Abstract and Introduction
Abstract
In early stage non-small cell lung cancer (NSCLC) large randomized trials have demonstrated that in patients with radically resected disease adjuvant chemotherapy improves 5-year survival rates. However, a customization of systemic treatment is needed to avoid treatments in patients cured by surgery alone or to justify the use of adjuvant chemotherapy in high risk patients, including those in stage IA. Recently, the possibility of identifying prognostic and predictive factors related to the genetic signatures of the tumor that could affect adjuvant and neo-adjuvant treatment choices for resectable non-small cell lung cancer (NSCLC) has been of interest. This review summarizes the current status and future opportunities for clinical application of genotyping and genomic tests in early NSCLC.
Introduction
Surgery remains the only potentially curative treatment for early-stage non-small cell lung cancer patients (NSCLC) resulting in 5-year survival rates ranging from 77% in pathological stage IA to 23% in stage IIIA tumors.
Clinical trials and meta-analyses have demonstrated that in patients with early-stage NSCLC adjuvant chemotherapy improves survival with an average benefit of 5% at 5 years and, consequently, adjuvant chemotherapy is recommended for patients with resected stage II-III NSCLC. Nevertheless, a proportion of stage I patients have poor prognosis and may benefit significantly from adjuvant chemotherapy, while some relatively good prognosis stage II patients may not share similar benefits. Therefore, new diagnostic paradigms are urgently needed to select stage I-II subjects who may take advantage from adjuvant chemotherapy and clinical trials.
The strongest clinical prognostic factors in NSCLC include stage, sex, age, and performance status, but a better individualization of treatment approaches requires a more precise understanding of the molecular features of lung cancer.
A wide array of individual molecular markers have been tested in advanced as well as early stage NSCLC for prognostic and predictive value and this review will focus on the current existing evidence to support their investigational value. Most of these molecular markers have been found to be either prognostic and/or predictive at the same time. One of the first and largest retrospective biomarker studies in 515 resected stage I NSCLC patients failed to show any significant association between survival and the expression of an extensive panel of biomarkers, including epidermal growth factor receptor (EGFR), HER2/neu, bcl-2, p53 and angiogenesis markers.
Lastly, the human genome project, allowed the development and clinical applications of genomic-based assays, including increasingly dense microarray platforms for global analyses of gene expression, copy number variation, DNA methylation and microRNA and several genomic signatures have been identified and tested in early stage NSCLC for their prognostic value.