Survival is better predicted with a new classification of stage III unresectable non-small cell lung carcinoma treated by chemotherapy and radiotherapy

Abstract

The 1997 International staging system (ISS) classification separated stage III non-small cell lung cancer (NSCLC) into stages IIIA and IIIB. In a previous study including unresectable NSCLC initially treated with chemotherapy, we analysed survival according to tumour (T) and node (N) stages and derived a classification into stages IIIβ (T3-4N3) and IIIα (other TN stage III) that had a better discrimination on survival distribution. The aim of this study was to validate these results in a further set of patients. Patients with unresectable stage III NSCLC included in a phase III trial assessing the role of increased dose chemotherapy (SuperMIP: mitomycin 6 mg/m 2, ifosfamide 4.5 g/m 2, cisplatin 60 mg/m 2, carboplatin 200 mg/m 2) in comparison to standard chemotherapy MIP (mitomycin 6 mg/m 2, ifosfamide 3 g/m 2, cisplatin 50 mg/m 2), before thoracic irradiation (60 Gy in 30 fractions over 6 weeks) were the subject of this study. Survival distributions were assessed by the method of Kaplan–Meier. Survival comparisons were made by the log-rank test. Multivariate analyses using Cox regression models, included all potential prognostic factors for survival with a P-value <0.2 in univariate analysis. According to the 1997 International staging system classification, 328 eligible patients were included in the study. There was no imbalance between the two arms. Five parameters were significantly associated ( P≤0.05) with survival in univariate analysis: European lung cancer working party (ELCWP) staging (IIIα[ n=294 pts] versus IIIβ [ n=46]), Karnofsky index, weight loss, platelet count and haemoglobin level. These variables as well as the 1997 ISS staging, white blood cell (WBC) count, LDH and sodium levels were included in a multivariate analysis. Two models were constructed, including either the ELCWP or the 1997 ISS. In model 1 (ISS included), Karnofsky index (HR 0.69; 95% confidence interval (CI) 0.47–1.00; P=0.05) and haemoglobin (HR 1.49; 95% CI 1.11–1.99; P=0.007) were found significant. In model 2, including ELCWP staging, two variables were associated with survival: ELCWP staging (HR 1.68; 95% CI 1.20–2.35; P=0.002) and haemoglobin (HR 1.54; 95% CI 1.15–2.07; P=0.01). Conclusion: In initially unresectable stage III NSCLC treated by chemotherapy and radiotherapy, we validated the results of our previous study. The classification into stages IIIβ (T3-4N3M0) and IIIα (other TN stage III) better discriminates the patients in term of survival than the 1997 ISS classification.