Indolence versus aggression in non-small cell lung cancer: defining heterogeneity to impact clinical outcomes

While important new findings in the treatment of advanced non-small cell lung cancer (NSCLC) have led to significant progress, it has been incremental. In the past 30 years the five-year survival rate for lung cancer has increased by only 5% (1). Despite the major survival advantage conferred to patients with localized disease, only 17% of NSCLC diagnoses were made at stage I–II as of 2014 (2). For this reason, considerable efforts have historically focused on improving early detection through development of screening programs. Following the publication of the NCI-funded National Lung Screening Trial (NLST), the Centers for Medicare and Medicaid Services (CMS) added annual low-dose computed tomography (LDCT) as a preventive service benefit in 2015. This has led to a rapid expansion of lung cancer screening programs. The NLST demonstrated a 20% relative reduction in cancer-specific mortality with annual LDCT screening in high-risk patients and resulted in a much improved probability of early stage disease at diagnosis (3). Specifically, amongst patients with screen-detected lung cancers, approximately 70% were stage I–II at diagnosis and over 50% were stage IA (3). The observation that screen-detected lung cancer is more likely to be at an early, localized stage is consistent with the findings of other large-scale prospective screening studies. Thus, the implementation of lung cancer screening programs is expected to lead to a stepwise increase in early stage diagnoses.