Pseudo-Progression and the Neutrophil-to-Lymphocyte Ratio in Non-Small Cell Lung Cancer Treated with Immune Checkpoint Inhibitors: A Case–Control Study

PURPOSE: Pseudo-progression (PsPD) is a rare phenomenon observed in <5% of cases of non-small cell lung cancer (NSCLC). This event is challenging for both clinicians and patients. Viable biomarkers to distinguish between PsPD and true progressive disease (TPD) are lacking. The aim of our study was to determine the correlation between PsPD and the neutrophil-to-lymphocyte ratio (NLR) in patients with NSCLC treated with immune checkpoint inhibitors (ICIs). PATIENTS AND METHODS: We retrospectively reviewed the clinical records of NSCLC patients treated with ICI monotherapy from December 2015 to October 2018 at Kobe University Hospital, Japan. Twenty-five patients were determined to have either PsPD (n =4) or TPD (n =21). We focused on longitudinal radiological images and NLRs. RESULTS: Here, we report four patients with PsPD. The pre- and post-treatment NLRs were significantly lower in patients with PsPD than in patients with TPD (p = 0.019 and p = 0.007, respectively). The receiver operating characteristic curve according to the pre- and post-treatment NLR showed areas under the curve of 0.82 and 0.94, respectively. The optimal cut-off values for pre- and post-treatment NLR were 4.1 and 3.2, respectively. The pre- and post-treatment NLRs were useful in distinguishing between PsPD and TPD. Both a pre-treatment NLR <4.1 and a post-treatment NLR <3.2 were significantly associated with longer overall survival compared to a pre-treatment NLR ≥4.1 (p < 0.001) and post-treatment NLR ≥3.2 (p = 0.004), respectively. CONCLUSION: The NLR could be a viable clue for distinguishing between PsPD and TPD. Patients with a high post-treatment NLR in this study all had TPD, suggesting that these subjects should be considered for an early transition to the next drug treatment regimen.