Refining castration use for recurrent prostate cancer

改善复发性前列腺癌的去势疗法

• 批准号: 10395960
• 负责人: Ted Albert Skolarus
• 金额: $ 33.57万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-05-01 至 2024-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10395960
• 关键词: Aftercare; Biometry; Castration; Chemicals; Clinical; Coupling; Data; Data Set; Diabetes Mellitus; Diagnosis; Disease Resistance; Drug resistance; Guidelines; Heart Diseases; Injectable; Laboratories; Localized Disease; Malignant neoplasm of prostate; Methods; Modeling; Neoplasm Metastasis; Obesity; Osteoporosis; Outcome; PSA level; Pain; Patients; Pattern; Pharmaceutical Preparations; Pharmacy facility; Population; Prostate Cancer therapy; Provider; Radiation therapy; Recommendation; Recurrence; Recurrent Malignant Neoplasm; Resistance; Risk; Symptoms; System; Testosterone; Time; Treatment Failure; Variant; androgen deprivation therapy; base; cancer survival; clinical decision-making; clinically relevant; common treatment; comorbidity; data registry; male; men; men' s group; neoplasm registry; population based; prostate cancer progression; randomized trial; side effect; survival outcome; tumor progression

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.

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有局部 疾病大多数人都接受了治疗，但大约三分之一的人的前列腺癌通过升高而复发。 PSA水平。PSA升高的常见治疗方法是使用长效注射药物进行去势 称为雄激素剥夺疗法（ADT）。了解ADT的最佳时机， 男性是重要的，因为大多数人没有复发性癌症的症状，但将处理 主要副作用（例如，糖尿病、骨质疏松症、肥胖症、心脏病）， 效益然而，有有限的证据来指导阉割时机和使用时， 治疗后PSA水平升高。这导致了模糊的指南建议， 广泛的实践差异。是否有些男人可以避免阉割，它的副作用，或 不影响生存的去势抵抗仍不清楚。使用生物统计学 根据实际做法的变化建立的模型可以完善这些重要问题的答案。 项目目的：本研究将结合联合收割机人群为基础的癌症登记和电子 通过生物统计学建模和随机试验记录来自国家输送系统的数据 检查ADT去势对局部治疗后进展和生存率的影响的数据 前列腺癌的治疗我们将利用各种阉割实践来识别 男性群体可能会和可能不会受益于去势复发性前列腺癌。 项目方法：这项临床相关的高影响力研究有三个目标。目标1： 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。 我们将描述纵向阉割实践的时间，连续性， 临床因素（例如，PSA、风险组、挽救性放疗），使用国家行政 索赔，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。我们将鉴别前列腺癌 在我们的基于人群的随机试验中进展为去势抵抗性疾病 数据我们将使用生物统计建模来识别与 最长的去势抵抗时间和生存结果。目标3：完善 男性最有可能受益于去势复发性前列腺癌，以及何时。基于 我们的模型和补充数据集，我们将提出阉割的标准和时间 实践，以帮助最大限度地提高局部前列腺癌治疗后的结果。对某些男人来说， 延迟或避免阉割可能是最好的，对于其他人来说，早期阉割可能是最佳的。