Outcomes of Prostate Cancer Androgen Deprivation Therapy

描述（由申请人提供）：在过去的十年中，ADT作为未接受其他治疗目的治疗（手术或放疗）的新诊断的局限性疾病的老年男性的主要治疗方法越来越受欢迎，并作为治疗这些治疗失败后PSA上升的治疗方法。在这两组中，没有证据表明临床试验对死亡率有好处，也不太可能进行试验。鉴于老年男性人数的增加，前列腺癌的高发病率和生存率，以及每年约有10万前列腺癌患者使用ADT，迫切需要有关结果的信息，以便为治疗决策提供信息。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）后长达15年的死亡和发病结果。除了缺乏降低死亡率的证据外，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：从全因死亡率和前列腺癌特异性死亡率的角度估计ADT的获益和风险，估计严重非致命性不良事件的发生率；并评估常用的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、血清生物标志物值（PSA）和其他肿瘤侵袭性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。这项回顾性观察性研究将对1995年至2007年间确诊的45000多名男性进行研究，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综合计算机临床利用数据，包括肿瘤特征、危险因素和结果的纵向信息。关键变量将从住院、门诊、药房和放射学数据和实验室测试值中得出。与之前的观察性研究相比，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，以显着提高与ADT相关的风险估计的准确性。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局研究方面的经验，将为改善治疗决策和结果提供新的重要信息。

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.