Prediction of immune checkpoint inhibitor therapy in urothelial carcinoma: integrated analysis of molecular patterns and clinical factors

Magyar onkologia Pub Date : 2026-03-12 Epub Date: 2026-01-10

Melinda Hermann-Váradi

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Abstract

Aim: To identify clinicopathological and molecular factors influencing immune checkpoint inhibitor efficacy in urothelial carcinoma (UC).

Methods: We analyzed >200 patients with locally advanced or metastatic UC treated with pembrolizumab or atezolizumab. Gene expression profiling was performed on 100 tumors, and baseline and on-treatment serum soluble PD-L1 (sPD-L1) levels were measured. Integrated clinicopathological- molecular survival model was developed.

Results: Objective response rate (ORR) and overall survival (OS) were comparable to clinical trials. Poor ECOG status, metastases, low hemoglobin, and Bellmunt risk factors independently predicted shorter OS. Gene expression analysis identified 23 genes associated with OS and additional genes linked to response; PSMB10 showed validated prognostic and predictive value. Neuronal and TCGA-luminal infiltrated subtypes had the best outcomes, and high neuronal signatures correlated with longer OS. Elevated baseline sPD-L1 predicted poor OS.

Conclusions: Integrating clinical and molecular biomarkers improves survival stratification and may refine immunotherapy selection in UC.

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预测免疫检查点抑制剂治疗尿路上皮癌：分子模式和临床因素的综合分析

目的：探讨影响免疫检查点抑制剂治疗尿路上皮癌疗效的临床病理及分子因素。方法：我们分析了bb200例局部晚期或转移性UC患者，这些患者接受了派姆单抗或阿特唑单抗治疗。对100个肿瘤进行基因表达谱分析，并测量基线和治疗时血清可溶性PD-L1 （sPD-L1）水平。建立综合临床病理-分子生存模型。结果：客观缓解率（ORR）和总生存期（OS）与临床试验相当。较差的ECOG状态、转移、低血红蛋白和bellmont危险因素独立预测较短的OS。基因表达分析鉴定出23个与OS相关的基因和其他与应答相关的基因；PSMB10显示了有效的预后和预测价值。神经元和tcga -腔浸润亚型预后最好，神经元特征高与生存期长相关。基线sPD-L1升高预示较差的OS。结论：结合临床和分子生物标志物可改善UC患者的生存分层，并可细化免疫治疗的选择。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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Magyar onkologia

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