The impact of EGFR mutation status on outcomes in patients with resected stage I non-small cell lung cancers.
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.
Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA.
Benjamin
B
Izar
Lecia
L
Sequist
Mihan
M
Lee
Alona
A
Muzikansky
Rebecca
R
Heist
John
J
Iafrate
Dora
D
Dias-Santagata
Douglas
D
Mathisen
Michael
M
Lanuti
D000367:Age Factors; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000401:mortality* / Q000601:surgery; D015331:Cohort Studies; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000235:genetics* / Q000401:mortality* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation; D009361:Neoplasm Invasiveness / Q000473:pathology; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000401:mortality; D009367:Neoplasm Staging; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D018570:Risk Assessment; D012737:Sex Factors; D018709:Statistics, Nonparametric; D016019:Survival Analysis
D014408:Biomarkers, Tumor; D066246:ErbB Receptors
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