Table 1

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

StudyNotesStudy armsRecruitmentPrimary endpointResults
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
60–62.5 Gy in 30–32 fractions.
Target 358 patients
332 randomised
5-year OS15.7% 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
complete radiotherapy to 61 Gy.
Target 612 patients
429 recruited
5-year OS27% vs 20%
HR 0.87 (0.7–1.1), p=0.24
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
chemoradiotherapy boost.
Target 300 patients
246 recruited
161 randomised following induction.
5-year OS44% 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
3 cycles of induction chemotherapy plus 44 Gy radiotherapy.
All patients for surgical resection after induction treatment.
Target 240 patients
232 recruited
Stopped at third analysis.
EFS11.6 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.