Current status of induction treatment for N2-Stage III non-small cell lung cancer

Locally advanced non-small cell lung cancer (NSCLC), particularly clinical Stage IIIA NSCLC with mediastinal lymph node metastasis, is known to be quite heterogeneous, comprising approximately one-fourth of cases of NSCLC. In this subset, patients with a minor tumor load in the mediastinal lymph nodes, such as microscopically or pathologically proven N2 in the resected specimens, are treated with surgery followed by adjuvant chemotherapy. Meanwhile, the current standard of care for patients with bulky or infiltrative N2 disease is concurrent chemoradiotherapy. The potential role of surgery in multi-modality treatment for clinical N2-Stage IIIA remains controversial. Several prospective clinical trials of this subset have been conducted; however, the heterogeneity of the N2 status and differences in chemotherapy regimens and/or radiation modalities between clinical trials make the results difficult to compare. No optimal chemotherapy regimen has been established to control possible micrometastasis, and radiotherapy is often used to achieve maximum local disease control and minimize post-surgical complications. This review summarizes the findings of prospective clinical trials that assessed the role of surgery in treating clinical N2-Stage IIIA patients within the last two decades and discusses the present status of induction treatment followed by surgery for clinical N2-Stage IIIA NSCLC.