Circulating tumor cells in lung cancer are prognostic and predictive for worse tumor response in both targeted- and chemotherapy.

BACKGROUND: It is unknown whether the presence of circulating tumor cells (CTC), a known prognostic factor, influences treatment outcome. We investigated whether baseline CTC in non-small cell lung cancer (NSCLC) patients treated with tyrosine kinase inhibitors (TKI) or chemotherapy was associated with response to therapy. METHODS: We included consecutive advanced NSCLC patients, stratified by therapy. Before treatment the number of CTC was measured by CellSearch. Tumor response rates, progression free survival (PFS) and overall survival (OS) in patients with and without CTC at baseline were compared. RESULTS: We included 86 patients (34 treated by TKI). Response rates of patients with CTC were lower than in patients without CTC (OR =0.22, P<0.01, adjusted for performance score and smoking status). In both treatment groups, the difference in response rates between patients with and without CTC was similar (TKI response: 25% with CTC versus 73% without CTC, chemotherapy response: 35% versus 51% respectively, interaction P=0.17). CTC was associated with a worse PFS [hazard ratio (HR) =2.0, 95% confidence interval (CI): 1.2-3.2, P=0.01] and OS (HR =1.7, 95% CI: 1.1-2.8, P=0.03) after adjustment for performance score and stage. The association remained significant after adding tumor response to the model (PFS: HR =1.9, 95% CI: 1.0-3.0, P=0.01, OS: HR =1.6, 95% CI: 1.0-2.6, P=0.05). No significant interaction between CTC presence and therapy was observed (P=0.42 for PFS and P=0.83 for OS). CONCLUSIONS: Presence of CTC in advanced NSCLC patients is associated with low response rates, shorter PFS and OS, independent of the received therapy.