Neutrophil-to-lymphocyte ratio as a prognostic biomarker in bladder cancer: A REMARK-guided secondary analysis of SWOG 8710.

Abstract

361 Background: Pre-operative risk stratification is a major challenge in bladder cancer (BC), and a biomarker is needed. Recent studies suggest baseline neutrophil-to-lymphocyte ratio (NLR) correlates with survival in BC, but these results are threatened by methodological limitations. We tested whether NLR is prognostic for overall survival (OS) in BC following principles detailed by the REMARK biomarker guidelines. Methods: SWOG 8710 was a randomized, phase III trial assessing radical cystectomy (RC) ± neoadjuvant chemotherapy (NAC). It enrolled 317 patients with T2-T4aN0 BC. Baseline NLR was calculated from prospectively-collected pre-treatment complete blood counts. We performed a secondary analysis on 230 patients with valid NLR who successfully completed RC (119 patients) or NAC + RC (111 patients). We evaluated the association of NLR with OS in univariable and multivariable Cox regression models, adjusting for pre-specified factors (age, gender, T-stage, lymphovascular invasion [LVI], and treatment received). Model assumptions of linearity and proportional hazards were checked. We estimated an 80% power to detect a hazard ratio (HR) of ≥ 1.11 for death with each unit increase in NLR at α = 0.05. We addressed missing values via multiple imputation and defined OS from date of treatment to death. Results: There were complete data for all covariates except a small portion ( < 7%) of LVI values. Median baseline NLR was 2.7 (IQR 2.0-4.1), and NLR was not significantly associated with any other covariate. During a median follow-up of 18.6 years, there were 172 deaths. On multivariable analysis, older age (HR 1.05, 95% CI [1.04-1.07], P < 0.001) and treatment with RC alone (HR 1.39, 95% CI [1.03-1.88], P = 0.03) were associated with worse OS. Baseline NLR was not associated with OS in either univariable (HR = 1.03, 95% CI [0.97 – 1.10], P = 0.30) or multivariable models (HR = 1.04, 95% CI [0.98 – 1.11], P = 0.24). Conclusions: In contrast to previous studies, this analysis of prospectively-collected trial data suggests baseline neutrophil-to-lymphocyte ratio is not prognostic for OS in patients with muscle-invasive bladder cancer.