Debate: why surgery should remain central in the management of locally advanced (Stage III) non-small-cell lung cancer.

Abstract

Stage III non-small cell lung cancer (NSCLC) comprises a broadly heterogeneous disease with historically poor survival, and treatment decisions must account for both pathophysiology and resectability. Despite conclusions from older trials that questioned the role of surgery, modern evidence supports surgical resection as an indispensable component of treatment when performed by experienced thoracic surgeons. Advances in neoadjuvant systemic therapy, particularly chemo-immunotherapy, have significantly improved outcomes and reinforced the added value of surgery in appropriately selected Stage III NSCLC patients. In PACIFIC, consolidation durvalumab after concurrent chemoradiation improved progression-free (16.9 vs 5.6 months) and overall survival (47.5 vs 29.1 months). Also, perioperative pembrolizumab reduced progression or death by 42% (*P* < 0.0001) and improved pCR and major pathologic response. Additional trials (NEOTORCH, NADIM 2) showed large reductions in events and higher pCR rates with checkpoint inhibitors plus chemotherapy. Collectively, these data underscore that Stage III NSCLC requires both systemic therapy and durable local control, and neoadjuvant chemo-immunotherapy followed by surgery can significantly improve oncologic outcomes without increasing perioperative mortality in carefully selected patients.