Background: Immune checkpoint inhibitors (ICIs) improve overall survival (OS) in advanced/metastatic urothelial cancer (a/mUC) patients. Preliminary evidence suggests a prognostic role of inflammatory biomarkers in this setting. We aimed to develop a disease-specific prognostic inflammatory index for a/mUC patients on ICIs. Methods: Fifteen variables were retrospectively correlated with OS and progression-free survival (PFS) in a development (D, n = 264) and a validation (V, n = 132) cohort of platinum-pretreated a/mUC pts receiving ICIs at L2 or further line. A nomogram and inflammatory prognostic index (U-IPI) were developed. The index was also tested in a control cohort of patients treated with chemotherapy only (C, n = 114). Results: The strongest predictors of OS were baseline platelet/lymphocyte (PLR) and neutrophil/lymphocyte (NLR) ratios, and lactate dehydrogenase (LDH), NLR, and albumin changes at 4 weeks. These were used to build the U-IPI, which can distinctly classify patients into good or poor response groups. The nomogram scoring is significant for PFS and OS (p< 0.001 in the D, V, and combined cohorts) for the immunotherapy (IO) cohort, but not for the control cohort. Conclusions: The lack of a baseline systemic inflammatory profile and the absence of early serum inflammatory biomarker changes are associated with significantly better outcomes on ICIs in a/mUC pts. The U-IPI is an easily applicable dynamic prognostic tool for PFS and OS, allowing for the early identification of a sub-group with dismal outcomes that would not benefit from ICIs, while distinguishing another that draws an important benefit.
背景：免疫检查点抑制剂（ICIs）可改善晚期/转移性尿路上皮癌（a/mUC）患者的总生存期（OS）。初步证据表明，炎症生物标志物在此背景下具有预后作用。本研究旨在为接受ICIs治疗的a/mUC患者开发一种疾病特异性预后炎症指数。 方法：在开发队列（D，n = 264）和验证队列（V，n = 132）中，回顾性分析了15个变量与接受二线或更后线ICIs治疗的铂类预处理a/mUC患者OS和无进展生存期（PFS）的相关性。构建了列线图和炎症预后指数（U-IPI）。该指数也在仅接受化疗的对照组患者（C，n = 114）中进行了测试。 结果：OS的最强预测因素是基线血小板/淋巴细胞比值（PLR）和中性粒细胞/淋巴细胞比值（NLR），以及第4周时的乳酸脱氢酶（LDH）、NLR和白蛋白变化。这些指标被用于构建U-IPI，该指数可将患者明确区分为反应良好组和反应不良组。列线图评分在免疫治疗（IO）队列中对PFS和OS具有显著意义（在D、V及合并队列中p < 0.001），但在对照组中不显著。 结论：缺乏基线全身炎症特征以及早期血清炎症生物标志物无变化，与a/mUC患者接受ICIs治疗获得显著更好的预后相关。U-IPI是一种易于应用的动态预后工具，可用于评估PFS和OS，能够早期识别出无法从ICIs中获益且预后不良的亚组，同时区分出另一类能从中获得重要获益的亚组。
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