Neutrophil-to-Lymphocyte Ratio as a Potential Biomarker in Patients with Localized Urothelial Carcinoma Treated with Chemotherapy - Expert Commentary

A standard of care treatment for patients with muscle-invasive bladder cancer (MIBC) is cisplatin-based neoadjuvant chemotherapy (NAC) followed by radical cystectomy. Since this treatment modality is associated with significant toxicity, predicting patient response to treatment can prevent unnecessary adverse events and delays to effective treatment.

Accordingly, efforts to discover practical, reliable, and cost-effective biomarkers have intensified. Some studies have indicated that systemic inflammatory response biomarkers, such as neutrophil-to-lymphocyte ratio (NLR), are potentially useful in predicting treatment outcomes as they may reflect tumor microenvironment status. von Deimling et al. tested whether NLR could be used as a predictor of prognosis in patients with urothelial carcinoma.

The researchers carried out a retrospective analysis of treatment parameters, clinical outcomes, and pre-treatment blood samples from 404 patients (collected from a multicenter database). Calculated pre-treatment NLR was high in 41.8% of patients. This was significantly associated with a higher probability of adverse pathologic features such as advanced tumor stage and lymph node metastases. High NLR was also associated with a reduced probability of complete and partial responses. In a predictive model that accounted for various factors, such as treatment regimen, age, and clinical tumor stage, the addition of pre-treatment NLR as a variable increased the model’s accuracy in predicting complete or partial response. This was also observed in a subgroup analysis for patients with lymph node involvement.

The median follow-up time was 49 months, during which 33.7% of patients experienced recurrence and 25% died of urothelial carcinoma. The five-year relapse-free survival, cancer-specific survival, and overall survival rates were 62.2%, 69.9%, and 62.5%, respectively. In a Cox regression analysis, high NLR was significantly associated with shorter rates for all three survival measures. Among the patients with lymph node involvement subgroup, the median follow-up was 40 months, during which 55.2% experienced recurrence and 41.4% died of urothelial carcinoma. Within this subgroup, the five-year relapse-free survival, cancer-specific survival, and overall survival rates were 36.9%, 52.2%, and 49.2%, respectively. Elevated pre-treatment NLR is an independent risk factor for lymph node metastasis and response to cisplatin-based NAC. However, it did not meaningfully improve the C-statistic of models that relied on either clinicopathologic variables to predict survival outcomes. Longitudinal prospective studies in which NLR is analyzed over time in a large cohort of patients and across different treatment modalities will be potentially informative in this setting.

Written by: Bishoy M. Faltas, MD, Director of Bladder Cancer Research, Englander Institute for Precision Medicine, Weill Cornell Medicine
Reference:

  1. von Deimling M, Schuettfort VM, D'Andrea D, et al. Predictive and Prognostic Role of the Neutrophil-to-Lymphocyte Ratio in Muscle Invasive Bladder Cancer Treated With Neoadjuvant Chemotherapy and Radical Cystectomy [published online ahead of print, 2023 Jan 26]. Clin Genitourin Cancer. 2023;S1558-7673(23)00031-9. doi:10.1016/j.clgc.2023.01.008
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