Pre- or Perioperative Immunotherapy Combined with Chemotherapy Versus Chemotherapy Alone in Resectable Non-Small Cell Lung Cancer (NSCLC): A Systematic Literature Review

Background/Objectives: Immunotherapy has emerged as an important field of research in non-small-cell lung cancer (NSCLC) and has demonstrated promising results in clinical practice. In recent years, multiple studies have been conducted, increasing the amount of available data. Therefore, the aim of this systematic review is to assess the combination of perioperative immunotherapy with chemotherapy compared to chemotherapy only in patients with resectable NSCLC in terms of survival, pathological response, and adverse events. Methods: The clinical databases PubMed, Cochrane Library, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) were systematically searched, up to March 2026. A two-step selection process served as the screening for eligibility, in which the assessment was based on pre-defined inclusion and exclusion criteria. This process was visualized via a PRISMA diagram. For each included study, the risk of bias was assessed with the help of the Cochrane Risk of Bias 2.0 tool and the Newcastle Ottawa Scale. A narrative synthesis was performed due to heterogeneity. Data were extracted into tables. Results: A total of 16 studies, involving 4646 patients in total, met the eligibility criteria, and their data on study population, intervention, comparison, and outcome were extracted into tabular form. Survival and pathological response rates are continuously higher in patients treated with immunochemotherapy. Findings on adverse events differed across the individual studies, though the results indicate an increased risk of treatment-related adverse events (TRAEs) in patients undergoing the combined treatment approach. Discussion/Conclusions: Chemoimmunotherapy leads to superior clinical outcomes in terms of survival and pathological response rates, though the trend towards a higher incidence and severity of TRAEs warrants further research. The interpretation of findings is limited by differences in study characteristics, mechanism of conduct, and endpoints between the individual studies.