Contemporary role of androgen deprivation therapy for prostate cancer.
Contemporary role of androgen deprivation therapy for prostate cancer.
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DOI：
10.1016/j.eururo.2011.08.026
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发表时间：
2012-01
期刊：
影响因子：
23.4
通讯作者：
Studer, Urs E.
中科院分区：
文献类型：
--
作者：
Pagliarulo, Vincenzo;Bracarda, Sergio;Eisenberger, Mario A.;Mottet, Nicolas;Schroeder, Fritz H.;Sternberg, Cora N.;Studer, Urs E.
前列腺癌（PCa）的雄激素剥夺治疗（ADT）是已知的实体瘤最有效的全身姑息治疗之一。尽管临床试验已经评估了ADT在转移性和晚期局部疾病患者中的作用，但风险-获益比，特别是在早期阶段，仍然定义不清。鉴于越来越多的证据表明短期和长期ADT可能危及生命的不良反应，重新定义ADT在这种疾病中的作用非常重要。审查已发表的在各种当代PCa临床环境中使用现有ADT方法的经验以及报告的严重治疗相关不良事件。本综述讨论了与ADT治疗PCa相关的证据水平，重点关注生存结局指标。此外，本文还讨论了针对雄激素受体信号通路的不断发展的方法和新化合物临床试验的新证据。对文献进行了全面回顾，重点关注过去10年（2000年1月至2011年7月）的数据，并使用雄激素剥夺、激素治疗、前列腺癌和不良反应等术语。还对2010年和2011年举行的国际会议上报告的试验摘要进行了评价。随机对照试验和基于人群的研究的数据在不同的临床范式进行了分析。具体而言，在非转移性疾病患者中评价ADT作为主要和唯一治疗、与放疗（RT）联合或手术后以及转移性疾病患者中的作用。数据表明，在非转移性疾病男性患者中，使用ADT作为单药治疗未显示出获益，不推荐使用，而ADT联合常规剂量RT（<72戈伊）治疗高危疾病患者可能会延迟进展并延长生存期。在前瞻性研究中，ADT的术后使用仍然评价不佳。同样，没有试验评估ADT在手术或RT后生化复发患者中的作用。在转移性疾病患者中，ADT在生活质量、降低疾病相关发病率和可能的生存率方面具有明显的获益。双侧睾丸切除术、促黄体生成素释放激素激动剂治疗、联合或不联合抗雄激素治疗与各种严重不良事件相关，包括心血管疾病、糖尿病和骨骼并发症，这些并发症也可能影响死亡率。虽然ADT是PCa的有效治疗方法，但在晚期/转移性疾病患者中或ADT与RT（<72戈伊）联合用于高危肿瘤患者时，在生活质量和数量方面的长期获益主要明显。ADT的实施应以证据为基础，特别考虑不良事件和风险受益比。
Androgen deprivation therapy (ADT) for prostate cancer (PCa) represents one of the most effective systemic palliative treatments known for solid tumors. Although clinical trials have assessed the role of ADT in patients with metastatic and advanced locoregional disease, the risk–benefit ratio, especially in earlier stages, remains poorly defined. Given the mounting evidence for potentially life-threatening adverse effects with short- and long-term ADT, it is important to redefine the role of ADT for this disease. Review the published experience with currently available ADT approaches in various contemporary clinical settings of PCa and reported serious treatment-related adverse events. This review addresses the level of evidence associated with the use of ADT in PCa, focusing upon survival outcome measures. Furthermore, this paper discusses evolving approaches targeting androgen receptor signaling pathways and emerging evidence from clinical trials with newer compounds. A comprehensive review of the literature was performed, focusing on data from the last 10 yr (January 2000 to July 2011) and using the terms androgen deprivation, hormone treatment, prostate cancer and adverse effects. Abstracts from trials reported at international conferences held in 2010 and 2011 were also evaluated. Data from randomized controlled trials and population-based studies were analyzed in different clinical paradigms. Specifically, the role of ADT was evaluated in patients with nonmetastatic disease as the primary and sole treatment, in combination with radiation therapy (RT) or after surgery, and in patients with metastatic disease. The data suggest that in men with nonmetastatic disease, the use of primary ADT as monotherapy has not shown a benefit and is not recommended, while ADT combined with conventional-dose RT (<72 Gy) for patients with high-risk disease may delay progression and prolong survival. The postoperative use of ADT remains poorly evaluated in prospective studies. Likewise, there are no trials evaluating the role of ADT in patients with biochemical relapses after surgery or RT. In patients with metastatic disease, there is a clear benefit in terms of quality of life, reduction of disease-associated morbidity, and possibly survival. Treatment with bilateral orchiectomy, luteinizing hormone–releasing hormone agonist therapy, with and without antiandrogens has been associated with various serious adverse events, including cardiovascular disease, diabetes, and skeletal complications that may also affect mortality. Although ADT is an effective treatment of PCa, consistent long-term benefits in terms of quality and quantity of life are predominantly evident in patients with advanced/metastatic disease or when ADT is used in combination with RT (<72 Gy) in patients with high-risk tumors. Implementation of ADT should be evidence based, with special consideration to adverse events and the risk–benefit ratio.
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影响因子：
158.5
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