成纤维细胞生长因子受体改变对卡介苗免疫治疗和非卡介苗免疫治疗的高级别非肌肉浸润性膀胱癌的预后和预测价值。

Prognostic and Predictive Value of Fibroblast Growth Factor Receptor Alterations in High-grade Non-muscle-invasive Bladder Cancer Treated with and Without Bacillus Calmette-Guérin Immunotherapy.

机构信息

Department of Urology, Caritas St. Josef Medical Center, University of Regensburg, Regensburg, Germany.

Institute of Pathology, University of Erlangen-Nuremberg, Erlangen, Germany.

出版信息

Eur Urol. 2022 Jun;81(6):606-614. doi: 10.1016/j.eururo.2022.02.028. Epub 2022 Mar 26.

DOI:10.1016/j.eururo.2022.02.028

PMID:35351346

Abstract

BACKGROUND

Limited data are available on the prognostic and predictive value of fibroblast growth factor receptor alterations (FGFRa) relative to clinical outcomes in patients with non-muscle-invasive bladder cancer (NMIBC).

OBJECTIVE

To determine whether FGFRa may be clinically useful in stratifying for treatment response in a real-world cohort of patients with pT1 NMIBC treated and untreated with bacillus Calmette-Guérin (BCG) instillation therapy.

DESIGN, SETTING, AND PARTICIPANTS: A pooled dataset of matched clinical and genomic data (1992-2015) for pT1 NMIBC patients was assessed by the Bladder Cancer Research Initiative for Drug Targets in Germany consortium.

OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS

Key efficacy outcomes were recurrence-free survival (RFS), progression-free survival (PFS), and disease-specific survival (DSS), which were estimated by Kaplan-Meier analysis, with hazard ratios calculated using a multivariate Cox proportional-hazard model.

RESULTS AND LIMITATIONS

In this retrospective study of 263 patients with high-grade NMIBC, at a median follow-up of 63 mo, 32% showed recurrence and 15% progressed to muscle-invasive bladder cancer. FGFRa were found in 43% of patients, including 39% mutations and 5.7% fusions. FGFRa were associated with lower rates of concomitant carcinoma in situ. Among patients with or without FGFRa, there was no significant difference in PFS, RFS, and DSS in those who were BCG treated or BCG naive, or in the overall population. Limitations include the retrospective design from a single-center setting.

CONCLUSIONS

In patients with high-risk NMIBC, FGFRa were frequently observed. Patients with FGFRa who often exhibit recurrence/relapse after BCG treatment have a high unmet need.

PATIENT SUMMARY

Our retrospective study suggests that fibroblast growth factor receptor alterations (FGFRa) occur frequently in non-muscle-invasive bladder cancer (NMIBC). Outcomes were similar with or without FGFRa in patients with NMIBC, both overall and for standard bacillus Calmette-Guérin (BCG) treatment.

摘要

背景

关于成纤维细胞生长因子受体改变（FGFRa）相对于非肌肉浸润性膀胱癌（NMIBC）患者临床结局的预后和预测价值，数据有限。

目的

确定 FGFRa 是否可用于对接受和未接受卡介苗（BCG）膀胱内灌注治疗的 pT1NMIBC 患者的治疗反应进行分层，从而具有临床意义。

设计、设置和参与者：德国膀胱癌药物靶点研究倡议联盟对 pT1NMIBC 患者的匹配临床和基因组数据（1992-2015 年）进行了汇总数据集评估。

观察指标和统计分析

主要疗效结局是无复发生存率（RFS）、无进展生存（PFS）和疾病特异性生存（DSS），通过 Kaplan-Meier 分析进行评估，使用多变量 Cox 比例风险模型计算风险比。

结果和局限性

在这项对 263 例高级别 NMIBC 患者的回顾性研究中，中位随访 63 个月时，32%的患者出现复发，15%进展为肌层浸润性膀胱癌。在 43%的患者中发现 FGFRa，包括 39%的突变和 5.7%的融合。FGFRa 与同时存在原位癌的比例较低有关。在有或没有 FGFRa 的患者中，在接受或未接受 BCG 治疗的患者中，在总体人群中，PFS、RFS 和 DSS 无显著差异。局限性包括来自单一中心的回顾性设计。