The outcomes of salvage surgery for non-small cell lung cancer after immune checkpoint inhibitor or targeted therapy treatment. A multi-center international real-life study

Objectives: In recent years, targeted therapy and immunotherapy have been demonstrated to improve survival in non-operable, non-small cell lung cancer (NSCLC) patients. The results of salvage lung resection in patients with initially unresectable advanced NSCLC after immune checkpoint inhibitor (ICI) or Target Therapy (TT) treatment remain unclear. This study aimed to define the outcomes of patients undergoing salvage surgery in a multi-center real-life setting. Methods: An international multicenter retrospective cohort study was conducted. Patients included in the study were judged inoperable, according to a multidisciplinary tumor board decision, before being submitted to ICI or TKI treatment. The rate of complications, the overall survival (OS), and progression-free survival (PFS) were compared. Crude and Multivariable-adjusted analysis were conducted. Results: Nighty-eight patients affected by NSCLC were included in the study. Most patients were female (N = 50–51 %), and the median age at surgery was 62 years. While ICI was performed in 29 patients (30 %), TT was done in 45 (46 %), and ICI plus chemotherapy in 24 (24 %). The inoperability was determined by metastatic disease in 43 cases (44 %), N2-N3 advanced disease in 18 (18 %), local invasiveness in 10 (10 %), a combination of local invasiveness and N-status in 26 (27 %), and other reasons in 1 case (1 %). Overall, the complication rate was 30 %, the mortality rate was 1 %, and the median LOS was 6 days. No residual lung disease (ypT0) was observed in 30 patients (31 %). The 5-year OS was 74 %, while the 5-year PFS was 44 %. Performing sublobar resections was an independent adverse prognostic factor in the multivariable analysis for survival (P < 0.01), while the pathological complete response (pCR) was an independent prognostic predictor of improved survival (P = 0.025). On multivariable analysis performing a sublobar resection (P < 0.01), an increasing ypT stage (P < 0.01), and postoperative therapy (P < 0.01) were independent prognostic predictors, correlating with impaired disease progression. Conclusions: Patients selected for Salvage Surgery after ICI or TT have reasonable post-operative and long-term outcomes. In this context, Salvage Surgery could be proposed in selected patients after a careful multidisciplinary evaluation.