The Pretreatment Neutrophil-to-Eosinophil Ratio Can Predict Immune-Related Adverse Events and Outcomes in Patients With Advanced Urothelial Carcinoma Treated With Immune Checkpoint Inhibitors

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.