Genetic Analysis and Operative Outcomes in Patients with Oncogene-Driven Advanced NSCLC Treated with Cytoreductive Surgery as a Component of Local Consolidative Therapy.

Abstract

Simple SummaryThe efficacy of the local consolidative therapy in lung cancer has been reported previously, however, those studies described the utility of the radiation therapy rather than of surgery. Furthermore, those studies included either no or few patients with oncogene-driven NSCLC, which has distinct biological properties and treatment options. Surgery is the most reliable method of tumor removal that allows detailed examinations of resected tissue, such as comprehensive genetic analysis. This retrospective study for the first time reports the operative outcomes and the benefit of cytoreductive surgery in TKI-treated cases of oncogene-driven locally advanced or metastatic NSCLC in parallel with the genetic analysis of the tumor.Most patients with oncogene-driven advanced non-small cell lung cancer (NSCLC) demonstrate recurrence because of the developing targeted therapy resistance. In this retrospective study, we assessed the efficacy of surgical local consolidative treatment by analyzing the operative outcomes and genetic data in 44 patients who underwent pulmonary resection for stage IIIB/C–IV NSCLC after targeted therapy. The initial mutations were in the EGFR (n = 32), ALK (n = 11), and ROS1 (n = 1) genes. The median interval from the initiation of tyrosine kinase inhibitor (TKI) therapy immediately before the surgery to the actual operation was 9.8 months. Operative mortality was absent. Four patients showed complete remission. The median follow-up period after TKI therapy initiation was 23.1 months. The Kaplan–Meier survival analysis showed that the 2-year failure-free survival and overall survival rates from the initiation of TKI were 70.8% and 95.0%, respectively. During the follow-up period, two patients died and 15 suffered from disease progression. Among the 32 patients with EGFR mutations, 12 showed additional mutations, and targeted agents were replaced in nine patients after the operation. We conclude that pulmonary resection for advanced NSCLC after targeted therapy is feasible, and the surgical specimens could be used for planning further targeted therapy.