Patterns of Spread and Prognostic Implications of Lung Cancer Metastasis in an Era of Driver Mutations

Background: In the present study, we examined the pattern of metastatic spread in patients with advanced non-small-cell lung cancer (NSCLC) and the effect of EGFR mutations. Methods: Patients were identified from a provincial cancer registry, and individual medical records were reviewed. Patients were included if they had stage IV NSCLC and underwent diagnostic EGFR mutation testing. Patients were divided into EGFR mutation-positive (EGFR+) and EGFR wild type (WT) cohorts. The primary endpoint was the cumulative incidence for each metastatic site: lung, bone, brain, liver, adrenal glands, distant nodes, and other. Cumulative incidence curves were estimated using a competing-risks method. The secondary outcome was survival. Results: Of the 543 identified patients, 121 (22.3%) tested as EGFR+, and 422 (77.7%) tested as EGFR WT. The incidence of brain (39.2% vs. 28.2%, p = 0.038) and lung (61.2% vs. 51.0%, p = 0.048) metastasis was higher in the EGFR+ cohort than in the EGFR WT cohort. In the EGFR+ cohort, a higher incidence of liver metastasis was associated with the exon 21 mutation subtype than with the exon 19 deletion subtype [23% vs. 7%, p < 0.01; hazard ratio (HR): 3.47]. Median survival was significantly longer for the EGFR+ cohort than for the EGFR WT cohort (22.4 months vs. 7.9 months, p < 0.001). In multivariable analysis, brain (HR: 1.73), liver (HR: 1.69), and bone (HR: 1.89) metastases were associated with worse survival. Conclusions: Rates of lung and brain metastases are higher in EGFR mutation carriers, even when adjusted for differences in survival. Brain, liver, and bone metastases are independent negative prognostic factors for survival.