Prognosis for patients with metastatic bladder carcinoma (mBC) remains limited and in need of novel therapies. We retrospectively analyzed medical records of 43 patients with platinum-refractory metastatic bladder cancer (mBC) who participated in one or more phase 1 trials of various investigational therapies. Patients' tumors or circulating tumor DNA were analyzed by next generation sequencing. Median progression-free survival was 4.2 months, median overall survival was 9.6 months, and the overall response rate was 17.5%. TP53, ERBB2, PI3KCA, FGFR3 and ARID1A alterations were detected in 66%, 29%, 27%, 24%, and 22% of all patients, respectively. Alterations in FGFR3 were almost mutually exclusive of TP53. More than half (64%) of patients with an FGFR alt received an FGFR inhibitor, 67% of which, achieved disease control. Among patients with urothelial carcinoma histology, those harboring a TP53 alteration had a shorter median PFS compared to those whose tumors carry wild-type TP53. The reverse relationship was observed in patients harboring an FGFR alteration. Implications: Patients with platinum-refractory mBC derive clinical benefit from participating in early phase clinical trials and their survival outcomes correlate with the genetic profile of the tumor.

中文翻译：

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转移性膀胱癌早期临床试验参与者的分子谱预测患者预后

转移性膀胱癌 (mBC) 患者的预后仍然有限，需要新疗法。我们回顾性分析了 43 名铂难治性转移性膀胱癌 (mBC) 患者的医疗记录，这些患者参与了一项或多项各种研究疗法的 1 期试验。通过下一代测序分析患者的肿瘤或循环肿瘤 DNA。中位无进展生存期为 4.2 个月，中位总生存期为 9.6 个月，总缓解率为 17.5%。分别在 66%、29%、27%、24% 和 22% 的所有患者中检测到 TP53、ERBB2、PI3KCA、FGFR3 和 ARID1A 改变。FGFR3 中的改变几乎与 TP53 相互排斥。超过一半 (64%) 的 FGFR alt 患者接受了 FGFR 抑制剂，其中 67% 实现了疾病控制。在组织学尿路上皮癌患者中，与肿瘤携带野生型 TP53 的患者相比，携带 TP53 改变的患者的中位 PFS 较短。在 FGFR 改变的患者中观察到相反的关系。意义：铂类难治性 mBC 患者从参与早期临床试验中获得临床益处，并且他们的生存结果与肿瘤的遗传特征相关。