Prognostic markers in resectable non-small cell lung cancer: a multivariate analysis

Objective: To identify the prognostic significance of certain clinical, cel lular and immunologic markers in resectable non-small cell lung cancer (NSC LC). Design: A cohort of patients with resectable NSCLC was prospectively f ollowed up for 8 years (100% follow-up). Setting: A university hospital in a large Canadian city. Patients: One hundred and thirteen consecutive patie nts who underwent surgical resection of primary NSCLC. Main outcome measure s: Presence of peritumoral B lymphocytes (identified with antibody to CD20) and T lymphocytes (antibody to CD43), along with tumour markers (carcinoem bryonic antigen [CEA], keratin, cytokeratin, S-100 protein, vimentin, chrom ogranin) and other factors such as age, sex, cell type, American Joint Comm ittee on Cancer (AJCC) stage, histologic grade, DNA ploidy and S-phase frac tion were correlated with survival. Results: The mean age of patients in th e study was 66.0 years; 60% were male. Histologic types of the tumours were : adenocarcinoma 57 (50.4%), squamous cell 47 (41.6%), adenosquamous 6 (5.3 %) and large cell 3 (2.6%). ATCC stages were: I 66 (58.4%), II 20 (17.7%) a nd III 27 (23.9%). Histologic grades were: I(well differentiated) 31 (27.4% ), II 50 (44.2%), III 29 (25.7%) and IV 3 (2.6%). Survival was 85% at 1 yea r (95% confidence interval [CI] 76%-90%), 44% at 5 years (95% CI 34%-53%) a nd 34% at 10 years (95% CT 22%-46%). Multivariate analyses using the Cox pr oportional hazards model for survival confirmed ATCC stage (p < 0.001) in a ll histologic subtypes to be the strongest factor of independent prognostic significance. It also revealed the presence of CD20-stained B lymphocytes (p = 0.04) in the peritumoral region of all rumours to be a positive progno stic factor. This relation was especially strong For nonsquamous cell carci nomas (p < 0.001). For squamous cell carcinomas, the immunohistochemical pr esence of CEA was of marginally negative prognostic value (P = 0.04). DNA p loidy and a high S-phase fraction showed no evidence of prognostic value fo r stags I rumours, but for stages II and III rumours there was strong evide nce of prognostic value (p < 0.001 jointly). The evidence for DNA ploidy wa s especially strong in stages II and III squamous cell tumours (p = 0.008), and for a high S-phase fraction nas strongest in stages II and III nonsqua mous cell tumours (p = 0.002). Conclusions: ATCC stage remains the most imp ortant prognostic indicator fi-om a variety of clinical variables and tumou r markers in postoperative patients with resectable NSCLC. For nonsquamous cell lung carcinomas, the presence of peritumoral B lymphocytes was strongl y associated with improved survival, suggesting an important role for humor al mediated immunity.