Wenzel Mike, Hoeh Benedikt, Humke Clara, Welte Maria, Cano Garcia Cristina, Siech Carolin, Saad Fred, Karakiewcz Pierre I, Tilki Derya, Steuber Thomas, Graefen Markus, Traumann Miriam, Chun Felix K H, Mandel Philipp
Department of Urology, University Hospital Frankfurt, Goethe University Frankfurt am Main, Frankfurt, 63010, Germany.
Cancer Prognostics and Health Outcomes Unit, Division of Urology, University of Montréal Health Center, Montreal, Quebec, Canada.
JBMR Plus. 2024 Nov 26;9(1):ziae157. doi: 10.1093/jbmrpl/ziae157. eCollection 2025 Jan.
Hormonal agents administered for metastatic castration-resistant prostate cancer (mCRPC) may lead to osteoporosis, skeletal events, reduced quality of life, and even reduced overall survival (OS). Bone-modifying agents may prevent those events but their effect on cancer-control outcomes remains uncertain. Relying on our institutional tertiary-care database, we explored the effect of bone-modifying agents (bisphosphonates such as zoledronic acid and denosumab) on OS and progression-free survival in patients with mCRPC with at least 1 bone metastasis using Kaplan-Meyer estimates and Cox regression models. Of 420 patients with mCRPC, 60% received bone-modifying agents who were younger (68 vs 69 years), with more systemic treatment lines for mCRPC (3 vs 2), and a higher proportion of initial de novo metastatic disease (72% vs 62%, all ≤ .04) than patients without bone-modifying agents. In progression-free survival analyses, no significant differences were observed between both groups. In OS analyses, significant median OS differences were observed in favor of patients with bone-modifying agents (58 vs 45 months; hazard ratio [HR]: 0.66), even after multivariable adjustment (HR: 0.37; both ≤ .01). In bone-modifying agent-stratified analyses, 57% received denosumab vs 43% bisphosphonates, with a significantly higher rate of Eastern Cooperative Oncology Group status of ≥2 in the bisphosphonates group. In progression-free and OS analyses, no significant differences were observed between bisphosphonates and denosumab patients, with numerically better results in progression-free survival analysis for denosumab after adjusting for covariates. The cumulative rate of osteonecrosis of the jaw at any treatment time was 12% in both groups and significantly decreased over time. Real-world data suggest a relatively low administration rate of bone-modifying agents in patients with osseous mCRPC. However, real-world data also suggest an OS benefit when bone-modifying agents are used, even after controlling for possible confounding patient and tumor characteristics.
用于转移性去势抵抗性前列腺癌（mCRPC）的激素药物可能会导致骨质疏松、骨骼事件、生活质量下降，甚至总生存期（OS）缩短。骨改良药物可能会预防这些事件，但其对癌症控制结局的影响仍不确定。基于我们机构的三级医疗数据库，我们使用Kaplan-Meier估计法和Cox回归模型，探讨了骨改良药物（如唑来膦酸和地诺单抗等双膦酸盐类药物）对至少有1处骨转移的mCRPC患者的总生存期和无进展生存期的影响。在420例mCRPC患者中，60%接受了骨改良药物治疗，这些患者比未接受骨改良药物治疗的患者更年轻（68岁对69岁），接受mCRPC全身治疗的疗程更多（3个对2个），初始新发转移性疾病的比例更高（72%对62%，均≤0.04）。在无进展生存期分析中，两组之间未观察到显著差异。在总生存期分析中，即使经过多变量调整，也观察到接受骨改良药物治疗的患者的总生存期有显著差异（58个月对45个月；风险比[HR]：0.66），多变量调整后差异仍显著（HR：0.37；均≤0.01）。在按骨改良药物分层的分析中，57%的患者接受了地诺单抗治疗，43%的患者接受了双膦酸盐类药物治疗，双膦酸盐类药物治疗组中东部肿瘤协作组（ECOG）体能状态≥2的比例显著更高。在无进展生存期和总生存期分析中，双膦酸盐类药物治疗组和地诺单抗治疗组之间未观察到显著差异，在校正协变量后，地诺单抗治疗组在无进展生存期分析中的数值结果更好。两组在任何治疗时间的颌骨坏死累积发生率均为12%，且随时间显著下降。真实世界数据表明，骨改良药物在骨转移mCRPC患者中的使用率相对较低。然而，真实世界数据也表明，即使在控制了可能混淆的患者和肿瘤特征后，使用骨改良药物仍可带来总生存期获益。
