Preoperative Chemotherapy Followed by Surgery Compared With Primary Surgery in Resectable Stage I (Except T1N0), II, and IIIa Non–Small-Cell Lung Cancer

PURPOSE: To evaluate whether preoperative chemotherapy (PCT) could improve survival in resectable stage I (except T1N0), II, and IIIA non–small-cell lung cancer (NSCLC). PATIENTS AND METHODS: A randomized trial compared PCT to primary surgery (PRS). PCT consisted of two cycles of mitomycin (6 mg/m 2 , day 1), ifosfamide (1.5 g/m 2 , days 1 to 3) and cisplatin (30 mg/m 2 , days 1 to 3), and two additional postoperative cycles for responding patients. In both arms, patients with pT3 or pN2 disease received thoracic radiotherapy. RESULTS: Three hundred fifty-five eligible patients were randomized. Overall response to PCT was 64%. There were two preoperative toxic deaths. Postoperative mortality was 6.7% in the PCT arm and 4.5% in the PRS arm (P = .38). Median survival was 37 months (95% confidence interval [CI], 26.7 to 48.3) for PCT and 26.0 months (95% CI, 19.8 to 33.6) for PRS (P = .15). Survival differences between both arms increased from 3.8% (95% CI, 1.3% to 25.1%) at 1 year to 8.6% (95% CI, 2.64% to 24.4%) at 4 years. A quantitative interaction between N status and treatment was observed, with benefit confined to N0 to N1 disease (relative risk [RR], 0.68; 95% CI, 0.49 to 0.96; P = .027). After a nonsignificant excess of deaths during treatment, the effect of PCT was significantly favorable on survival (RR, 0.74; 95% CI, 0.56 to 0.99; P = .044). Disease-free survival time was significantly longer in the PCT arm (P = .033). CONCLUSION: Although impressive differences in median, 3-year, and 4-year survival were observed, they were not statistically significant, except for stage I and II disease.