Mediastinal staging and restaging techniques in locally advanced non-small cell lung cancer in the era of neoadjuvant and perioperative chemoimmunotherapy-a narrative review.

Background and Objective: Lung cancer (LC) is the leading cause of cancer-related death in worldwide. Approximately 70% of patients have advanced or locally advanced non-small cell lung cancer (LA-NSCLC) at diagnosis, which confers an unfavorable prognosis. Recently, neoadjuvant and perioperative chemoimmunotherapy has demonstrated survival benefit, becoming the new standard treatment. The most significant prognostic factor in LA-NSCLC is N2 mediastinal nodal involvement. In this scenario, mediastinal staging and restaging techniques play a key role by enabling lymph node evaluation and assessment of response to treatment. Nevertheless, despite current mediastinal staging methods, unsuspected pN2 disease is detected in 25% of patients. Furthermore, evidence regarding mediastinal staging and restaging techniques in the setting of neoadjuvant and/or perioperative chemoimmunotherapy remains limited, highlighting the need to clarify their utility in the era of neoadjuvant and perioperative chemoimmunotherapy. The purpose of this review is to identify the scientific evidence regarding mediastinal staging and restaging techniques in patients with LA NSCLC undergoing neoadjuvant and perioperative chemoimmunotherapy. Methods: We searched PubMed/MEDLINE, and Google Scholar for articles published since 1987. Search terms included "NSCLC", "stage III", "neoadjuvant", "mediastinal lymph node", "staging", "restaging". The selection focused on English-language research and reviews addressing LA-NSCLC mediastinal staging and restaging techniques. Key Content and Findings: The article reviews the role of mediastinal staging and restaging techniques in the neoadjuvant and/or perioperative treatment of LA-NSCLC. The limited accuracy of non-invasive methods supports the use of minimally invasive techniques for mediastinal staging and restaging. Conversely, the potential risks of invasive procedures restrict their use to selected situations. It should be noted that evidence for these techniques in the era of chemoimmunotherapy remains scarce, for mediastinal staging data are mainly derived from the chemotherapy treatment setting, whereas for mediastinal restaging the available evidence comes exclusively from positron emission tomography-computed tomography (PET-CT). Conclusions: N2 mediastinal nodal involvement is the most relevant prognostic factor in LA-NSCLC. Regardless of the available mediastinal staging and restaging techniques, unforeseen pN2 disease is detected in a substantial proportion of cases. There is a lack of utility data on these methods in the chemoimmunotherapy setting. Further research is needed to determine their role in current therapeutic approaches.