Outcomes of Prostate Cancer Androgen Deprivation Therapy

前列腺癌雄激素剥夺疗法的结果

• 批准号: 8055410
• 负责人: Arnold L Potosky
• 金额: $ 57.46万
• 依托单位: GEORGETOWN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-04-02 至 2013-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8055410
• 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' s group; mortality; neoplasm registry; novel; older men; palliative; post-market; prognostic; public health relevance; randomized trial; treatment effect; tumor; tumor progression; tumor registry

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）：在过去十年中，ADT作为未接受其他治愈性治疗（手术或放疗）的新诊断局限性疾病老年男性的主要治疗以及这些治愈性治疗失败后PSA升高的治疗越来越受欢迎。在这两组中，临床试验没有证明死亡率的好处，也不太可能进行试验。鉴于老年男性数量的增加，前列腺癌的高发病率和生存率，以及每年估计有100，000名前列腺癌男性使用ADT，迫切需要有关结果的信息，以告知治疗决策。我们建议评估最初诊断为局限性前列腺癌的男性接受雄激素剥夺治疗（ADT）后长达15年的致命性和病态结局。 除了缺乏死亡率获益的证据外，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）事件相关。我们的三个具体目标包括估计ADT在全因和前列腺癌特定死亡率方面的获益和风险，估计严重非致命性不良事件的发生率;以及评估常用处方药是否可以减轻ADT相关的危害。我们将根据年龄、分期、血清生物标志物值（PSA）和肿瘤侵袭性的其他病理标志物定义的预后风险组评估癌症特异性结局。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倚。 回顾性观察性研究将使用1995-2007年诊断的超过45，000名男性的大型多样化人群进行，平均随访6年。有来自3个大型综合医疗保健计划的该人群的全面计算机化临床利用数据，包括关于肿瘤特征、风险因素和结局的纵向信息。关键变量将来自住院、门诊、药房和放射学数据以及实验室检查值。与之前的观察性研究相比，我们将在整个疾病轨迹上结合规模，随访和详细的临床信息，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使用大型数据库进行前列腺癌结局研究方面经验丰富的多学科团队将产生改善治疗决策和结局所需的新的重要信息。 公共卫生相关性：激素治疗前列腺癌在过去十年中越来越受欢迎。然而，没有证据表明这种疗法可以延长疾病的生存期，并且其使用有几个潜在的严重的长期意外后果。这些不良反应包括骨折、心血管疾病和糖尿病。随机对照试验不计划评估这些问题。鉴于人口老龄化，以及估计每年有10万新男性使用激素疗法，迫切需要更好地了解结果，以便为治疗决定提供信息。在我们提出的研究中，我们将量化前列腺癌激素治疗的死亡率益处和不良反应。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1995-2007年在三个大型健康计划中诊断的45，000名男性的广泛信息。我们的研究结果将提供新的信息，帮助男性在开始激素治疗时做出更明智的决定。