Perioperative Management of Non-Small Cell Lung Cancer in the Era of Immunotherapy

Abstract

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related mortality worldwide. Nonetheless, deeper molecular understanding of NSCLC has resulted in novel therapeutic approaches, including targeted therapy and immunotherapy, which have improved patient prognosis and outcomes in recent years. Immune checkpoint inhibitors (ICIs), with or without chemotherapy, are now considered valuable components of treatment for NSCLC cases that do not have specific actionable genetic mutations. Patients with actionable genetic mutations are candidates for targeted therapies. The primary focus of this review is the rationale for using ICIs in the perioperative setting for patients with resectable NSCLC and in advanced disease settings. Furthermore, we compare the benefits of using ICIs with the challenges associated with their clinical implementation in resectable and advanced NSCLC. Finally, we emphasize the development of novel treatment strategies that potentially provide an optimal treatment choice for patients with advanced NSCLC.

Keywords: NSCLC; adjuvant therapy; immunotherapy; neoadjuvant therapy; targeted therapy.

Figure 1

Workflow for rNSCLC. rNSCLC: resectable non-small cell lung cancer; RT: radiotherapy; CRT: chemoradiotherapy; TKI: tyrosine kinase inhibitor; CIT: chemoimmunotherapy.

Figure 2

Schematic of the THIO-101 clinical trial design (79). Primary endpoints: safety, ORR (objective response rate), and DCR (CR, PR, and SD). Secondary endpoints: DoR (duration of response), PFS (progression-free survival), and OS (overall survival). Exploratory endpoints: PK and PD (activity of THIO in CTCs (circulating tumor cells) measured by specific biomarkers). The schematic has been adapted from the ELCC poster, 2025.