Outcomes of Prostate Cancer Androgen Deprivation Therapy

描述(申请人提供)：ADT在过去十年中越来越受欢迎，作为新诊断的局部疾病未接受其他治疗意图治疗(手术或放射治疗)的老年男性的主要治疗方法，以及作为这些治疗失败后PSA上升的治疗方法。在这两组人中，都没有从临床试验中证实对死亡率有好处，而且不太可能进行试验。鉴于老年男性的数量不断增加，前列腺癌的高发病率和存活率，以及每年估计有10万名前列腺癌男性患者使用ADT，迫切需要有关结果的信息，以指导治疗决定。我们建议评估最初诊断为局限性前列腺癌的男性在雄激素剥夺治疗(ADT)后15年内的死亡和病态结果。除了缺乏对死亡率有益的证据外，越来越多的证据表明，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。我们的三个具体目标包括根据所有原因和前列腺癌特定死亡率来评估ADT的益处和风险，估计严重非致命性不良事件的比率，以及评估常用处方药是否可以减轻与ADT相关的危害。我们将根据年龄、分期、血清生物标记物价值(PSA)和其他肿瘤侵袭性的病理标记物定义的预后风险组来评估特定于癌症的预后。对于不良事件估计，我们将考虑基线合并症和临床预测因素的变化，并将使用最先进的有效性分析技术来纠正选择偏差。这项回溯性观察性研究将使用1995-2007年间确诊的45000多名男性中的大量不同人群进行，平均随访时间为6年。有来自3个大型综合医疗保健计划的全面的计算机化的该人群的临床利用数据，包括关于肿瘤特征、风险因素和结果的纵向信息。关键变量将来自住院患者、门诊患者、药房和放射学数据以及实验室测试值。与以前的观察性研究不同，我们的研究将结合规模、随访和整个疾病轨迹的详细临床信息，以显著提高与ADT相关的风险估计的精确度。这些优势，以及我们的多学科团队在使用大型数据库进行前列腺癌结果研究方面的经验，将产生改善治疗决策和结果所需的新的重要信息。 与公共卫生相关：前列腺癌的激素疗法在过去十年里变得越来越受欢迎。然而，没有证据表明这种疗法可以延长疾病的存活期，而且使用它有几个潜在的严重的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。不计划进行随机对照试验来评估这些问题。鉴于人口老龄化，以及估计每年有100,000名新男性使用激素疗法，迫切需要更好的结果信息，以指导治疗决定。在我们提议的研究中，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年间在三个大型健康计划中确诊的45,000名男性的广泛信息。我们的结果将提供新的信息，帮助男性做出关于开始激素治疗的更明智的决定。

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.