Predictive and prognostic value of preoperative serum tumor markers is EGFR mutation-specific in resectable non-small-cell lung cancer

BACKGROUND The predictive and prognostic value of carcinoembryonic antigen (CEA), cytokeratin-19 fragments (Cyfra21-1), squamous cell carcinoma antigen (SCCA) and neuron-specific enolase (NSE) has been investigated in non-small-cell lung cancer (NSCLC) patients. However, few studies have directly focused on the association between these markers and epidermal growth factor receptor (EGFR) mutation status or mutation subtypes. PATIENTS AND METHODS We retrospectively analyzed 1016 patients with stage I-IIIA NSCLC who underwent complete resection between 2008 and 2012. Correlations between serum tumor marker levels and EGFR mutations and survival parameters were analyzed and prognostic factors were identified. RESULTS Cyfra21-1 levels (P = 0.032 for disease-free survival [DFS]; P < 0.001 for overall survival [OS]) and clinical stage were identified as independent predictive and prognostic factors in EGFR-mutated adenocarcinoma patients. CEA levels (P < 0.001 for DFS; P = 0.002 for OS) and clinical stage were independently predictive and prognostic in EGFR wild-type adenocarcinoma patients. Further stratification analysis revealed that in EGFR exon 19 deletion adenocarcinomas, elevated Cyfra21-1 was an independent prognostic factor (P = 0.002). Within the Leu858Arg substitution subgroup, increased CEA (P = 0.005) and clinical stage were predictive factors of DFS, while elevated CEA (P = 0.005) and Cyfra21-1 (P = 0.027) were independent prognostic factors. CONCLUSIONS Cyfra21-1 and CEA exhibit different predictive and prognostic values between EGFR-mutated and wild-type adenocarcinomas, as well as between EGFR mutation subtypes. The prognostic impact of preoperative serum tumor markers should be evaluated together with EGFR mutation status.