Circulating and tumor microenvironment immunomarkers associate with immunotherapy efficacy in advanced bladder urothelial carcinoma: an exploratory multicenter study integrating genomic and immunophenotypic profiling

Aims To elucidate the efficacy-predictive values of immunomarkers in both peripheral blood and tumor tissue in patients with advanced bladder-urothelial-carcinoma (aBUC) undergoing first-line immunotherapy.Patients and methods In previously untreated aBUC, T-cell subclusters and PD-L1 expression were determined using immunohistochemistry, and genetic profiling was conducted using cSMART 2.0 sequencing. Peripheral blood immunomarkers were assessed both at baseline and prior to the second immunotherapy cycle for dynamic analysis.Results Lower baseline neutrophil-to-lymphocyte ratio (NLR) was associated with better disease-control (p = 0.048) and improved overall survival (p = 0.028), and NLR was an independent predictive factor (HR = 3.40, 95%-CI = 1.10-10.49, p = 0.034). Patients with better disease-control had lower monocyte-to-lymphocyte ratio (MLR) (p = 0.020). An early-decrease in platelet-to-lymphocyte ratio (PLR) at the second immunotherapy-cycle in patients with inferior baseline-PLR was linked to a longer progression-free survival (p = 0.040). Patients with higher NLR at Cycle 1 or 2 of immunotherapy had lower CD8+ lymphocyte level or tumor-mutation-burden (TMB), and those with higher PLR had higher PD-L1 expression in the tumor-microenvironment. A significant negative correlation was identified between NLR and TMB in primary tumors (r = -0.919, p = 0.027).Conclusions Circulating immunomarkers at baseline and/or second cycle of immunotherapy were linked to the microenvironment immunomarkers, and exploratorily showed associations with disease control and/or survival in aBUC undergoing first-line immunotherapy.