Assessment of the Efficacy and Clinical Utility of Different Circulating Tumor Cell (CTC) Detection Assays in Patients with Chemotherapy-Naïve Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC)

• Main Authors: Maria A. Papadaki, Ippokratis Messaritakis, Oraianthi Fiste, John Souglakos, Eleni Politaki, Athanasios Kotsakis, Vassilis Georgoulias, Dimitrios Mavroudis, Sofia Agelaki
• Format: Article
• Language: English
• Published: MDPI AG 2021-01-01
• Series: International Journal of Molecular Sciences
• Subjects: liquid biopsy; circulating tumors cells; non-small cell lung cancer; CellSearch system; CEACAM5mRNA; prognostic biomarkers
• Online Access: https://www.mdpi.com/1422-0067/22/2/925

We herein investigated the detection frequency and clinical relevance of circulating tumor cells (CTCs) in chemotherapy-naïve stage IIIB/IV non-small cell lung cancer (NSCLC), by using the CellSearch and real-time CEACAM5mRNA assays. Blood samples from 43 patients were obtained at different time points during first-line chemotherapy. CellSearch revealed the detection of ≥1 CTCs in 41.9%, 40.9%, and 16.7% of patients at baseline, post-1st, and post-2nd treatment cycle, respectively, and of ≥5 CTCs in 11.6%, 9.1%, and 5.6%, respectively. CEACAM5mRNA+ CTCs were detected in 29.3% and 16% of patients pre- and post-treatment, respectively. The positivity concordance between the two assays was 2.2%. CTC-detection by CellSearch (≥5 CTCs: <i>p</i> = 0.004), CEACAM5mRNA (<i>p</i> = 0.010), or by any assay (<i>p</i> = 0.000) was associated with disease progression. Reduced survival was demonstrated for patients harboring ≥5 CTCs (progression-free survival; PFS: <i>p</i> = 0.000; overall survival; OS: <i>p</i> = 0.009), CEACAM5mRNA+ CTCs (PFS: <i>p</i> = 0.043; OS: <i>p</i> = 0.039), and CTCs by any assay (PFS: <i>p</i> = 0.005; OS: <i>p</i> = 0.006, respectively). CTC-detection by any assay independently predicted for increased risk of relapse (hazard ratio; HR: 3.496; <i>p</i> = 0.001) and death (HR: 2.866; <i>p</i> = 0.008). CellSearch-positivity either pre-, post-1st, or post-2nd cycle, was predictive for shorter PFS (<i>p</i> = 0.036) compared to negativity in all time points. Persistent CEACAM5mRNA-positivity pre- and post-treatment was associated with reduced PFS (<i>p</i> = 0.036) and OS (<i>p</i> = 0.026). In conclusion, CTC detection and monitoring using the CellSearch and CEACAM5mRNA assays provides valuable and complementary clinical information for chemo-naïve advanced or metastatic NSCLC.