Prognostic Value of Circulating Tumor Cells and Cancer Associated Macrophage-Like Cells in Metastatic Non-Small Cell Lung Cancer Patients: A Retrospective Exploratory Analysis

ABSTRACT: Objectives: Although immune checkpoint inhibitors (ICIs) and targeted therapies have reshaped treatment non-small cell lung cancer (NSCLC) paradigms, prognosis remains poor for many patients due to delayed diagnosis and resistance mechanisms. Liquid biopsy offers a minimally invasive approach to monitoring tumor evolution. Among circulating biomarkers, circulating tumor cells (CTCs) and cancer-associated macrophage-like cells (CAM-Ls) may provide complementary prognostic insights. The study aimed to evaluate the prognostic role of CTC and CAM-Ls dynamic in metastatic NSCLC patients. Methods: We retrospectively analyzed 77 patients with metastatic NSCLC who underwent CTC and CAM-L evaluation via the CellSearchR system at baseline (T0) and after three months of first-line treatment (T1) including chemotherapy, targeted therapy, or ICIs. Survival outcomes were analyzed using Kaplan-Meier and Cox regression analyses. Results: Conversion to CTC-negative status at T1 was associated with improved outcomes, with median overall survival (OS) and progression-free survival (PFS) of 33 and 18 months, respectively, vs. 10 and 6 months in persistently positive patients (both p < 0.001). CTC negativity at T1 remained an independent prognostic factor for OS (HR: 6.68) and PFS (HR: 5.91, both p < 0.0001). CAM-L positivity at T1 also correlated with longer OS (30 vs. 12 months) and PFS (13 vs. 6 months, both p < 0.0001), particularly among ICI-treated patients. Combined CTC and CAM-L assessment further refined risk stratification. Conclusions: Dynamic monitoring of CTCs and CAM-Ls provides actionable prognostic information in metastatic NSCLC. CTC-negative status predicted longer OS and PFS, while CAM-L positivity at T1 was associated with improved outcomes, particularly in ICI-treated patients. Combined assessment of both biomarkers may directly inform therapeutic decision-making, through early detection of outcomes.