Resected Non-small Cell Lung Cancer Research Articles

Recent Noteworthy Studies in Thoracic Oncology.

In this paper, we review recent prospective surgical studies on resectable esophageal and lung cancer. A narrative literature review was performed using the terms 'resectable esophageal cancer' and 'multimodal therapy' and 'resectable non-small cell lung cancer'. Prospective surgical trials performed from 2010 to 2023 were identified and analyzed. gov was queried for ongoing studies. The studies on esophageal cancer demonstrate the benefits of neoadjuvant chemoradiation, compared with surgery alone, and the emerging role of immunotherapy as part of induction and adjuvant treatment protocols. The selected studies on lung cancer demonstrate the evolving role of sublobar resection for patients with peripheral node-negative clinical stage IA1 disease and the developing role of neoadjuvant and adjuvant immunotherapy for patients with stage II-IIIA disease. The methods of treating patients with resectable esophageal or lung cancer are changing. Efforts to limit patient morbidity and optimize tumor treatment before surgery are increasingly being pursued and these approaches will likely continue to evolve as tumor biology and long-term pharmacologic mechanisms of action become clearer. Personalized medicine strategies that are based on tumor characteristics and the host genetic profile remain on the horizon, not yet ready for adoption in routine clinical practice.

Regularity and correlation analysis of regional lymph node metastasis in nonoperative patients with non-small cell lung cancer based on positron emission tomography/computed tomography images

BackgroundDefinitive concurrent chemoradiotherapy (CCRT) is the standard treatment for locally advanced, inoperable non-small cell lung cancer (NSCLC). Previous studies have mainly focused on examining local failure and recurrence patterns after surgery and the principles of lymph node metastasis (LNM) in surgical candidates with NSCLC. However, these studies were just only able to guide postoperative radiotherapy (PORT) and the patterns of LNM in patients with resected NSCLC was inadequate to represent that in locally advanced inoperable NSCLC patients for guiding target volume delineation of CCRT. In this study, we aimed to analyze the metastasis regularities and establish the correlations between different lymph node levels in NSCLC patients without any intervention using positron emission tomography/computed tomography (PET/CT) images.MethodsOverall, 358 patients with N1–N3 NSCLC admitted in our hospital between 2018 and 2022 were retrospectively analyzed. The diagnosis of metastatic lymph nodes was reviewed and determined using the European Organization for Research and Treatment of Cancer standard and the standardized value of the PET/CT examination. Univariate and multivariate analysis were performed to investigate the correlations between the different levels were evaluated by using of the chi-square test and logistic regression model.ResultsThe lymph nodes with the highest metastasis rates in patients with left lung cancer were in order as follows: 10L, 4L, 5, 4R, and 7; while in those with right lung cancer they were 10R, 4R, 7, 2R, and 1R. Notably, we found left lung patients were more likely to have contralateral hilar, mediastinal and supraclavicular lymph nodes involved, and the right lung group exhibited a higher propensity for ipsilateral mediastinum and supraclavicular lymph node invasion. Furthermore, correlation analysis revealed there were significant correlative patterns in the LNM across different levels.ConclusionsThis study elucidated the patterns of primary LNM in patients with NSCLC who had not undergone surgery (without any treatment interventions) and the correlations between lymph node levels. These findings were expected to provide useful reference for target volume delineation in definitive concurrent chemoradiotherapy in locally advanced NSCLC patients.

Spatial profiling of METex14-altered NSCLC under tepotinib treatment: Shifting the immunosuppressive landscape

MET inhibitors have demonstrated efficacy in treating patients with non-small cell lung cancer (NSCLC) harboring METex14 skipping alterations. Advancements in spatial profiling technologies have unveiled the complex dynamics of the tumor microenvironment (TME), a crucial factor in cancer progression and therapeutic response.This study uses spatial profiling to investigate the effects of the MET inhibitor tepotinib on the TME in a case of locally advanced NSCLC with a METex14 skipping alteration. A patient with resectable stage IIIB NSCLC, unresponsive to neoadjuvant platinum-based chemotherapy, received tepotinib following the detection of a METex14 skipping alteration. Paired pre- and post-treatment biopsies were subjected to GeoMx Digital Spatial Profiling using the Cancer Transcriptome Atlas and immune-related protein panels to evaluate shifts in the immune TME.Tepotinib administration allowed for a successful lobectomy and a pathological downstaging to stage IA1. The TME was transformed from an immunosuppressive to a more permissive state, with upregulation of antigen-presenting and pro-inflammatory immune cells. Moreover, a marked decrease in immune checkpoint molecules, including PD-L1, was noted. Spatial profiling identified discrete immune-enriched clusters, indicating the role of tepotinib in modulating immune cell trafficking and function. Tepotinib appears to remodel the immune TME in a patient with METex14 skipping NSCLC, possibly increasing responsiveness to immunotherapy.Our study supports the integration of genetic profiling into the management of early and locally advanced NSCLC to guide personalized, targeted interventions. These findings underscore the need to further evaluate combinations of MET inhibitors and immunotherapies.

Sublobar resection for early-stage non-small cell lung cancer and current advances with immunotherapy in multimodality treatment of resectable non-small cell lung cancer

Sublobar resection for early-stage non-small cell lung cancer and current advances with immunotherapy in multimodality treatment of resectable non-small cell lung cancer

Resectable Non-Small Cell Lung Cancer Heterogeneity and Recurrence Assessed by Tissue Next-Generation Sequencing Genotyping and Circulating Tumor Cell EZH2 Characterization

IntroductionNon-small cell lung cancer (NSCLC) is the most common type of lung neoplasm. Despite surgical resection, it has a high relapse rate, accounting for 30–55% of all cases. Next-generation sequencing (NGS) based on a customized gene panel and the analysis of circulating tumor cells (CTCs) can help identify heterogeneity, stratify high-risk patients, and guide treatment decisions. In this descriptive study involving a small prospective cohort, we focus on the phenotypic characterization of CTCs, particularly concerning EZH2 expression (a member of the Polycomb Repression Complex 2), as well as on the mutation profiles of the tissue using a customized gene panel and their association with poor outcomes in NSCLC. MethodsIsolation and characterization of EZH2 on CTCs were evaluated before surgical resection (CTC1) and one month after surgery (CTC2) in resectable NSCLC patients. Targeted NGS was performed using a customized 50-gene panel on tissue samples from a subset of patients. Results76 patients with resectable NSCLC were recruited. The top mutated genes in the cohort included TP53, FLT1, MUC5AC, EGFR, and NLRP3. Pair of genes that had mutually exclusive mutations was TP53-RIN3, and pairs of genes with co-occurring mutations were CD163-TLR4, FGF10-FOXP2, ADAMTSL3-FLT1, ADAMTSL3-MUC5AC and MUC5AC-NLRP3. CTCs decreased significantly between the two time points CTC1 and CTC2 (p<0.0001), and CTCs+ patients with high EZH2 expression had an 87% increased risk of death (p=0.018). ConclusionsIntegrating molecular profiling of tumors and CTC characterization can provide valuable insights into tumor heterogeneity and improve patient stratification for resectable NSCLC.

A Meta-Analysis of Efficacy and Safety of Neoadjuvant Immunotherapy Plus Chemotherapy for Resectable Non-Small Cell Lung Cancer.

Neoadjuvant immunotherapy plus chemotherapy has ushered in a new era for surgical treatment for patients with NSCLC. This study aimed to examine the efficacy and safety of neoadjuvant immunotherapy plus chemotherapy in NSCLC. Eligible studies were identified from PubMed, Embase, Web of Science, Cochrane Library, ClinicalTrials.gov, and conference meeting abstracts. The endpoints included major pathological response (MPR), complete pathological response (pCR), surgical resection rate, R0 resection, treatment-related adverse events (TRAEs), severe adverse events (SAEs), surgical complications, treatment discontinuation, surgical delay, and treatment-related death. Stata 18 software was used for statistical analysis, and p < 0.05 was considered statistically significant. Twenty-two studies including a total of 1108 patients were eligible for this study. Among the patients who received neoadjuvant immunotherapy plus chemotherapy, the pooled MPR rate was 51% (95% CI [0.44-0.58]), and pCR rate was 34% (95% CI [0.28-0.40]). The pooled surgical resection rate was 85% (95% CI [0.81-0.89]), and the pooled R0 rate was 94% (95% CI [0.91-0.96]). The pooled rate of pathological tumor downstaging was 84% (95% CI [0.79-0.88]), and the pooled rate of pathological nodal downstaging was 38% (95% CI [0.23-0.57]). During the treatment of neoadjuvant immunotherapy plus chemotherapy with or without surgery, the pooled rate of TRAEs (any grade) was 84% (95% CI [0.73-0.91]), and the pooled rate of SAEs was 29% (95% CI [0.21-0.38]). Surgical complications pooled rate was 25% (95% CI [0.14-0.41]). The pooled rate of treatment discontinuation (11%, 95% CI [0.09-0.13]), surgical delay (3%, 95% CI [0.02-0.05]), and treatment-related death (2%, 95% CI [0.02-0.03]) were conducted. Neoadjuvant immunotherapy plus chemotherapy provides a high pathological response, surgical resection rate, R0 resection rate, and pathological downstage rate and has a low risk of increasing the incidence of SAEs, surgical complications, treatment discontinuation, surgical delay, and treatment-related death. The validation of prospective and large sample studies is needed to confirm this conclusion.

EP.07C.09 Neoadjuvant Chemoimmunotherapy (CIT) In Resectable Non-Small Cell Lung Cancer (NSCLC): Real-World Treatment Patterns and Surgical Outcomes

EP.07C.09 Neoadjuvant Chemoimmunotherapy (CIT) In Resectable Non-Small Cell Lung Cancer (NSCLC): Real-World Treatment Patterns and Surgical Outcomes

The CheckMate 816 trial: a milestone in neoadjuvant chemoimmunotherapy of nonsmall cell lung cancer.

Advancements in immunotherapy in the perioperative setting have revolutionised the treatment of resectable nonsmall cell lung cancer (NSCLC). Here we present the methodology and results of the clinical trial CheckMate 816 demonstrating the benefit of neoadjuvant therapy with nivolumab plus chemotherapy compared with chemotherapy alone. Furthermore, this article discusses the implications for future practice in resectable NSCLC and the need for future research.

EP.07G.05 Maximum Standardized Uptake Value and Cell-Free DNA to Predict Adjuvant Therapy in Resectable Non-Small Cell Lung Cancer

EP.07G.05 Maximum Standardized Uptake Value and Cell-Free DNA to Predict Adjuvant Therapy in Resectable Non-Small Cell Lung Cancer

What is the role of perioperative immunotherapy and chemotherapy in stage III resectable non-small cell lung cancer?

What is the role of perioperative immunotherapy and chemotherapy in stage III resectable non-small cell lung cancer?

EP.07C.10 Real-World Outcomes of Patients Treated with Neoadjuvant Immunotherapy for Resectable Non-Small Cell Lung Cancer

EP.07C.10 Real-World Outcomes of Patients Treated with Neoadjuvant Immunotherapy for Resectable Non-Small Cell Lung Cancer

Perioperative chemotherapy and nivolumab in non-small-cell lung cancer (NADIM): 5-year clinical outcomes from a multicentre, single-arm, phase 2 trial

Perioperative immunotherapy improves short-term outcomes in resectable non-small-cell lung cancer (NSCLC). We now report 5-year survival from the NADIM trial to assess its long-term benefit. NADIM was a multicentre, single-arm, phase 2 trial conducted across 18 hospitals in Spain. Patients were aged 18 years or older, had an Eastern Cooperative Oncology Group performance status of 0 or 1, and had histologically or cytologically confirmed, treatment-naive, resectable stage IIIA NSCLC (American Joint Committee on Cancer, 7th edition criteria). The neoadjuvant treatment consisted of three cycles of intravenous paclitaxel (200 mg/m2) and carboplatin (area under the curve 6 mg/mL per min) with nivolumab (360 mg). After surgery, 1 year of adjuvant treatment with intravenous nivolumab monotherapy was administered (240 mg every 2 weeks for 4 months, followed by 480 mg every 4 weeks for 8 months). The primary endpoint was 24-month progression-free survival, with 5-year progression-free survival and overall survival as secondary endpoints, assessed in the intention-to-treat population (ie, all patients who received neoadjuvant treatment). Toxicity profile was also assessed as a secondary endpoint. This trial is registered at ClinicalTrials.gov (NCT03081689) and is complete; this is the final report of the trial. Between April 26, 2017, and Aug 25, 2018, 51 patients were assessed for eligibility, of whom 46 comprised the intention-to-treat population (34 [74%] male and 12 [26%] female, median age 63 years [IQR 58-70]). Follow-up was concluded at 60 months (data cutoff July 11, 2023; median follow-up 60·0 months [IQR 60·0-60·0]). 5-year progression-free survival in the intention-to-treat population was 65·0% (95% CI 49·4-76·9), and overall survival was 69·3% (53·7-80·6). Disease progression occurred in 11 (24%) patients; 14 (30%) patients died, including nine (20%) from disease relapse and five (11%) from non-tumour-related causes. Treatment-related adverse events (TRAEs) of grade 3 or worse occurred in 14 (30%) of 46 patients during neoadjuvant treatment and in seven (19%) of 37 during adjuvant treatment. The most common grade 3 or worse TRAEs were increased lipase and febrile neutropenia (three [7%] each) during neoadjuvant treatment, and elevated serum lipase (four [7%]) and elevated serum amylase (three [8%]) during adjuvant treatment. Serious TRAEs included elevated serum lipase and neutropenia (one [2%] each) during neoadjuvant treatment, and elevated serum lipase (one [3%]) during adjuvant treatment. No treatment-related surgery delays, deaths, or unexpected long-term toxicities were reported. Perioperative chemoimmunotherapy showed a promising long-term benefit with no concerning safety data, reinforcing its use in resectable stage IIIA NSCLC. Bristol-Myers Squibb, Spanish Ministry of Science, Instituto de Salud Carlos III, European Union.

EP.07C.16 Real-World Outcomes of Patients with Resectable Early-Stage Non-Small Cell Lung Cancer Treated with Neoadjuvant Chemoimmunotherapy

EP.07C.16 Real-World Outcomes of Patients with Resectable Early-Stage Non-Small Cell Lung Cancer Treated with Neoadjuvant Chemoimmunotherapy

P1.03D.01 Efficacy and Biomarker Analysis of Neoadjuvant Toripalimab Plus Chemotherapy in Resectable Stage IIB-IIIB Non-Small Cell Lung Cancer (NSCLC)

P1.03D.01 Efficacy and Biomarker Analysis of Neoadjuvant Toripalimab Plus Chemotherapy in Resectable Stage IIB-IIIB Non-Small Cell Lung Cancer (NSCLC)

The relationship between sarcopenia and metabolic parameters of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) and the prognostic value of sarcopenia in early-stage non-small cell lung cancer.

Patients with lung cancer face a heightened risk of developing sarcopenia. Despite this known risk, the impact of sarcopenia on the long-term prognosis of lung cancer patients, specifically concerning progression-free survival (PFS) and overall survival (OS), remains unclear. The primary objective of our study was to examine the correlation between metabolic parameters derived from 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) and sarcopenia, as well as the prognostic value of sarcopenia in patients with surgically resected early-stage non-small cell lung cancer (NSCLC). In this retrospective cross-sectional study, we analyzed 187 NSCLC patients who underwent 18F-FDG PET/CT at the First Affiliated Hospital of Soochow University between March 2019 and October 2023. Patients were divided into two groups based on the presence (n=46) or absence (n=141) of sarcopenia. The correlation between sarcopenia, metabolic parameters, and patient characteristics was evaluated using chi-square and Mann-Whitney U tests. Survival analyses, including PFS and OS, were conducted using Kaplan-Meier analysis and Cox proportional hazards regression. Based on sarcopenia, metabolic parameters and patient characteristics, patients were classified into high-risk (n=28), intermediate-risk (n=121), and low-risk (n=38) groups. Our analysis identified gender, body mass index (BMI), psoas Hounsfield unit (HU), and maximum standardized uptake value of the psoas major muscle (SUVmax-Muscle) as independent predictors of sarcopenia (P<0.05 for all). A nomogram model, utilizing these parameters, was constructed to predict sarcopenia. Survival analysis further demonstrated that total lesion glycolysis [hazard ratio (HR) =2.499; 95% confidence interval (CI): 2.014-3.267; P=0.016], sarcopenia (HR =3.323; 95% CI: 1.748-6.316; P<0.001), and programmed death ligand-1 (PD-L1) expression (HR =0.093; 95% CI: 0.012-0.698; P=0.021) emerged as independent predictors of OS in early-stage NSCLC. Notably, patients categorized as high-risk, characterized by elevated total lesion glycolysis, presence of sarcopenia, and PD-L1 positivity, exhibited a significantly poorer prognosis compared to the intermediate-risk (P<0.05) and low-risk groups (P<0.05). Our findings indicated an inverse relationship between SUVmax-Muscle or psoas HU with the incidence of sarcopenia in NSCLC patients. Additionally, total lesion glycolysis, sarcopenia, and PD-L1 expression were identified as independent prognostic factors for OS in early-stage NSCLC. The risk stratification model, incorporating total lesion glycolysis, sarcopenia, and PD-L1 expression, assumed a pivotal role in guiding personalized therapy decisions and post-treatment monitoring.

Evidence from resected early-stage non-small cell lung cancer with EGFR mutation: a literature review.

Non-small cell lung cancer (NSCLC) in early-stages (I-IIIA) with epidermal growth factor receptor (EGFR) mutation may have specific epidemiological, clinical characteristics and treatment implications. This review aims to summarise the available evidence on these particularities, especially focusing on patient characteristics, treatment outcomes and safety with EGFR-tyrosine-kinase inhibitor (TKI). An exhaustive search of international bibliographic databases, as well as in abstracts of communications from major international congresses was performed for evidence related to EGFR-mutated NSCLC or early-stage NSCLC published in English before December 31st, 2023. Early-stage NSCLC with EGFR mutation presents with a variable incidence depending on geographical aspects. The clinical, radiological and molecular features differ slightly from both early-stage NSCLC without EGFR mutation and advanced NSCLC with EGFR mutation. Adjuvant treatment with the third-generation EGFR-TKI osimertinib has led to improvements in disease-free survival and overall survival (OS) in these patients, representing a practice changing and a new standard of care in clinical practice. No new safety signals have been reported with EGFR-TKI in the adjuvant setting. Clinical trials are ongoing to explore new therapeutic options in the adjuvant and neoadjuvant setting as well as the optimal duration of adjuvant osimertinib. Detection of EGFR mutation in early-stage NSCLC is an important goal due to the different characteristics and additional therapeutic options that improve patient outcomes and follow-up.

Histopathologic pattern and molecular risk stratification are associated with prognosis in patients with stage IB lung adenocarcinoma.

The benefit of adjuvant therapy remains controversial in completely resected (R0) stage IB non-small cell lung cancer (NCLSC) patients. In this study, we aimed to explore potential prognostic factors in stage IB NSCLC patients. This study included 215 patients with R0 stage IB lung adenocarcinoma (LUAD) (tumor size: 3-4 cm). DNA sequencing was performed with surgical samples of 126 patients using a panel of 9 driver genes. The molecular risk stratification was assessed by a 14-gene quantitative polymerase chain reaction assay. Among the 215 patients, 67.9% had micropapillary/solid (MIP/SOL)-predominant tumors. Epidermal growth factor receptor (EGFR) mutations were detected in 75 of 126 patients (59.5%). MIP/SOL tumors harbored less common EGFR mutations than the other histologic patterns (50.6% vs. 79.5%, P=0.003). Molecular risk stratification was successfully assessed in 99 patients, of whom 37.4%, 26.3%, and 36.4% were high, intermediate, and low risk, respectively. The MIP/SOL pattern was associated with shorter disease-free survival (DFS) [hazard ratio (HR) =2.16, 95% confidence interval: 1.28-3.67; P=0.01]. The molecular high-risk patients had shorter DFS than the low- (HR =2.93, P=0.01) and intermediate-risk patients (HR =2.35, P=0.06). The prognostic value of molecular risk stratification was also significant in the MIP/SOL subset (median DFS high-risk: 45 months, low and intermediate risk: not reached; P=0.03). Our study showed that both the MIP/SOL pattern and molecular high-risk category were adverse prognostic factors in stage IB NSCLC patients. Our results suggest that combining histologic classification and molecular risk stratification may help to identify the subset of patients with poor prognosis.

Elevated origin recognition complex subunit 6 expression promotes non-small cell lung cancer cell growth

Exploring novel targets for non-small cell lung cancer (NSCLC) remains of utmost importance. This study focused on ORC6 (origin recognition complex subunit 6), investigating its expression and functional significance within NSCLC. Analysis of the TCGA-lung adenocarcinoma database revealed a notable increase in ORC6 expression in lung adenocarcinoma tissues, correlating with reduced overall survival, advanced disease stages, and other key clinical parameters. Additionally, in patients undergoing surgical resection of NSCLC at a local hospital, ORC6 mRNA and protein levels were elevated in NSCLC tissues while remaining low in adjacent normal tissues. Comprehensive bioinformatics analyses across various cancers suggested that ORC6 might play a significant role in crucial cellular processes, such as mitosis, DNA synthesis and repair, and cell cycle progression. Knocking down ORC6 using virus-delivered shRNA in different NSCLC cells, both primary and immortalized, resulted in a significant hindrance to cell proliferation, cell cycle progression, migration and invasion, accompanied by caspase-apoptosis activation. Similarly, employing CRISPR-sgRNA for ORC6 knockout (KO) exhibited significant anti-NSCLC cell activity. Conversely, increasing ORC6 levels using a viral construct augmented cell proliferation and migration. Silencing or knockout of ORC6 in primary NSCLC cells led to reduced expression of several key cyclins, including Cyclin A2, Cyclin B1, and Cyclin D1, whereas their levels increased in NSCLC cells overexpressing ORC6. In vivo experiments demonstrated that intratumoral injection of ORC6 shRNA adeno-associated virus markedly suppressed the growth of primary NSCLC cell xenografts. Reduced ORC6 levels, downregulated cyclins, and increased apoptosis were evident in ORC6-silenced NSCLC xenograft tissues. In summary, elevated ORC6 expression promotes NSCLC cell growth.

Ten-year survival outcomes of video-assisted thoracic surgery vs. open major lung resection for stage I-III non-small cell lung cancer: a large cohort study in China.

Despite the widespread adoption of video-assisted thoracoscopic surgery (VATS) for major lung resection, the 10-year long-term survival outcomes of non-small cell lung cancer (NSCLC) treated with VATS compared with open major lung resection is lacking. The purpose of this study was to analyze the short- and long-term outcomes of VATS vs. open major lung resection for NSCLC. The perioperative outcomes and long-term survival of p-stage I-III NSCLC patients who underwent major lung resection via VATS vs. open major lung resection in the Western China Lung Cancer Database (WCLCD) between May 2006 and June 2018 were studied using propensity score matching (PSM). Of the 10,167 patients who underwent surgery for lung malignancies, 6,405 patients with stage I-III NSCLC were included in the study, including 4,224 in the VATS group and 2,181 in the open group. PSM resulted in 1,487 patients in both the VATS and open groups. The patients were matched by patient demographics, Charlson comorbidity index (CCI), tumor histology and TNM stage. Compared with open surgery, major lung resection via VATS resulted in less blood loss (median: 50 vs. 100 mL, P<0.001) and a shorter postoperative hospital stay (7.6±6.0 vs. 8.6±4.9 days, P<0.001) but higher total hospital costs (52.5±21.2 vs. 45.0±16.4 kRMB, P<0.001). The matched cohort showed that patients who underwent major lung resection via VATS had better overall survival (OS) and recurrence-free survival (RFS) than did patients who underwent major lung resection via open surgery (5-year survival: 64.9% vs. 57.7%, P<0.001; 5-year RFS: 50.3% vs. 45.3%, P=0.003). Patients who underwent VATS had a better 10-year OS rate (47.8% vs. 42.6%). According to the subgroup analysis, patients with stage II NSCLC who underwent major lung resection via VATS had better OS and RFS (OS: P<0.001; RFS: P=0.004), while there were no significant differences in OS or RFS between stage I and III NSCLC patients. Major lung resection via the VATS should be the preferred surgical option for stage I-III NSCLC patients due to its superior long-term survival outcome and advantages of less blood loss and shorter postoperative hospital stays.

Evidence for the evolving role of neoadjuvant and perioperative immunotherapy in resectable non-small cell lung cancer.

The treatment of early-stage non-small cell lung cancer (NSCLC) is becoming increasingly complex. Standard of care management for the past decade has been adjuvant chemotherapy following curative intent resection regardless of nodal status or tumour profile. With the increased incorporation of immunotherapy in NSCLC, especially in the locally advanced, unresectable, or metastatic settings, multiple studies have sought to assess its utility in early-stage disease. While there are suboptimal responses to neoadjuvant chemotherapy alone, there is a strong rationale for the use of neoadjuvant immunotherapy in tumour downstaging, based upon the concept of enhanced T cell priming at the time of a high tumour antigen burden, and demonstrated clinically in other solid tumours, such as melanoma. In the NSCLC cancer setting, currently over 20 combinations of chemoimmunotherapy in the neoadjuvant and perioperative setting have been studied with results variable. Multiple large phase III studies have demonstrated that neoadjuvant chemoimmunotherapy combinations result in significant advances in pathological response, disease free and overall survival which has led to practice change across the world. Currently, combination immunotherapy regimens with novel agents targeting alternate immunomodulatory pathways are now being investigated. Given this, the landscape of treatment in resectable early-stage NSCLC has become increasingly complex. This review outlines the literature of neoadjuvant and perioperative immunotherapy and discusses its potential benefits and complexities and ongoing considerations into future research.