Abstract
<title>Abstract</title> <p>Background: The prognostic significance of the geriatric nutritional risk index (GNRI) in muscle-invasive bladder cancer (MIBC) treated with neoadjuvant chemotherapy (NAC) followed by radical cystectomy remains unclear. We evaluated associations between pretreatment GNRI, survival, skeletal muscle change, and immune-related features in post-NAC cystectomy specimens. Methods: We retrospectively analyzed 51 patients with MIBC who received platinum-based NAC followed by radical cystectomy between 2011 and 2022. GNRI was calculated at NAC initiation and dichotomized at 98. Overall survival (OS) and progression-free survival (PFS) were evaluated using Kaplan-Meier and Cox regression analyses. Exploratory analyses assessed skeletal muscle index change and PD-L1, CD8/CD4 ratio, tumor-cell IDO1, and tumor-cell CD73 expression. Causal mediation analysis explored whether PD-L1 mediated the association between GNRI and OS. Results: High GNRI remained independently associated with favorable OS in multivariable analysis (hazard ratio 0.30, 95% confidence interval 0.10–0.92; p < 0.05), although PFS did not differ significantly. Skeletal muscle index change was similar between groups. PD-L1 positivity was more frequent in the high-GNRI group (69.0% vs 23.5%; p < 0.01), whereas CD8/CD4 ratio, IDO1, and CD73 were not associated with GNRI. Mediation analysis did not support a significant indirect effect through PD-L1. Conclusions: Pretreatment GNRI was independently associated with OS and with PD-L1 positivity in residual post-NAC tumors. Its prognostic association appeared largely independent of PD-L1-mediated effects.</p>