Updates and controversies in the rapidly evolving field of lung cancer screening, early detection, and chemoprevention

Abstract

Lung cancer remains the leading cause of cancer-related death in the United States. Cigarette smoking is a well-recognized risk factor for lung cancer, and a sustained elevation of lung cancer risk persists even after smoking cessation. Despite identifiable risk factors, there has been minimal improvement in mortality for patients with lung cancer primarily stemming from diagnosis at a late stage when there are few effective therapeutic options. Early detection of lung cancer and effective screening of high-risk individuals may help improve lung cancer mortality. While low dose computerized tomography (LDCT) screening of high risk smokers has been shown to reduce lung cancer mortality, the high rates of false positives and potential for over-diagnosis have raised questions on how to best implement lung cancer screening. The rapidly evolving field of lung cancer screening and early-detection biomarkers may ultimately improve the ability to diagnose lung cancer in its early stages, identify smokers at highest-risk for this disease, and target chemoprevention strategies. This review aims to provide an overview of the opportunities and challenges related to lung cancer screening, the field of biomarker development for early lung cancer detection, and the future of lung cancer chemoprevention.

Figure 1

Lung cancer screening, early detection, and chemoprevention. While cigarette smoking is the major risk for lung cancer, other risk factors such as toxic exposure including asbestos and a family history of lung cancer influence lung cancer risk. In some individuals susceptible to lung cancer, molecular abnormalities or pre-cancerous dysplastic lesions develop. A subset of these individuals will ultimately progress to lung cancer. Because survival from lung cancer is lower when the disease is diagnosed at an advanced stage, screening high-risk individuals or developing early detection strategies will improve mortality. Although clinical trials have not demonstrated a benefit to chemoprevention, the potential to develop targeted risk-assessment and preventive strategies at all stages of clinical and pre-clinical risk exist. Smoking cessation should be an integral part of all stages of lung cancer screening and treatment.