4.2.1. Salvage Surgery after Treatment with TKIs

For patients with stage IV NSCLC, chemotherapy resulted in only approximately a 7% improvement in 1-year survival compared with survival with best supportive care [28]. Compared with chemotherapy, EGFR-TKI administration results in a high response rate in patients with *EGFR* mutation-positive lung cancer; in particular, osimertinib has a response rate of 80% [29]. Among patients in whom TKI has a dramatic effect, salvage surgery for local residual/recurrent lesions is a possible treatment strategy.

Hishida et al. reported nine patients with stage IV NSCLC who underwent tumor resection after gefitinib administration. Surgery was performed for local tumor persistence, recurrence, or re-growth after treatment with gefitinib (duration of administration, 2–36 months), and the median OS after resection was 32 months. The median recurrence-free period was reported to be 6 months [30]. In another study, Hishida et al. reported the long-term outcome of 4 patients who underwent pulmonary resection for residual/regrown primary lesion of NSCLC treated with gefitinib. Recurrence was observed in three of four cases; however, all of them survived for 5 years or more after surgery. The remaining case continued to receive TKI administration for 4 years after surgery without cancer relapse [31]. Based on these reports, although no large-scale data are available, it is quite possible that salvage surgery after EGFR-TKI can be expected to have local control effects. A similar significance of salvage surgery has been reported in a case report on the use of ALK inhibitors for NSCLC with *ALK* gene translocations [32].

Recently, the effectiveness of osimertinib as a postoperative adjuvant therapy for resectable *EGFR* mutation-positive NSCLC was reported as the result of a phase III trial (ADAURA Clinical Trials, NCT02511106) [33]. In that trial, disease-free survival was significantly longer among patients who were administered osimertinib than among those who received placebo (90% versus 44%). It was unclear whether TKI should be continued after salvage surgery following treatment using TKI. However, considering the result of the ADAURA trials, it is possible that the prognosis will be improved if TKI is continued even after complete resection by salvage surgery.
