Abstract

BACKGROUND:

Outcomes of patients with metastatic urothelial carcinoma (mUC) with early bone metastases (eBM) vs no early bone metastases (nBM) have not thoroughly been described in the age of immuno-oncology.

OBJECTIVE:

To compare survival and other clinical outcomes in patients with eBM and nBM.

METHODS:

We used a multi-institutional database of patients with mUC treated with systemic therapy. Demographic, metastatic site, treatment patterns, and clinical outcomes were recorded. Wilcoxon rank-sum, chi-square tests were performed. Survival was estimated by Kaplan-Meier method; multivariable Cox analysis was performed.

RESULTS:

We identified 270 pts, 67%men, mean age 69±11 years. At metastatic diagnosis, 27%had≥1 eBM and were more likely to have de novo vs. recurrent metastases (42%vs 19%, p < 0.001). Patients with eBM had shorter overall survival (OS) vs. those with nBM, (6.1 vs 13.7 months, p < 0.0001). On multivariable analysis, eBM independently associated with higher risk of death, HR = 2.52 (95%CI: 1.75–3.63, p < 0.0001). OS was shorter for patients with eBM who received initial immune checkpoint inhibitor vs platinum-based chemotherapy, (1.6 vs 9.1 months, p = 0.02). Patients with eBM received higher opioid analgesic doses compared to patients with nBM and received quantitatively more palliative radiation.

CONCLUSIONS:

Patients with mUC and eBM have poorer outcomes, may benefit less from anti-PD-1/PD-L1 therapy and represent an unmet need for novel therapeutic interventions. Dedicated clinical trials, biomarker validation to assist in patient selection, as well as consensus on reporting of non-measurable disease are required.

中文翻译：

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早期骨转移与转移性尿路上皮癌的更糟糕结果相关

 抽象的

 背景：

在免疫肿瘤学时代，伴有早期骨转移 (eBM) 与无早期骨转移 (nBM) 的转移性尿路上皮癌 (mUC) 患者的结局尚未得到彻底描述。

 客观的：

比较 eBM 和 nBM 患者的生存率和其他临床结果。

 方法：

我们使用了接受全身治疗的 mUC 患者的多机构数据库。记录人口统计学、转移部位、治疗模式和临床结果。进行了 Wilcoxon 秩和、卡方检验。通过Kaplan-Meier法估计生存率；进行多变量 Cox 分析。

 结果：

我们确定了 270 名患者，其中 67% 为男性，平均年龄 69±11 岁。在转移诊断时，27% 的 eBM ≥1，并且更有可能出现新发转移，而不是复发转移（42% vs 19%， p < 0.001）。与 nBM 患者相比，eBM 患者的总生存期 (OS) 较短（6.1 个月与 13.7 个月， p < 0.0001）。在多变量分析中，eBM 与较高的死亡风险独立相关，HR = 2.52（95%CI：1.75–3.63， p < 0.0001）。与铂类化疗相比，接受初始免疫检查点抑制剂的 eBM 患者的 OS 更短（1.6 个月 vs 9.1 个月， p = 0.02）。与 nBM 患者相比，eBM 患者接受了更高的阿片类镇痛剂量，并且接受了更多的姑息性放射治疗。

 结论：

mUC 和 eBM 患者的预后较差，从抗 PD-1/PD-L1 治疗中获益较少，并且对新型治疗干预措施的需求未得到满足。需要专门的临床试验、生物标志物验证来协助患者选择，以及就报告不可测量的疾病达成共识。