The impact of EGFR mutation status on outcomes in patients with resected stage I non-small cell lung cancers

Benjamin Izar, Lecia Sequist, Mihan Lee, Alona Muzikansky, Rebecca Heist, John Iafrate, Dora Dias-Santagata, Douglas Mathisen, Michael Lanuti
Annals of Thoracic Surgery 2013, 96 (3): 962-8

BACKGROUND: Mutations of the epidermal growth factor hormone receptor (EGFR) gene have been associated with improved treatment response and prognosis in advanced non-small lung cancer (NSCLC). However, their prognostic role in early-stage NSCLC is not well defined. In this study we sought to identify the pure prognostic role of EGFR mutation in patients with completely resected stage I NSCLC who received no adjuvant therapy.

METHODS: Mutation status was tested in treatment-naïve patients who had complete resection of stage I (T1-2aN0) NSCLC (from 2004 to 2011) using direct sequencing or multiplex polymerase chain reaction-based assay. Recurrence rates, disease-free survival, and overall survival were compared between EGFR-mutant and wild-type patients using Kaplan-Meier methods and Cox regression models.

RESULTS: Three hundred seven patients were included in this study; 62 harbored tumors with EGFR mutations and 245 had wild-type EGFR. Tumors in patients with EGFR mutations were associated with a significantly lower recurrence rate (9.7% versus 21.6%; p=0.03), greater median disease-free survival (8.8 versus 7.0 years; p=0.0085), and improved overall 5-year survival (98% versus 73%; p=0.003) compared with wild-type tumors. Lobectomy was the most frequently performed procedure, accounting for 209 of 307 operations. Among these patients, EGFR mutation was associated with superior overall survival (hazard ratio, 0.45; 95% confidence interval, 0.13 to 0.83; p=0.017), with an estimated 5-year survival of 98% versus 70%. The presence of EGFR mutation (p=0.026) and tumor size less than 2 cm (p=0.04) were identified as independent prognostic markers for disease-free survival, whereas age, sex, and smoking status were not.

CONCLUSIONS: Completely resected stage I EGFR mutation-positive NSCLC patients have a significant survival advantage compared with EGFR wild-type patients. Mutation of the EGFR gene is a positive prognostic marker in completely resected stage I NSCLC.

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