Perioperative Therapy in Oncogene-Driven Non-Small Cell Lung Cancer: Current Strategies and Unanswered Questions

Area of Science:

• Oncology
• Precision Medicine
• Thoracic Surgery

Background:

• Perioperative therapy is crucial for resectable non-small cell lung cancer (NSCLC).
• Molecular testing is essential for guiding treatment in early-stage NSCLC, similar to metastatic disease.
• Tissue-based next-generation sequencing is vital due to limited liquid biopsy sensitivity in early-stage NSCLC.

Purpose of the Study:

• To review the current landscape and future directions of perioperative therapy in oncogene-driven NSCLC.
• To highlight the need for optimized molecular testing pathways and tissue utilization.
• To discuss the evolving roles of targeted therapies and immunotherapy in early-stage NSCLC management.

Main Methods:

• Review of current literature and clinical trial data on perioperative targeted therapies and immunotherapy for NSCLC.
• Analysis of the role of molecular testing, including next-generation sequencing and molecular residual disease assessment.
• Discussion of ongoing research investigating specific mutations (EGFR, ALK, KRAS, BRAF) and treatment responses.

Main Results:

• Adjuvant osimertinib is standard for EGFR-mutant NSCLC; ALK inhibitor investigations are ongoing.
• Unanswered questions persist regarding perioperative TKI therapy, molecular residual disease, and high-risk subgroups.
• The efficacy of perioperative chemo-immunotherapy in oncogene-driven NSCLC requires further clarification, though some mutations like KRAS/BRAF may show promise.

Conclusions:

• Optimizing perioperative strategies requires addressing the integration of targeted therapies and immunotherapy in oncogene-driven NSCLC.
• Further research is needed to refine treatment decisions and improve outcomes for patients with resectable NSCLC.
• Defining the role of molecular residual disease assessment and specific TKIs is critical for advancing perioperative care.