Distinct Therapeutic Strategies in Resectable vs. Metastatic NSCLC

Welcome back to another AJMC Peer Exchange series. In this episode titled, Distinct Therapeutic Strategies in Resectable vs. Metastatic NSCLC, Dr. Martin Dietrich led the conversation about the following question:

In general, how does your treatment approach differ with resectable vs. metastatic NSCLC?

Dr. Jared Weiss highlighted Treatment approaches for non–small cell lung cancer (NSCLC), which differ substantially based on resectability, as goals shift from curative intent in early-stage disease to disease control and survival prolongation in the metastatic setting. In resectable NSCLC, surgery remains the cornerstone of therapy, often combined with neoadjuvant or adjuvant chemotherapy, immunotherapy, and/or targeted therapy depending on tumor stage and biomarker status. The integration of perioperative immunotherapy has improved pathologic response rates and event-free survival, emphasizing a multimodal strategy aimed at eradicating micrometastatic disease. Molecular testing is increasingly important even in early-stage disease to guide adjuvant targeted therapies for patients with actionable alterations. In contrast, metastatic NSCLC is managed with systemic therapy as the primary modality, including immunotherapy, targeted therapy for oncogenic drivers, and chemotherapy, with treatment selection driven largely by PD-L1 expression and comprehensive genomic profiling. Local therapies such as radiation or surgery play a limited, palliative, or consolidative role in oligometastatic cases rather than serving as definitive treatment. Sequencing of therapies, management of resistance mechanisms, and maintenance strategies are critical considerations in advanced disease. Overall, resectable NSCLC prioritizes cure through multimodality treatment, whereas metastatic NSCLC focuses on personalized systemic therapy to maximize survival and quality of life..

Throughout the conversation, the experts provide a comprehensive reflection on the field and the factors that may shape how clinicians approach care moving forward.

In the next episode, Evolving Role of PD-L1 and Neoadjuvant Immunotherapy in Resectable NSCLC, panelists will continue their discussion on NSCLC and highlight a key immunotherapy clinical trial.