MOLECULAR PATHOLOGICAL SUBSTAGING IN 244 STAGE-I NON-SMALL-CELL LUNG-CANCER PATIENTS - CLINICAL IMPLICATIONS

Purpose: To retrospectively construct a comprehensive multivariate mod el of cancer recurrence and to design a molecular pathologic substagin g system in stage I non-small-cell lung cancer (NSCLC). Methods: All p atients with stage I NSCLC resected at Brigham and Women's Hospital (B oston, MA) between 1984 and 1992 with adequate clinical follow-vp were studied. The importance of three demographic characteristics, surgica l extent, 11 pathologic features, and seven molecular factors on cance r-free survival was examined. Results: Two hundred forty-four patients were studied, with 25 noncancer deaths and 80 patients with recurrent disease. Significant univariate predictors (P < .05) of cancer recurr ence were age older than 60 years, male sex, wedge resection, World He alth Organization (WHO) adenocarcinoma subtype solid tumor with mucin, lymphatic invasion, and p53 expression. Multivariate analysis identif ied nine independent predictors of recurrence: solid tumor with mucin, a wedge resection,;tumor diameter of 4 cm or greater, lymphatic invas ion, age older than 60 years, male sex, p53 expression, K-ras codon 12 mutation, and absence of H-ras p21 expression. Multivariate cancer-fr ee survival (CFS) analysis in the 180 patients who underwent lobectomy or pneumonectomy led to the elimination of sex and age, which left si x independent factors. Conclusion: Lobectomy or pneumonectomy should b e performed in stage I NSCLC. Using the six independent factors for re current disease, we propose a pathologic molecular substaging system. Patients with two factors or less are graded la, with a 5-year CFS rat e of 87%; those with three factors are graded Ib, with a 5-year CFS ra te of 58%; and those with four factors or more are graded Ic, with a 5 -year CFS rate of 21%. (C) 1998 by American Society of Clinical Oncolo gy.