Abstract
Introduction Currently, treatment regimens incorporating immune checkpoint inhibitors (ICIs) are the standard of care for locally advanced or metastatic urothelial carcinoma (la/mUC). This study aimed to investigate the association between the neutrophil-to-eosinophil ratio (NER) and the occurrence of immune-related adverse events (irAEs) as well as treatment outcomes. Methods This multicenter retrospective study examined patients with la/mUC treated with ICIs between January 2017 and December 2022. Results A total of 243 patients with la/mUC were analyzed: 207 who received pembrolizumab after chemotherapy and 36 who received avelumab as maintenance therapy. In the overall cohort, the median progression-free survival (PFS) from the initiation of ICIs was 5.3 months, while the median overall survival (OS) was 23.9 months. Grade 2 or higher irAEs were observed in 72 patients (29.6%), whereas grade 3 or higher events were identified in 31 patients (12.8%). In univariate analysis, the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), NER, and systemic immune-inflammation index (SII) at the initiation of treatment were identified as predictive factors for grade 2 or higher irAEs. In multivariate analysis, NER was found to be an independent predictive factor. Patients with NER of ≤44 at the initiation of treatment had a significantly higher incidence of grade 2 or higher irAEs than those with NER >44 (36.7% vs. 20.2%; p=0.009). However, they also exhibited significantly longer PFS (p=0.003) and OS (p<0.001). Conclusions In la/mUC, pretreatment NER may serve as a predictive marker for irAEs and treatment outcomes in patients receiving ICIs.