Randomized controlled trial of resection versus radiotherapy after induction chemotherapy in stage IIIA-N2 non-small-cell lung cancer.
BACKGROUND
Induction chemotherapy before surgical resection increases survival compared with surgical resection alone in patients with stage IIIA-N2 non-small-cell lung cancer (NSCLC). We hypothesized that, following a response to induction chemotherapy, surgical resection would be superior to thoracic radiotherapy as locoregional therapy.


METHODS
Selected patients with histologic or cytologic proven stage IIIA-N2 NSCLC were given three cycles of platinum-based induction chemotherapy. Responding patients were subsequently randomly assigned to surgical resection or radiotherapy. Survival curves were estimated using Kaplan-Meier analyses from time of randomization.


RESULTS
Induction chemotherapy resulted in a response rate of 61% (95% confidence interval [CI] = 57% to 65%) among the 579 eligible patients. A total of 167 patients were allocated to resection and 165 to radiotherapy. Of the 154 (92%) patients who underwent surgery, 14% had an exploratory thoracotomy, 50% a radical resection, 42% a pathologic downstaging, and 5% a pathologic complete response; 4% died after surgery. Postoperative radiotherapy was administered to 62 (40%) of patients in the surgery arm. Among the 154 (93%) irradiated patients, overall compliance to the radiotherapy prescription was 55%, and grade 3/4 acute and late esophageal and pulmonary toxic effects occurred in 4% and 7%; one patient died of radiation pneumonitis. Median and 5-year overall survival for patients randomly assigned to resection versus radiotherapy were 16.4 versus 17.5 months and 15.7% versus 14%, respectively (hazard ratio = 1.06, 95% CI = 0.84 to 1.35). Rates of progression-free survival were also similar in both groups.


CONCLUSIONS
In selected patients with pathologically proven stage IIIA-N2 NSCLC and a response to induction chemotherapy, surgical resection did not improve overall or progression-free survival compared with radiotherapy. In view of its low morbidity and mortality, radiotherapy should be considered the preferred locoregional treatment for these patients.
van Meerbeeck
Jan P
JP
Department of Respiratory Medicine, 7K12IE, University Hospital Ghent, De Pintelaan 185, 9000 Gent, Belgium. jan.vanmeerbeeck@ugent.be
Kramer
Gijs W P M
GW
Van Schil
Paul E Y
PE
Legrand
Catherine
C
Smit
Egbert F
EF
Schramel
Franz
F
Tjan-Heijnen
Vivianne C
VC
Biesma
Bonne
B
Debruyne
Channa
C
van Zandwijk
Nico
N
Splinter
Ted A W
TA
Giaccone
Giuseppe
G
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery*; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D011013:Pneumonectomy; D011446:Prospective Studies; D018714:Radiotherapy, Adjuvant; D012074:Remission Induction / Q000379:methods; D016896:Treatment Outcome
D009944:Organoplatinum Compounds