Assessing the prognosis of metastatic or recurrent non-small cell lung cancer in the era of modern systemic therapies: a multivariable analysis of 343 patients treated in Poland.

Background: Prognostic factor assessment in metastatic or recurrent non-small cell lung cancer (NSCLC) is based primarily on older studies from the chemotherapy era or modern trials evaluating the safety and efficacy of specific treatment regimens. However, studies that compare prognostic factors across immunotherapy, molecularly guided therapy, and chemotherapy within the same real-world context remain scarce. This gap is addressed by the present study which aims to retrospectively evaluate prognostic factors for overall survival in patients treated with diverse systemic therapies.

Methods: The analysis included 343 patients with metastatic or recurrent NSCLC treated between 2006 and 2022. Treatment consisted of immune checkpoint inhibitors (ICI) in 176 patients, epidermal growth factor receptor (EGFR) inhibitors in 72, ALK/ROS inhibitors in 25 and chemotherapy in 70. Adenocarcinoma was diagnosed in 210 patients, squamous-cell cancer in 110 and other types of NSCLC in 23. Several host and tumor-related variables evaluated before therapy were categorized (mainly according to their median values) and used to construct a multivariate Cox survival model. Therapies were classified (ranked) according to the effectiveness as assessed in a univariate analysis.

Results: Hemoglobin concentration [hazard ratio (HR) 0.50, P<0.001], sex (HR 0.63, P=0.0009), T stage (HR 1.38, P=0.001), pathology (HR 1.43, P=0.15), performance status (HR 1.60, P=0.002), platelet count (HR 1.46, P=0.005), lymphocyte/neutrophil ratio (HR 0.69, P=0.008), and tumor volume (HR 1.45, P=0.008) significantly influenced OS in a univariable analysis. Treatment also influenced overall survival, with a median survival times of 1.57, 1.90, 0.60 and 0.80 years for ICI, anti EGFR, ALK/ROS and chemotherapy, respectively. Multivariable analysis revealed a significant and independent influence of T stage, hemoglobin concentration, performance status, lymphocyte/neutrophil ratio, and treatment on survival. Treatment, while significant, appeared as a relatively weak independent prognosticator of survival, compared to the other variables. For sensitivity assessment, several options of the basic analysis were performed without altering, however, the qualitative outcomes of the basic analysis.

Conclusions: The outcome of this study strongly encourages the routine use of readily available independent prognostic factors for survival such as T stage, hemoglobin concentration, patient performance status, and lymphocyte/neutrophil ratio, regardless of systemic treatment selected for therapy of patients with metastatic or recurrent NSCLC.