Treatment of resectable stage IIIA non-small cell lung cancer

Abstract

Surgical treatment of stage IIIA non-small cell lung cancer (NSCLC) remains a controversial area in the management of lung cancer despite being considered as part of combined modality therapy over the last two decades (1). The heterogeneity of stage III disease and the need for a multidisciplinary approach adds complexity to the treatment of resectable stage III NSCLC. Prospective randomized trials including surgery have consistently faced problems in recruiting. Multicenter trials in different countries: the United Kingdom (2), USA (3), France (4) or Japan (5) were terminated early as a result of poor accrual. This may in part be due to the low frequency of suitable patients for surgical treatment. Two modern randomized studies have been published comparing concurrent chemoradiotherapy (CRT) treatments with and without surgery. In the Intergroup 0139 trial (6), patients with stage III N2 disease were treated with concurrent induction chemotherapy plus radiotherapy. If no progression occurred, patients in the surgical group underwent resection and those in the chemoradiation group continued radiotherapy. A total of 396 eligible patients were randomized and there were no differences in overall survival (OS) between the two groups. However, in an exploratory analysis, survival was improved for the patients who underwent lobectomy, but not pneumonectomy, compared with definitive concurrent chemoradiation. In the ESPATUE trial (7) patients with resectable stage IIIA N2 and selected stage IIIB NSCLC were randomized to surgery or definitive concurrent CRT boost after induction chemotherapy followed by concurrent CRT. A total of 245 eligible patients were recruited to induction therapy over a 10-year period, 161 of them were finally randomized to surgery or tailored dose-scaled CRT. It should be pointed out that 63% of those patients were stage IIIB. There was no difference in OS between the arms. Although both trials were planned to demonstrate superiority in the surgery arm, they failed to show any benefit from surgery in terms of OS. Consequently, definitive concurrent CRT is the only strategy which can be given category 1 recommendation for most stage III NSCLC patients.