Salvage surgery for initially unresectable advanced-stage non-small cell lung cancer after chemotherapy with immune-checkpoint inhibitor: a narrative review

Background and Objective: Recently developed immune checkpoint inhibitors (ICIs) have demonstrated a strong anti-tumor effect when used with cytotoxic chemotherapy agents. Consequently, a significant proportion of stage III–IV inoperable advanced lung cancers have been downstaged, and a few select patients have undergone salvage surgery to resect loco-regional residual or regrowth tumors. However, those surgical outcomes are not clarified due to the rarity. In this narrative review, we summarize the clinical features and postoperative outcomes of salvage surgery for advanced-stage lung cancer after ICI treatment. Methods: On August 1, 2025, we searched PubMed for cases published between January 2019 and June 2025, using the search terms “salvage lung cancer surgery and/or immune checkpoint inhibitor” or “salvage lung cancer surgery and/or immunotherapy”. We included case presentations or original manuscripts from English literature and excluded review articles, surgeries for biopsy, incomplete resections and non-pulmonary resections. We defined “salvage surgery” as surgery for patients with initially unresectable advanced-stage lung cancer, where the residual downstaged tumor lesions or recurrent cancer lesions are resected after chemotherapy or chemoradiotherapy with an ICI, such as pembrolizumab, durvalumab, nivolumab or atezolizumab. Key Content and Findings: We found 101 articles, from which we selected 46 patients. The median age was 64 years old (range, 44–82 years old). The histology was adenocarcinoma (18 cases), squamous cell carcinoma (22 cases), large cell carcinoma (2 cases), adenosquamous cell carcinoma (1 case), and other (3 cases). The pretreatment clinical stage was III (27 cases) and IV (19 cases). The postoperative complications (all grade) occurred in 13 out of 46 cases, and the 30-day mortality was 1 out of 46 cases. The chemotherapy response rate was 9 out of 25 cases for a pathological complete response. The postoperative pathological stage distribution was ypStage 0/I/II/III/IV/NA: 9/17/8/7/3/2. Documented postoperative survival time ranged from 1 to 43 months. Conclusions: Salvage lung resection after treatment with an ICI for initially unresectable lung cancer is a feasible and acceptable procedure, based on perioperative surgical results. However, close, optimal patient selection with a multidisciplinary team and cautious perioperative management are required. Further long-term follow-up data is expected.