4.2.2. Salvage Surgery after Treatment with ICIs

Recently, the effectiveness of the PD-1 inhibitor pembrolizumab in patients with stage IV lung NSCLC was reported as the result of a phase III trial (KEYNOTE-407). The estimated 6-month OS rate was 80.2% with pembrolizumab administration. Moreover, the median PFS with pembrolizumab of 10.3 months (not reached) was superior to that with platinum doublet chemotherapy (6 months) [34].

Furthermore, ICI combined with chemotherapy for stage IV NSCLC was reported to significantly improve OS and PFS compared with chemotherapy alone as reported in phase III trials (KEYNOTE-189 [35,36] and KEYNOTE-407 [37]). The median OS and PFS were 15.9–22 months and 6.4–8.8 months, respectively. These survival benefits were consistent regardless of the level of programmed death-ligand 1 expression. Based on this evidence, ICI or ICI combined with chemotherapy is recommended as standard therapy for stage IV NSCLC without a driver mutation.

Although there have been few reports concerning salvage surgery after ICI, Bott retrospectively examined 19 patients who underwent lung resection after ICI for metastatic or unresectable cancer, including lung cancer (47%) and metastatic melanoma (37%). Of patients who underwent resection, R0 resection was achieved in 95% and 68% of patients with viable tumor remaining. Complications occurred in 32% of patients. The 2-year OS was 77% [38]. In NSCLC, the frequency of salvage surgery has been increasing in recent years, and with the spread of ICI, salvage surgery after ICI may increase in the future. Salvage surgery after ICI is possibly a feasible and effective treatment; however, to date, it has only been described in one case report [39]. It is necessary to accumulate further evidence regarding salvage surgery after ICI.

Although there is no evidence that salvage surgery after definitive therapy confers a survival benefit compared with other non-surgical radical therapy, here, we show selected studies regarding current standard first-line therapy for stage III/IV NSCLC and limited reports on salvage surgery (Table 1).


**Table 1.** Selected studies on salvage surgery and first-line therapy for stage III/IV NSCLC.

CRT: chemoradiotherapy, CT: chemotherapy, EGFR-TKI: epidermal growth factor receptor-tyrosine kinases inhibitor, ICI: immune-checkpoint inhibitor, mPFS: median progression-free survival, MST: median survival time, N.A.: not available, NSCLC: non-small cell lung cancer, OS: overall survival, Ref.: reference, RR: response rate, RT: radiotherapy, SS: salvage surgery, y: year.
