Optimal Treatment of Stage IIIA-N2 Non–Small Cell Lung Cancer: A Neverending Story?

Citations of this article
Mendeley users who have this article in their library.


Stage IIIA-N2 NSCLC remains the Achilles' heel in thoracic surgery, with diagnostic and therapeutic strategies being hotly debated at plenary sessions of major oncological conferences. 1 This results from many uncertainties and imprecise definitions surrounding the specific category of NSCLC lying between clearly resectable disease (with complete resection offering the best chance of long-term survival) and unresectable disease (which is treated mainly by concurrent or sequential chemoradiation in patients with good performance status). 2 The brief report " Resectable Clinical N2 Non–Small Cell Lung Cancer; What Is the Optimal Treatment Strategy? An Update by the British Thoracic Society Lung Cancer Specialist Advisory Group, " which is published in the current issue of the Journal of Thoracic Oncology, provides a concise and timely review addressing main questions such as the type of induction therapy; the advantages of trimodality versus bimodality therapy; and the delicate interplay between chemotherapy, radiotherapy, and surgery as treatment modalities. 3 The authors prudently conclude that " when discussing treatment for fit patients with potentially resectable cN2 NSCLC, lung cancer teams should consider trimodality treatment with chemotherapy, radiotherapy, and surgery or bimodality treatment with chemotherapy and either surgery or radiotherapy. " Although randomized controlled trials performed in patients with stage IIIA-N2 NSCLC and evaluating a large number of patients are available, the conclusions of these studies cannot be considered definitive, as most of them were designed in a previous century, before the era of routine positron emission tomographic scanning and before the advent of minimally invasive staging and surgical techniques. Equally, new and more effective radiotherapy protocols and devices limiting radiation to exposure to surrounding critical organs such as the heart and spinal cord have been introduced. Moreover, patient populations were quite heterogeneous and N2 disease was not always pathologically proven. Three phase III trials need to be specifically mentioned: Intergroup (INT) 0139, European Organisa-tion for Research and Treatment of Cancer (EORTC) 08941, and the more recent ESPATUE trial. 4–6 Both the INT 0139 and the EORTC trials were randomized phase III studies including histologically proven stage IIIA-N2 NSCLC. 4,5 Induction therapy consisted of chemoradiation in the INT study and chemotherapy in the EORTC trial. Subsequently, patients were randomized to an operation or further chemoradiotherapy in the U.S. trial and to an operation or radiotherapy in the EORTC trial. Quite remarkably, the results of the INT trial were published in an European journal, and the results of the European trial in an American journal. In both trials there was no difference in overall survival, but in the INT study progression-free survival was significantly better in the surgical arm. In a much-debated exploratory subanalysis, patients undergoing lobectomy had a better outcome than did a matched population treated by radiotherapy. The more recent ESPATUE trial had a rather complicated design: patients with clinical stage IIIA and selected patients with stage IIIB NSCLC were treated with induction chemotherapy followed by chemo-radiation and were subsequently randomized to an operation or a concurrent chemoradiotherapy boost.




Van Schil, P. E. (2017, September 1). Optimal Treatment of Stage IIIA-N2 Non–Small Cell Lung Cancer: A Neverending Story? Journal of Thoracic Oncology. Elsevier Inc. https://doi.org/10.1016/j.jtho.2017.07.001

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free