MOLECULAR AND PATHOLOGICAL MARKERS IN STAGE-I NON-SMALL-CELL CARCINOMA OF THE LUNG

Purpose: Although standard treatment of stage I non-small-cell lung ca ncer (NSCLC) consists of surgical resection alone, approximately 50% o f clinical stage I and 30% to 40% of pathologic stage I patients have disease recurrence and die following curative resection. A large numbe r of traditional pathologic and newer molecular markers have been iden tified, which appear to have important prognostic significance in this population. This review attempts to summarize these data comprehensiv ely. Methods: Criteria for study selection were English-language repor ts, identified using Medline and Cancerline, through the fall of 1994. Abstracts from the American Society of Clinical Oncology (ASCO) and t he International Association for the Study of Lung Cancer (IASLG) were also reviewed. Results: Molecular markers are classified as molecular genetic markers, differentiation markers, proliferation markers, and markers of metastatic propensity. A number of these markers have been reported to be highly predictive of outcome in stage I NSCLC, and seve ral reports conclude that a specific biomarker may be, aside from clin ical stage, the most powerful determinant of prognosis in NSCLC. Howev er, little has been done to clarify the relationships between these ne wer biologic markers, classic clinicopathologic variables, and clinica l outcome. Conclusion: At present, a firm conclusion regarding which b iomarkers are most important in predicting outcome is not possible, an d a model that reliably integrates all independent prognostic variable s cannot be developed. A prospective trial is mandatory to address thi s issue, and a study design is suggested that would facilitate the dev elopment of a prognostic index, while simultaneously asking a therapeu tic question. The development of a prognostic index would facilitate f uture trials in which only high-risk stage I patients could be targete d for investigation of postresection adjuvant treatment strategies. (C ) 1995 by American Society of Clinical Oncology.