INTRODUCTION: In metastatic renal cell carcinoma (mRCC), the bone is the second most common site of metastasis and is associated with increased morbidity and poorer quality of life. Bone-targeted therapies (BTTs) such as denosumab and zoledronic acid may prevent skeletal-related events (SREs). However, the benefit of BTTs in combination with tyrosine kinase inhibitors (TKIs) remains unclear. METHODS: We performed a retrospective chart review at the Urologic Cancer Centre for Research and Innovation. Patients with mRCC were included if they had bone metastases treated with TKIs between 2010 and 2017. Our primary outcome was overall survival (OS), defined as the time elapsed from clinical diagnosis of mRCC to death, and modelled using the Kaplan–Meier method. Secondary outcomes included the median time to SRE and the analysis of prognostic factors of OS using Cox proportional hazards regression. RESULTS: In total, 230 patients with mRCC were identified; of which, 46 had bone metastases treated with TKIs and were included in the study (TKI-only, n = 37; TKI + BTT, n = 9). In the TKI + BTT cohort, patients received either denosumab (n = 5) or zoledronic acid (n = 4). At the time of analysis, 63% of patients were deceased. We observed an OS trend favouring the TKI + BTT cohort (13.8 months [95% confidence interval {CI}: 12.3–15.2] vs. 29.6 months [95% CI: 7.2–51.9], hazard ratio [HR]: 1.66 (95% CI: 0.62–4.45), P = 0.31). When patients in the TKI + BTT cohort were stratified by type of therapy (denosumab or zoledronic acid), the median time to SRE was similar between the groups (4.2 months [95% CI: 2.28–6.14] vs. 2.2 months [95% CI: not available], P = 0.71]. On univariate or multivariate analysis, it was found that age, gender, comorbidities, International metastatic RCC database consortium (IMDC) prognostic group and pathologic tumour grade were not significant predictors of worse OS. Pathologic stage 3 or 4 was an independent predictor of worse OS (HR: 5.8, 95% CI: 1.41–24.03, P = 0.015). CONCLUSION: BTTs may have a continued role in the era of targeted therapy and immunotherapy. Further prospective data are required to validate our findings.

简介：在转移性肾细胞癌（mRCC）中，骨骼是第二个最常见的转移部位，并且与发病率增加和生活质量降低有关。地诺单抗和唑来膦酸等骨靶向疗法（BTT）可以预防骨骼相关事件（SRE）。但是，BTT与酪氨酸激酶抑制剂（TKI）结合的益处尚不清楚。方法：我们在泌尿外科癌症研究与创新中心进行了回顾性图表审查。如果mRCC患者在2010年至2017年之间接受了TKI的骨转移治疗，则将其包括在内。我们的主要结局是总体生存期（OS），定义为从mRCC临床诊断到死亡所经历的时间，并使用Kaplan-Meier方法进行建模。次要结果包括达到SRE的中位时间和使用Cox比例风险回归分析OS的预后因素。结果：总共鉴定出230例mRCC患者。其中46例接受了TKI治疗的骨转移，被纳入研究（仅TKI，n  = 37； TKI + BTT，n  = 9）。在TKI + BTT队列中，患者接受了denosumab（n = 5）或唑来膦酸（n  = 4）。在分析时，有63％的患者死亡。我们观察到倾向于TKI + BTT队列的OS趋势（13.8个月[95％置信区间{CI}：12.3–15.2]与29.6个月[95％CI：7.2-51.9]，危险比[HR]：1.66（95 ％CI：0.62-4.45），P  = 0.31）。当按治疗类型（地诺单抗或唑来膦酸）对TKI + BTT队列的患者进行分层时，两组间SRE的中位时间相似（4.2个月[95％CI：2.28-6.14]与2.2个月[95％]） CI：不可用]，P = 0.71]。在单因素或多因素分析中，发现年龄，性别，合并症，国际转移性RCC数据库联合会（IMDC）的预后组和病理性肿瘤分级不是OS恶化的重要预测指标。病理3或4期是OS恶化的独立预测因子（HR：5.8，95％CI：1.41-24.03，P  = 0.015）。结论： BTT可能在靶向治疗和免疫治疗时代继续发挥作用。需要进一步的前瞻性数据来验证我们的发现。