Surgical Removal of Residual Tumor Masses in Patients Undergoing Targeted Therapy for EGFR-Mutated Locally Advanced or Metastatic Lung Cancer.

Non-small cell lung cancer (NSCLC) patients with EGFR mutations usually receive continuous treatment with tyrosine kinase inhibitors (TKIs) until disease progression. We evaluated whether surgical excision of residual tumor masses offers a survival advantage when performed before progression on TKI therapy. We conducted a retrospective analysis of 230 patients with locally advanced or metastatic EGFR-mutated NSCLC who were treated with first-line EGFR TKI. Among these subjects, surgical intervention appeared technically feasible in 57 patients, 41 of whom underwent cytoreductive surgery while 16 were not operated for various reasons. Both surgically treated and nonsurgically treated patients received TKI until disease progression. The median duration of TKI treatment before surgery was 7.3 months. There was no perioperative mortality, while 8/41 (19.5%) patients experienced surgery-related complications. The median progression-free survival (PFS) and overall survival (OS) in the surgically treated group were 28.4 months and 46.9 months, respectively. These outcomes were significantly better than in patients with potentially resectable disease who did not undergo surgery (PFS: 15.4 months, p = 0.010; OS: 26.5 months, p = 0.015), or in subjects not amenable to cytoreduction (PFS: 19.0 months, p = 0.006; OS: 31.7 months, p = 0.001). Mutation analysis of residual tumor tissues revealed emerging TKI-resistant clones in 4 of 21 investigated patients. At the time of data cut-off, 12/41 (29%) surgically treated patients remained disease-free. In conclusion, surgical removal of residual tumor masses in EGFR-mutated NSCLC during response to TKI may confer a survival advantage.