 我们的模型和补充数据集，我们将提出去势的标准和时间 帮助局部前列腺癌治疗后最大限度提高疗效的做法。对一些男人来说， 推迟或避免去势可能是最好的，对其他人来说，更早的去势可能是最好的。

Project Summary Project Background: Nearly all US men diagnosed with prostate cancer have localized disease. Most are treated, yet roughly one in three have their prostate cancer return via rising PSA levels. A common treatment for rising PSA is castration with long-acting injectable drugs termed androgen deprivation therapy (ADT). Understanding the best timing of ADT for these men is important because most do not have symptoms of recurrent cancer, yet will deal with major side effects (e.g., diabetes, osteoporosis, obesity, heart disease) in the hopes of survival benefits. However, there is limited evidence to guide castration timing and use when it comes to rising PSA levels after treatment. This results in vague guideline recommendations and widespread practice variation. Whether some men can avoid castration, its side effects, or castration-resistance without compromising survival remains unclear. Using biostatistical models informed by real-world practice variation can refine answers to these important issues. Project Objectives: This study will combine population-based cancer registry and electronic record data from a national delivery system with biostatistical modeling and randomized trial data to examine the impact of castration with ADT on progression and survival after localized prostate cancer treatment. We will take advantage of variable castration practices to identify populations of men that may and may not benefit from castration for recurrent prostate cancer. Project Methods: This clinically-relevant, high impact study has three aims. Aim 1: To examine variation in castration use after localized prostate cancer treatment. We will identify men treated for localized prostate cancer from 2005-2015 using national cancer registry data. We will characterize longitudinal castration practices with respect to timing, continuity, and clinical factors (e.g., PSA, risk group, salvage radiotherapy) using national administrative claims, pharmacy, and laboratory, as well as randomized trial data. Aim 2: To assess the impact of castration timing on prostate cancer progression. We will identify prostate cancer progression to castration-resistant disease among our population-based and randomized trial data. We will use biostatistical modeling to identify castration practices associated with the longest times to castration-resistance and survival outcomes. Aim 3: To refine populations of men most likely to benefit from castration for recurrent prostate cancer, and when. Based on our models and complementary datasets, we will propose criteria and timing for castration practices to help maximize outcomes after localized prostate cancer treatment. For some men, delaying or avoiding castration might be best, for others, earlier castration might be optimal.