Optimizing the Care of Patients With Locally Advanced NSCLC With Multimodality Therapy

Unresectable, locally advanced nonsmall cell lung cancer (LA‑NSCLC) accounts for ∼20% to 30% of newly diagnosed cases of NSCLC and remains associated with poor long‑term outcomes. Concurrent chemoradiotherapy (cCRT) has long been the therapeutic backbone for unresectable stage III disease, and the addition of consolidative durvalumab represents a major advance, significantly improving progression‑free and overall survival. Nonetheless, early progression and treatment‑related toxicity limit benefit for many patients, prompting investigation into alternative immunotherapy sequencing and escalation strategies. To date, randomized trials evaluating concurrent immune checkpoint blockade or intensified consolidation have not demonstrated additional survival benefit. In contrast, emerging precision‑medicine approaches-including consolidative targeted therapy for oncogene‑driven tumors-have yielded profound improvements in selected populations. Concurrently, advances in radiation delivery emphasize individualized strategies to optimize local control while minimizing toxicity. This review summarizes evolving systemic and radiation‑based approaches for LA‑NSCLC, highlighting current limitations and future directions to improve outcomes.