History and Future of Multimodality Treatment for N2 NSCLC

Abstract

Among non-small cell lung cancer (NSCLC) patients, those with mediastinal lymph node metastasis are categorized as N2 NSCLC. Before the advent of radiotherapy and chemotherapy, surgical resection including mediastinal lymph node metastasis was actively carried out for N2 NSCLC. In the era of definitive radiotherapy, sequential chemoradiotherapy and concurrent chemoradiotherapy, it has become possible to obtain a cure without surgery. However, the results of chemoradiotherapy have been stagnant, at a 5-year survival rate of 15% to 20%. For years, clinical trials have explored stronger local therapies and systemic treatments. For example, high-dose chemoradiotherapy, the addition of cetuximab (EGFR antibody) or tecemotide (MUC1 peptide vaccine) and the development of novel chemotherapeutic drugs (e.g. pemetrexed, S-1) have been examined for application in treating N2 NSCLC. In addition to improving the treatment outcomes, attempts to decipher the heterogeneity of N2 NSCLC and deliver appropriate local therapy according to the anatomical position of the primary tumor and mediastinal lymph node metastasis have also been under development. In this article, I will provide an overview of the development of treatment strategies for patients with N2 NSCLC.