Integrated Therapeutic Approaches in the Treatment of Locally Advanced Non-small Cell Lung Cancer

Treatment of locally advanced non-small cell lung cancer (NSCLC) remains a significant challenge for oncologists, despite progress made in recent years in early diagnosis and therapy. This review focuses on integrated therapeutic approaches of patients with locally advanced NSCLC, summarizing the available evidence for patients with potentially resectable disease (stage IIIA-0/3) and with unresectable disease (stage IIIA-4/IIIB) and discussing several key questions related to the use of integrated approaches in NSCLC. Based on current evidence, neoadjuvant platinum-based combination chemotherapy is a treatment option in patients with potentially resectable stage IIIA-0/3: a 2-drug combination of platinum combined with a third-generation drug seems preferable, and at least 3 cycles of chemotherapy should be administered. There are no definitive evidences of clear superiority of surgery compared to radiotherapy for patients obtaining a response with neoadjuvant treatment: however, surgery is associated with a better local control, and subgroup analyses of randomized trials suggest improved outcome in patients in whom a complete resection could be obtained with a lobectomy, avoiding the increased surgical mortality associated with pneumonectomy. Standard treatment for patients with locally advanced, unresectable NSCLC is currently represented by combination of chemotherapy and radiotherapy. Concomitant approach has been proven superior to the sequential administration, although it is associated with higher risk of toxicity. All patients should be evaluated by a multidisciplinary team, skilled in multimodality treatment and should be counselled about risks and potential benefits of the different therapeutic approaches.