Outcomes of Prostate Cancer Androgen Deprivation Therapy

前列腺癌雄激素剥夺疗法的结果

基本信息

批准号：
8247007
负责人：
Arnold L Potosky
金额：
$ 54.91万
依托单位：
GEORGETOWN UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-04-02 至 2014-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8247007
关键词：
Accounting Address Adjuvant Adverse effects Adverse event Aftercare Age Algorithms Americas Androgens Benefits and Risks Biochemical Biological Markers California Cancer Research Network Cancer Survivor Cardiac Cardiovascular Diseases Cardiovascular system Cause of Death Cessation of life Characteristics Clinical Clinical Trials Comorbidity Coronary Coronary heart disease Data Data Linkages Databases Decision Making Diabetes Mellitus Diagnosis Disease Disease Outcome Disease Progression Effectiveness Elderly man Endocrine Ensure Equilibrium Event Face Failure Fatal Outcome Fracture Future Gleason Grade for Prostate Cancer Gray unit of radiation dose Health Planning Health system Healthcare Hyperlipidemia Incidence Information Technology Inpatients Institute of Medicine (U.S.)Investments Knowledge Laboratories Link Lipids Localized Disease Longitudinal Studies Malignant Neoplasms Malignant neoplasm of prostate Measures Medicare Morbidity - disease rate Musculoskeletal National Cancer Institute Newly Diagnosed Observational Study Operative Surgical Procedures Outcome Outcomes Research Outpatients Palliative Care Patient Selection Patient observation Patients Persons Pharmaceutical Preparations Pharmacy facility Population Population Heterogeneity Preventive Probability Prostate Prostate-Specific Antigen Public Health Radiation Radiation therapy Radiology Specialty Randomized Controlled Trials Recurrence Reporting Research Resources Risk Risk Estimate Risk Factors Selection Bias Selection for Treatments Serious Adverse Event Serum Staging Survival Rate Survivors Techniques Testing Therapeutic Tumor Markers Uncertainty United States Variant advanced disease adverse outcome age group bisphosphonate bone loss cancer diagnosis cancer therapy cardiovascular risk factor clinical practice cohort computerized cost deprivation diabetic experience follow-up high risk hormone therapy improved innovation men men&apos s group mortality neoplasm registry novel older men palliative post-market prognostic public health relevance randomized trial treatment effect tumor tumor progression tumor registry

项目摘要

DESCRIPTION (provided by applicant): ADT has become increasingly popular over the past decade as primary therapy for older men with newly diagnosed localized disease not receiving other curative intent treatments (surgery or radiotherapy), and as a treatment for a rising PSA after failure of these curative therapies. In both groups, there is no proven mortality benefit from clinical trials, and it is unlikely that trials will be conducted. Given the increasing number of elderly men, the high incidence and survival rates from prostate cancer, and the use of ADT in an estimated 100,000 men with prostate cancer each year, there is urgent need for information on outcomes to inform treatment decisions. We propose to assess fatal and morbid outcomes up to 15 years following androgen deprivation therapy (ADT) for men initially diagnosed with localized prostate cancer. In addition to lack of evidence of a mortality benefit, there is emerging evidence suggesting that ADT may be associated with increased cardiovascular mortality, as well as musculoskeletal (bone fractures), cardiovascular, and endocrine-related (diabetic) events. Our three specific aims include estimating the benefits and risks of ADT in terms of all cause and prostate-cancer specific mortality, estimating the rate of serious non-fatal adverse events; and assessing whether commonly used prescription medications can lessen the harms associated with ADT. We will assess cancer-specific outcomes according to prognostic risk groups defined by age, stage, serum biomarker values (PSA), and other pathological markers of tumor aggressiveness. For adverse event estimates, we will account for variations in baseline comorbidity and clinical predictors, and will use state-of-the-art effectiveness analysis techniques to correct for selection bias. The retrospective observational study will be conducted using a large, diverse population of over 45,000 men diagnosed from 1995-2007 with a mean follow up of 6 years. There are comprehensive computerized clinical utilization data for this population from 3 large integrated health care plans, including longitudinal information on tumor characteristics, risk factors and outcomes. Key variables will be derived from inpatient, outpatient, pharmacy and radiology data and lab test values. In contrast to prior observational studies, ours will have the combination of size, follow up, and detailed clinical information over the entire disease trajectory needed to significantly improve the precision of risk estimates associated with ADT. These strengths, and our multi-disciplinary team experienced in prostate cancer outcomes research using large databases, will yield new and important information needed to improve treatment decision making and outcomes. PUBLIC HEALTH RELEVANCE: Hormonal therapy for prostate cancer has become increasingly popular over the past decade. However, there is no proof that this therapy can prolong survival from the disease, and there are several potentially serious long-term unintended consequences from its use. These adverse effects include bone fractures, cardiovascular disease, and diabetes. Randomized controlled trials are not planned to evaluate these issues. Given the ageing of the population, and the use of hormonal therapy in an estimated 100,000 new men each year, there is an urgent need for better information on outcomes to inform treatment decisions. In our proposed study we will quantify the mortality benefits and adverse effects of hormonal therapy for prostate cancer. To perform this study we will use a detailed clinical database containing extensive information on 45,000 men diagnosed in 1995-2007 in three large health plans. Our results will provide new information to help men make more informed decisions about starting hormonal therapy.

描述（由申请人提供）：在过去的十年中，ADT是针对新诊断的局部疾病未接受其他治疗性治疗（手术或放射疗法）的老年男性的主要疗法，并且是这些治疗疗法失败后PSA的治疗方法。在这两组中，临床试验均无证实的死亡率，并且不太可能进行试验。鉴于老年男性的数量增加，前列腺癌的发病率和存活率高，并且每年估计有100,000名前列腺癌男性使用ADT，因此迫切需要有关结果的信息来告知治疗决策。我们建议评估最初诊断为局部前列腺癌的男性雄激素剥夺疗法（ADT）后长达15年的致命结局。除了缺乏死亡率益处的证据外，还有新的证据表明ADT可能与心血管死亡率增加以及肌肉骨骼（骨折），心血管和内分泌相关（糖尿病）事件有关。我们的三个具体目的包括根据所有原因和前列腺癌的死亡率估算ADT的收益和风险，从而估计严重的非致命不良事件的率；并评估常用处方药是否可以减轻与ADT相关的危害。我们将根据由年龄，阶段，血清生物标志物值（PSA）和其他肿瘤攻击性的其他病理标记定义的预后风险群体评估癌症特异性结果。对于不良事件估计，我们将考虑基线合并症和临床预测因子的变化，并将使用最先进的有效性分析技术来纠正选择偏差。回顾性观察研究将使用1995年至2007年诊断出的45,000多名男子的大量人群进行，平均随访为6年。来自3个大型综合医疗保健计划，包括有关肿瘤特征，危险因素和结果的纵向信息，为该人群提供了全面的计算机临床利用数据。关键变量将来自住院，门诊，药学和放射学数据以及实验室测试值。与先前的观察性研究相反，我们的大小，跟进和详细的临床信息的结合在整个疾病轨迹上，以显着提高与ADT相关的风险估计的精度。这些优势以及我们在前列腺癌结果研究中经历了大型数据库中经验丰富的多学科团队，将产生改善治疗决策和结果所需的新的重要信息。公共卫生相关性：在过去十年中，前列腺癌的荷尔蒙治疗变得越来越流行。但是，没有证据表明这种疗法可以延长疾病的生存，并且由于其使用而产生了几种潜在的严重长期意想不到的后果。这些不良反应包括骨折，心血管疾病和糖尿病。没有计划评估这些问题的随机对照试验。鉴于人口的老龄化以及每年估计有100,000名新男性的荷尔蒙疗法的使用，因此迫切需要更好地了解结果以告知治疗决策。在我们提出的研究中，我们将量化荷尔蒙治疗对前列腺癌的死亡率益处和不利影响。为了进行这项研究，我们将使用一个详细的临床数据库，其中包含有关1995 - 2007年诊断出的45,000名男性在三个大型健康计划中诊断出的大量信息。我们的结果将提供新的信息，以帮助男性做出有关开始荷尔蒙治疗的更明智的决定。

项目成果

期刊论文数量（3）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Cardiovascular disease risk and androgen deprivation therapy in patients with localised prostate cancer: a prospective cohort study.

DOI：
10.1038/bjc.2017.280
发表时间：
2017-10-10
期刊：
British journal of cancer
影响因子：
8.8
作者：
Haque R;UlcickasYood M;Xu X;Cassidy-Bushrow AE;Tsai HT;Keating NL;Van Den Eeden SK;Potosky AL
通讯作者：
Potosky AL

Androgen deprivation therapy for treatment of localized prostate cancer and risk of second primary malignancies.