Boopathi Ettickan, Birbe Ruth, Shoyele Sunday A, Den Robert B, Thangavel Chellappagounder
Center for Translational Medicine, Department of Medicine, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Laboratory Medicine, Department of Pathology, Cooper University Health Care, Camden, NJ 08103, USA.
Cancers (Basel). 2022 Sep 2;14(17):4305. doi: 10.3390/cancers14174305.
Prostate cancer (PCa) is the second-leading cause of cancer-related deaths in men. PCa cells require androgen receptor (AR) signaling for their growth and survival. Androgen deprivation therapy (ADT) is the preferred treatment for patients with locally advanced and metastatic PCa disease. Despite their initial response to androgen blockade, most patients eventually will develop metastatic castration-resistant prostate cancer (mCRPC). Bone metastases are common in men with mCRPC, occurring in 30% of patients within 2 years of castration resistance and in >90% of patients over the course of the disease. Patients with mCRPC-induced bone metastasis develop lesions throughout their skeleton; the 5-year survival rate for these patients is 47%. Bone-metastasis-induced early changes in the bone that proceed the osteoblastic response in the bone matrix are monitored and detected via modern magnetic resonance and PET/CT imaging technologies. Various treatment options, such as targeting osteolytic metastasis with bisphosphonates, prednisone, dexamethasone, denosumab, immunotherapy, external beam radiation therapy, radiopharmaceuticals, surgery, and pain medications are employed to treat prostate-cancer-induced bone metastasis and manage bone health. However, these diagnostics and treatment options are not very accurate nor efficient enough to treat bone metastases and manage bone health. In this review, we present the pathogenesis of PCa-induced bone metastasis, its deleterious impacts on vital organs, the impact of metastatic PCa on bone health, treatment interventions for bone metastasis and management of bone- and skeletal-related events, and possible current and future therapeutic options for bone management in the continuum of prostate cancer disease.
前列腺癌(PCa)是男性癌症相关死亡的第二大原因。PCa细胞的生长和存活需要雄激素受体(AR)信号传导。雄激素剥夺疗法(ADT)是局部晚期和转移性PCa疾病患者的首选治疗方法。尽管大多数患者最初对雄激素阻断有反应,但最终大多数患者会发展为转移性去势抵抗性前列腺癌(mCRPC)。骨转移在mCRPC男性中很常见,30%的患者在去势抵抗2年内发生骨转移,超过90%的患者在疾病过程中会发生骨转移。mCRPC引起的骨转移患者全身骨骼都会出现病变;这些患者的5年生存率为47%。通过现代磁共振和PET/CT成像技术监测和检测骨转移引起的骨早期变化,这些变化先于骨基质中的成骨细胞反应。目前采用了各种治疗方案,如用双膦酸盐、泼尼松、地塞米松、地诺单抗、免疫疗法、外照射放疗、放射性药物、手术和止痛药靶向溶骨性转移,以治疗前列腺癌引起的骨转移并管理骨骼健康。然而,这些诊断和治疗方案在治疗骨转移和管理骨骼健康方面不够准确和有效。在这篇综述中,我们阐述了PCa诱导骨转移的发病机制、其对重要器官的有害影响、转移性PCa对骨骼健康的影响、骨转移的治疗干预措施以及骨和骨骼相关事件的管理,以及前列腺癌疾病连续过程中当前和未来可能的骨骼管理治疗选择。