Dorff Tanya B, Agarwal Neeraj
USC Keck School of Medicine, USC Norris Comprehensive Cancer Center, Genitourinary Oncology, Los Angeles, CA 90033, USA.
Hunts Man Cancer Institute, University of Utah, 2000 Circle of Hope, Salt Lake City, UT 84112, USA.
Asian J Androl. 2018 May-Jun;20(3):215-220. doi: 10.4103/aja.aja_12_18.
Bone metastases are the main driver of morbidity and mortality in advanced prostate cancer. Targeting the bone microenvironment, a key player in the pathogenesis of bone metastasis, has become one of the mainstays of therapy in men with advanced prostate cancer. This review will evaluate the data supporting the use of bone-targeted therapy, including (1) bisphosphonates such as zoledronic acid, which directly target osteoclasts, (2) denosumab, a receptor activator of nuclear factor-kappa B (RANK) ligand inhibitor, which targets a key component of bone stromal interaction, and (3) radium-223, an alpha-emitting calcium mimetic, which hones to the metabolically active areas of osteoblastic metastasis and induces double-strand breaks in the DNA. Denosumab has shown enhanced delay in skeletal-related events compared to zoledronic acid in patients with metastatic castration-resistant prostate cancer (mCRPC). Data are mixed with regard to pain control as a primary measure of efficacy. New data call into question dosing frequency, with quarterly dosing strategy potentially achieving similar effect compared to monthly dosing for zoledronic acid. In the case of radium-223, there are data for both pain palliation and improved overall survival in mCRPC. Further studies are needed to optimize timing and combination strategies for bone-targeted therapies. Ongoing studies will explore the impact of combining bone-targeted therapy with investigational therapeutic agents such as immunotherapy, for advanced prostate cancer. Future studies should strive to develop biomarkers of response, in order to improve efficacy and cost-effectiveness of these agents.
骨转移是晚期前列腺癌发病和死亡的主要驱动因素。针对骨微环境（骨转移发病机制中的关键因素）已成为晚期前列腺癌男性患者治疗的主要手段之一。本综述将评估支持使用骨靶向治疗的数据，包括：（1）双膦酸盐类药物，如唑来膦酸，其直接作用于破骨细胞；（2）地诺单抗，一种核因子κB受体激活剂配体抑制剂，作用于骨基质相互作用的关键成分；（3）镭-223，一种发射α粒子的钙模拟物，可聚集在成骨性转移的代谢活跃区域并诱导DNA双链断裂。在转移性去势抵抗性前列腺癌（mCRPC）患者中，与唑来膦酸相比，地诺单抗已显示出在延迟骨相关事件方面效果更佳。关于作为主要疗效指标的疼痛控制，数据存在差异。新数据对给药频率提出质疑，唑来膦酸每季度给药策略可能与每月给药效果相似。就镭-223而言，有数据表明其对mCRPC患者有减轻疼痛和改善总生存期的作用。需要进一步研究以优化骨靶向治疗的时机和联合策略。正在进行的研究将探索骨靶向治疗与免疫治疗等研究性治疗药物联合用于晚期前列腺癌的影响。未来的研究应努力开发反应生物标志物，以提高这些药物的疗效和成本效益。
