Neutrophil-to-Lymphocyte Ratio (NLR) as a Predictive Biomarker in Advanced Hepatocellular Carcinoma Treated with First-Line Immunotherapy.

Abstract

Purpose: Hepatocellular carcinoma (HCC) is a globally prevalent malignancy with high mortality and limited predictive biomarkers. The neutrophil-to-lymphocyte ratio (NLR), a systemic inflammation marker, has been proposed as a prognostic tool. This study aimed to evaluate the association between baseline NLR and clinical outcomes in patients with advanced HCC treated with first-line immunotherapy.

Methods: We conducted a retrospective analysis of 58 consecutive patients with advanced HCC treated with atezolizumab plus bevacizumab or durvalumab plus tremelimumab at a Latin American cancer center between July 2020 and March 2025. Baseline NLR was calculated from pretreatment blood counts and dichotomized using a cut-off of 4. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method and compared using the log-rank test. Univariable and multivariable Cox regression models were applied to assess prognostic and predictive factors. The association between NLR and disease control rate (DCR) was evaluated using logistic regression.

Results: Among 58 patients, 15 (28.8%) had NLR ≥ 4. Median PFS was significantly shorter in patients with NLR ≥ 4 compared to those with NLR < 4 (2.3 vs. 8.2 months; p < 0.001). In multivariable analysis, NLR ≥ 4 remained independently associated with inferior PFS (HR 3.90; 95% CI, 1.83-8.33; p < 0.001). NLR was not associated with OS. Patients with NLR ≥ 4 had markedly lower odds of achieving disease control (OR 0.04; 95% CI, 0.002-0.28; p = 0.005).

Conclusion: Baseline NLR ≥ 4 is associated with inferior PFS and reduced DCR in patients with advanced HCC receiving immunotherapy. NLR may serve as a cost-effective predictive biomarker to inform immunotherapy strategy.