Table 1

Summary of key randomised controlled trials comparing different treatment strategies in potentially resectable N2 NSCLC

Study	Notes	Study arms	Recruitment	Primary endpoint	Results
Induction chemotherapy followed by surgery versus induction chemotherapy followed by radiotherapy
EORTC 08941 van Meerbeeck et al 5	Recruitment pre-PET and EBUS era. High-volume mediastinal disease and considered unresectable at the outset. Chemoradiotherapy given sequentially and not standard of concurrent.	Three cycles of induction chemotherapy: if response, randomise: surgical resection versus 60–62.5 Gy in 30–32 fractions.	1994–2002 Target 358 patients 332 randomised	5-year OS	15.7% vs 14% HR 1.06 (0.84–1.35), p=0.596
Induction chemoradiotherapy followed by surgical resection versus definitive chemoradiotherapy
Intergroup 0139 Albain et al 6	Recruitment pre-PET and EBUS era. Low-volume mediastinal disease, 74% single-station N2. Statistically significant improvement in PFS (12.8 months vs 10.5 months, p=0.017) with surgical arm. 26% mortality rate for pneumonectomy. Post hoc analysis demonstrating improved survival in matched lobectomy group (33.6 months vs 21.7 months, p=0.002).	Two cycles of induction chemotherapy. Induction radiotherapy 45 Gy. If stable disease, randomise: surgical resection versus complete radiotherapy to 61 Gy.	1994–2001 Target 612 patients 429 recruited	5-year OS	27% vs 20% HR 0.87 (0.7–1.1), p=0.24
ESPATUE Trial Eberhardt et al 11	Highly heterogeneous study population. 32% T4N1. 37% IIIB based on T4N2 staging or N3 disease confined to the contralateral mediastinum.	Three cycles of induction chemotherapy. Induction chemoradiotherapy (45 Gy+one cycle chemotherapy). If remains resectable, randomise: surgical resection versus chemoradiotherapy boost.	2004–2013 Target 300 patients 246 recruited 161 randomised following induction.	5-year OS	44% vs 40%, p=0.34 Overall survival at 5 years for all 246 recruited patients was 34.1%.
Induction chemoradiotherapy followed by surgery versus induction chemotherapy followed by surgery
SAKK Trial Pless et al 10	Low-volume N2 disease with less than 10% of patients having a total mediastinal bulk of disease >5 cm.	Three cycles of induction chemotherapy versus 3 cycles of induction chemotherapy plus 44 Gy radiotherapy. All patients for surgical resection after induction treatment.	2001–2012 Target 240 patients 232 recruited Stopped at third analysis.	EFS	11.6 vs 12.8 months HR 1.1 (0.8–1.4), p=0.67 No significant difference in OS.

EBUS, endobronchial ultrasound; EFS, event-free survival; NSCLC, non-small cell lung cancer; OS, overall survival; PET, positron emission tomography; PFS, progression-free survival.