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)
Background: The optimal locoregional treatment -TRT or S- following
systemic ICT of pts with stage IIIA-N2 NSCLC is unclear. 5-year survival rate in
uncontrolled series of either modality varies between 5-25%. Methods: selected pts with
histological or cytological proven stage IIIA-N2 NSCLC were given 3 cycles of
platinum-based ICT. Responding pts were then randomized between S: radical resection with
lymph node dissection and optional postoperative radiotherapy (PORT), or TRT: at least 40
Gy in 2 Gy daily fractions on the mediastinum with a boost to at least 60 Gy on the
involved field (IF). In order to observe an increase of 5-year overall survival (OS) from
15 (TRT) to 25% (S), 292 events out of 358 randomized pts had to be observed (log rank
test, power 80%, type I error 5%). Secondary endpoints were progression free survival
(PFS) and toxicity. Results: ICT achieved an average response rate of 61.5% (95% CI
57.6-65.5) among the 572 registered pts who started protocol treatment. Of these, 333 were
randomized (167 to S and 166 to TRT), having the following characteristics: median age 62
years; male 74%; squamous/non-squamous: 39/61%; T1/2/3: 12/72/15%. In the 154 operated
pts, the following rates were observed: exploratory thoracotomy: 14%; radical resection:
51%; pathological downstaging: 42%; operative mortality: 4%; PORT 39%. Among 155 pts
randomized to TRT and actually irradiated, median total treatment time was 43 days
(15-60). CT- scan planning was used in 92%. The median total dose delivered to the normal
mediastinum/IF was 40/60 Gy, respectively. Any kind of grade 3/4 toxicity occurred in 3.9%
of irradiated TRT pts. With a median follow up of 72 months, median, 2 and 5 year OS for
pts randomized to S and TRT are 16.4 vs.17.5 months, 35 vs. 41% and 16 vs. 13%,
respectively (HR 0. 95, 95% CI 0.75-1.19). Median and 2y PFS for pts randomized to S and
TRT are 9.0 vs.11.4 months and 27 vs. 24%, respectively (p= 0.6). Conclusion: In selected
pts with proven stage IIIA-N2 NSCLC and a response to ICT, S improves neither OS nor PFS
as compared to TRT |