Montefiore Medical Center, 111 East 210th Street, New York, NY 10467, USA.
Centre Hospitalier de I'Université de Montréal, Hôpital Notre-Dame, 1560 Sherbrooke East, Montreal, QC H2L 4M1, Canada.
Nat Rev Clin Oncol. 2014 Jun;11(6):335-45. doi: 10.1038/nrclinonc.2014.70. Epub 2014 May 13.
Advanced-stage prostate cancer is associated with skeletal complications related to metastatic disease and its treatment. On the one hand, metastatic disease to bone is commonly associated with skeletal-related events (SREs); on the other hand, treatment with androgen-deprivation therapy (ADT) leads to loss in bone mineral density (BMD) and increased risk of fracture. Despite osteoblastic appearance on radiography, bone metastases from prostate cancer are associated with increased osteoblast and osteoclast activity providing the rationale for treatment with osteoclast-targeted agents. The bisphosphonate zoledronic acid and the monoclonal antibody denosumab reduce the incidence of SREs in metastatic castration-resistant prostate cancer (mCRPC). A number of agents prevent loss of BMD associated with ADT, but only denosumab is approved to reduce fractures in patients with non-metastatic prostate cancer. Another recently approved agent-radium-223-improves survival and delays SREs in mCRPC. The inhibitors of androgen receptor signalling, abiraterone and enzalutamide, improve survival in mCRPC and delay SREs, although the latter is likely related to control of disease rather than a direct effect on bone. Finally, the tyrosine kinase inhibitor cabozantinib shows promising activity in bone metastases from mCRPC. This Review addresses the skeletal morbidity associated with prostate cancer and the therapeutic options that exist to treat it.
晚期前列腺癌与转移性疾病及其治疗相关的骨骼并发症有关。一方面,转移性骨病常与骨骼相关事件(SREs)有关;另一方面,去势治疗(ADT)会导致骨密度(BMD)丧失和骨折风险增加。尽管前列腺癌的骨转移在影像学上表现为成骨样,但与增加的成骨细胞和破骨细胞活性相关,为使用破骨细胞靶向药物提供了治疗依据。双膦酸盐唑来膦酸和单克隆抗体地舒单抗可降低转移性去势抵抗性前列腺癌(mCRPC)中 SREs 的发生率。一些药物可预防 ADT 相关的 BMD 丢失,但只有地舒单抗被批准用于降低非转移性前列腺癌患者的骨折风险。另一种最近批准的镭-223可改善 mCRPC 的生存率并延迟 SREs。雄激素受体信号抑制剂阿比特龙和恩扎鲁胺可改善 mCRPC 的生存率并延迟 SREs,尽管后者可能与控制疾病有关,而不是直接作用于骨骼。最后,酪氨酸激酶抑制剂卡博替尼在 mCRPC 的骨转移中显示出有希望的活性。这篇综述探讨了与前列腺癌相关的骨骼发病率以及可用于治疗这些疾病的治疗选择。