A randomized trial of radical surgery (S) versus thoracic radiotherapy (TRT) in patients (pts) with stage IIIA-N2 non-small cell lung cancer (NSCLC) after response to induction chemotherapy (ICT) (EORTC 08941)

Reviewer: James M. Metz, MD
Abramson Cancer Center of the University of Pennsylvania
Last Modified: July 5, 2005

Presenter: J. van Meerbeeck
Presenter's Affiliation: University Hospital, Ghent, Belgium
Type of Session: Plenary

Background

There remains significant controversy in the optimal treatment of patients with locally advanced stage IIIA NSCLC with ipsilateral mediastinal lymph node involvement (N2). Chemotherapy has shown significant response rates in this disease. Radiation therapy, when combined with chemotherapy can improve on the outcomes. It remains controversial if patients benefit from surgical resection after induction therapy in patients with N2 disease. This trial, which was also reported at ASCO 2005, was designed to compare surgical resection to radiation therapy after induction chemotherapy in responding patients.

Materials and Methods

579 patients with histologically or cytologically proven IIIA-N2 NSCLC were registered to the trial
All patients received chemotherapy consisting of 3 cycles of either cisplatin (> 80 mg/m2) or carboplatin (AUC > 5)
Responding patients (333) were then randomized to S- radical resection with lymph node dissection and optional postoperative radiation therapy (PORT) to 56 Gy versus TRT- at least 40 Gy to the mediastinum and involved field plus a boost to at least 60 Gy to the involved field.

Results

Overall response rate to chemotherapy was 62% with a CR of 4%
Of the 333 responders who were randomized, 308 were eligible for analysis with 154 in each arm
Median age was 61 years, 74% were male, 61% were non-squamous cell histology
Median interval between last cycle of chemotherapy and surgery or radiation therapy was 51 days (range 17-113)
5 year OS was 17.5% (TRT) vs 16.4% (S) with p=ns
DFS was 11.3 months (TRT) vs 9.9 (S) months with p=ns
Of the S patients, 50% had an R0 resection, there was a 4% operative mortality, and 27% had PORT.
Patients who had a pnuemonectomy did significantly worse at 5 years OS

Author's Conclusions

Induction chemotherapy has a significant response rate but few CR's
Surgical resection does not improve outcome in IIIA NSCLC
Chemotherapy and radiation therapy are to remain the standard treatment arm for future EORTC trials

Clinical/Scientific Implications

This is an important study that contributes significantly to our knowledge in the treatment of IIIA NSCLC. The results of this study mirror those of the recently reported US Intergroup study. In the Intergroup study patients initially received induction treatment with cisplatin/etoposide/TRT and were then randomized to either surgical resection or completion of definitive radiation therapy. After 81 months of follow-up there was no benefit to the addition of surgery. However, patients who received a pnuemonectomy did significantly worse while those that had a lobectomy did better. In the current EORTC study, there was no benefit found for the addition of surgery over radiation therapy. The EORTC has decided to make chemotherapy and radiation therapy the standard arm for future trials of N2 disease. Taken together, these two studies help further refine the treatment of IIIA NSCLC. At the current time, patients with macroscopic N2 disease or disease requiring a pneumonectomy should be offered definitive chemotherapy and radiation therapy without surgery. Selected patients with minimal or microscopic N2 disease that would need a lobectomy may be considered for surgical resection after induction therapy.