A Randomized Trial of Radical Surgery versus Thoracic Radiotherapy After Response to Induction Chemotherapy in Patients with Histo-/Cytologically Proven Irresectable Stage IIIA-N2 NSCLC (EORTC 09841)
Reviewer: S. Jack Wei, MD
University of Pennsylvania School of Medicine
Last Modified: May 17, 2005
Presenter: J. van Meerbeeck
Presenter's Affiliation: EORTC Lung Cancer Group
Type of Session: Scientific
- Stage IIIA non-small cell lung cancer (NSCLC) with stage N2 disease is a heterogeneous group of patients representing 15% of all cases of NSCLC at presentation.
- Variable treatment approaches have been attempted with 5-year overall survival (OS) as shown:
- Surgery: 5%
- Chemotherapy + Radical Radiotherapy (RT): 15%
- Chemotherapy + Resection: 18%
- Concurrent Chemoradiotherapy (CTRT): 20%
- Concurrent CTRT + Resection: 27%
- This trial was conducted to determine if surgical resection after response to induction chemotherapy improves outcomes in patients with IIIA-N2 NSCLC
Materials and Methods
- Patients with stage IIIA-N2 NSCLC were treated with 3 cycles of platinum-based induction chemotherapy (cisplatin (>=80 mg/m2) or carboplatin (AUC>=5) combined with at least one other drug) and then assessed for response.
- Patients with stable or progressive disease were treated off study, while patients with any type of response were randomized to:
- Thoracic RT (60 Gy in 2 Gy/day)
- Surgical Resection with intent of radical resection of tumor and dissection of hilar and mediastinal lymph nodes within 6 weeks of randomization
- Post-operative RT was recommended in cases of incomplete resection (either positive surgical margin or highest sampled mediastinal lymph node positive) with dose of 56 Gy (2 Gy/day) 4-10 weeks after resection.
- Eligible patients had cytologically or histologically proven N2 disease with clinical stage IIIA disease, were considered unresectable by a local surgeon, had measurable disease, and were fit for combined modality therapy.
- Primary endpoint was OS.
- Secondary endpoints included progression-free survival (PFS) and toxicity.
- 579 patients registered with 332 (57%) randomized. The majority of non-randomized patients were non-responders to induction chemotherapy.
- 94% of patients in RT arm received RT, and 92% in surgery arm received surgery.
- Treatment arms were well-balanced for gender, age, histology, stage, and response to induction chemotherapy.
- For the induction chemotherapy, overall response rate (OR) was 62% with 4% complete response (CR), and 58% partial response (PR).
- In the RT arm, 80% received >=60 Gy
- 8% late 3/4 pulmonary toxicity.
- In the surgery arm, 47% underwent pneumonectomy, 38% underwent lobectomy, and 21% underwent thoracotomy only.
- 50% received complete resection
- 4% operative mortality
- 56% have ypN2 disease at time of resection, 42% have ypN0-1 disease.
- Median follow-up: RT 73.1 mo, surgery 67.2 mo.
- Median survival for RT vs. surgery: 17.5 mo vs. 16.4 mo (p=NS)
- 5-year OS: 14.0% vs. 15.7% (p=NS)
- Median PFS: 11.3 mo vs. 9.0 mo (p=NS)
- 2-year PFS: 24.2% vs. 26.5% (p=NS)
- Patients undergoing pneumonectomy and those with pathologic N2 disease after induction chemotherapy had worse outcome.
- Surgical resection after response to chemotherapy does not improve outcomes in stage IIIA-N2 patients compared to RT.
- Surgery is feasible and has acceptable rate of post-operative mortality in this setting.
- Induction chemotherapy results in mediastinal downstaging in 40% of patients with resected disease, a minority of which have CR.
- Mediastinal downstaging at surgery predicts improved outcome if pneumonectomy is avoided.
- Chemoradiotherapy is to remain the standard treatment for future EORTC studies in stage IIIA-N2 NSCLC