Massachusetts General Hospital, Medicine, Division of Hematology-Oncology, 55 Fruit Street, Yawkey 7E, Boston, MA 02114, USA.
Eur Urol. 2013 Feb;63(2):309-20. doi: 10.1016/j.eururo.2012.10.007. Epub 2012 Nov 23.
Bone metastases are a common feature of advanced genitourinary malignancies and a prominent cause of morbidity and mortality.
The objective of this review is to discuss the incidence, pathophysiology, and management of bone metastases in the most prevalent genitourinary malignancies.
We reviewed the relevant medical literature, with a particular emphasis on prospective randomized controlled trials. Much of the relevant clinical trial data focus on prostate cancer (PCa). We provide a nonsystematic review and our perspective on the available data.
Clinical manifestations can include pain, hypercalcemia, pathologic fractures, and spinal cord compression. Optimal systemic therapy for skeletal metastases often features a combination of disease-specific therapy and bone-targeted therapy. Some agents, such as the radiopharmaceutical radium-223, blur the line between those categories. Osteoclast inhibition is a validated strategy in the management of selected patients with bone metastases. Zoledronic acid, a bisphosphonate, is approved for the prevention of skeletal events caused by solid tumors metastatic to bone. Denosumab is a fully human monoclonal antibody that inactivates receptor activator of nuclear factor-κB ligand and is approved for the same indication. Beta-emitting radiopharmaceuticals can be effective for the palliation of pain caused by bone metastases, but their use is often limited by marrow suppression. The alpha-emitting radiopharmaceutical radium-223 has recently been shown to improve overall survival and prevent skeletal events in select men with castration-resistant PCa metastatic to bone. Multiple ongoing clinical trials are designed to examine the potential for therapeutic inhibition of additional targets such as Src and hepatocyte growth factor (MET).
Bone metastases cause considerable morbidity and mortality among patients with genitourinary malignancies. Optimal management requires consideration of bone-targeted therapy as well as disease-specific therapy. Further research is needed to optimize the use of existing agents and to define the therapeutic potential of novel targets.
骨转移是晚期泌尿生殖系统恶性肿瘤的常见特征，也是发病率和死亡率升高的主要原因。
本综述旨在讨论最常见的泌尿生殖系统恶性肿瘤中骨转移的发生率、病理生理学和治疗方法。
我们复习了相关的医学文献，特别强调了前瞻性随机对照试验。大量相关临床试验数据集中在前列腺癌（PCa）。我们提供了非系统性综述和对现有数据的看法。
临床表现可包括疼痛、高钙血症、病理性骨折和脊髓压迫。骨骼转移的最佳全身治疗通常包括疾病特异性治疗和骨靶向治疗的联合。一些药物，如放射性核素镭-223，模糊了这些类别之间的界限。破骨细胞抑制是治疗选定骨转移患者的一种已验证的策略。唑来膦酸是一种双膦酸盐，被批准用于预防转移性骨肿瘤引起的骨骼事件。地舒单抗是一种完全人源化单克隆抗体，可使核因子-κB 配体受体失活，也被批准用于相同的适应症。β发射放射性药物可有效缓解骨转移引起的疼痛，但由于骨髓抑制，其使用通常受到限制。α发射放射性药物镭-223最近已被证明可改善特定去势抵抗性前列腺癌转移性骨肿瘤患者的总生存期并预防骨骼事件。多项正在进行的临床试验旨在研究治疗性抑制其他靶点（如Src 和肝细胞生长因子（MET））的潜力。
骨转移给泌尿生殖系统恶性肿瘤患者带来了相当大的发病率和死亡率。最佳治疗需要考虑骨靶向治疗以及疾病特异性治疗。需要进一步研究以优化现有药物的使用并确定新靶标的治疗潜力。
