Prognostic significance of neutrophil-to-lymphocyte ratio in small cell lung cancer in the era of immunotherapy.

Abstract

e20129 Background: Cancer-related inflammation is evident in the peripheral blood as neutrophilia and/or lymphopenia. Previous studies have demonstrated inferior outcomes in patients with elevated neutrophil-to-lymphocyte ratios (NLR) in small cell lung cancer (SCLC). However, most of these studies were before the introduction of immunotherapy; the results were mixed, and it remains uncertain whether NLR possesses prognostic relevance even in the current era of immunotherapy. Methods: In this single-center retrospective observational study, we aimed to evaluate the prognostic significance of NLR in SCLC patients before and after the introduction of immunotherapy for SCLC. We chart reviewed all patients diagnosed with SCLC in our center from July 2010 to June 2013 (the “pre-immunotherapy era”) and from July 2020 to June 2023 (the “immunotherapy era”). Patients were categorized into two groups: high NLR (NLR ≥ 4) and low NLR (NLR < 4). We performed relevant statistical analyses, including Kaplan-Meier survival analysis, concentrating on the current immunotherapy era. Results: Between July 2010 and June 2013, 80 patients were diagnosed with SCLC. 36 (45.0%) patients had high NLR, and 55 (68.8%) had extensive-stage (ES) SCLC at diagnosis. 100% of them were smokers. Patients with high NLR had a significantly inferior median overall survival (OS) compared to those with low NLR (8.7 months versus 11.2 months, P = 0.01). Between July 2020 and June 2023, 90 patients were diagnosed with SCLC. The median age was 64.2 years. 53.3% were males, and 96.7% had a history of smoking. 46 (51.1%) patients had high NLR, and 66 (73.3%) had ES-SCLC at diagnosis. The median OS for all patients was 12.9 months (limited-stage = not reached, ES-SCLC = 10.5 months, P < 0.001). Patients with high NLR had a median OS of 12.5 months compared to 16.7 months in patients with low NLR (P = 0.35). Overall, a higher number of patients with high NLR had ES-SCLC compared to those with low NLR (82.9% vs. 60.2%, P < 0.01). Among patients with ES-SCLC, elevated NLR did not influence median OS (P = 0.37) or median progression-free survival (PFS) with immunotherapy (P = 0.60). Also, NLR on the day of starting immunotherapy did not influence PFS (P = 0.21) or OS (P = 0.27) with immunotherapy. Conclusions: Patients with ES-SCLC had a higher NLR, reflecting a higher tumor burden and more cancer-related inflammation. Although elevated NLR was associated with inferior survival outcomes in the pre-immunotherapy era, it did not hold similar prognostic significance in the current immunotherapy era. Elevated NLR did not significantly influence outcomes with immunotherapy either, highlighting the evolving role of immune therapies in overcoming traditional poor prognostic factors. This study highlights the need for larger prospective studies to determine if traditional prognostic factors, like NLR, still hold prognostic relevance in the era of immunotherapy.