AbstractObjective:Although depression appears to be associated with worse survival from cancer, the underlying mechanisms of this association are unknown. Tumor epidermal growth factor receptor (EGFR) genotype is a known predictor of survival in metastatic non-small cell lung cancer (NSCLC) and appears to be associated with depression. We hypothesized that tumor EGFR genotype may account for a relationship between depression and survival in this population. We investigated this possible relationship in a cohort of patients with metastatic NSCLC, in which we had previously demonstrated an association between depression and worse survival.Method:A cohort of 151 patients with newly diagnosed metastatic NSCLC were enrolled and followed in a randomized controlled trial of early palliative care. At enrollment, 150 had depression assessed with the Patient Health Questionnaire-9 (PHQ-9), and categorical scoring for major depressive syndrome (MDS) was used for analyses. Patients with tumor tissue available underwent EGFR genotyping. Associations with survival were tested using Cox proportional hazards models, adjusting for potential confounders.Results:Twenty-one patients (14.0%) met criteria for MDS. Forty-four patients (29.3%) had EGFR genotyping, and 17 (38.6%) of these harbored EGFR mutations. Patients with EGFR mutations had significantly lower PHQ-9 scores (p = 0.03), and none met criteria for depression. EGFR mutations were significantly associated with superior survival (p = 0.02). When both depression and EGFR genotype were simultaneously entered into the model, only EGFR mutations remained significantly associated with survival (p = 0.02), and the effect of depression was attenuated.Significance of results:Depression is associated with worse survival in metastatic NSCLC, and this relationship may be at least partially explained by tumor EGFR genotype. Further study into whether depression could be associated with specific biologic properties of cancer that vary by genotype is warranted.