Biomarkers for Lung Cancer Screening and Detection

Abstract

Lung cancer is the leading worldwide cause of cancer mortality, as it is often detected at an advanced stage. Since 2011, low-dose CT scan-based screening has promised a 20% reduction in lung cancer mortality. However, effectiveness of screening has been limited by eligibility only for a high-risk population of heavy smokers and a large number of false positives generated by CT. Biomarkers have tremendous potential to improve early detection of lung cancer by refining lung cancer risk, stratifying positive CT scans, and categorizing intermediate-risk pulmonary nodules. Three biomarker tests (Early CDT-Lung, Nodify XL2, Percepta) have undergone extensive validation and are available to the clinician. The authors discuss these tests, with their clinical applicability and limitations, current ongoing evaluation, and future directions for biomarkers in lung cancer screening and detection.See all articles in this CEBP Focus section, "NCI Early Detection Research Network: Making Cancer Detection Possible."

Figure 1:

Like an iceberg, the bulk of cases of lung cancer are not only not detected by screening, but occur in patients not eligible for screening. Approximately 4% of NLST-eligible patients undergo screening. If all NLST-eligible patients underwent screening, only 27% of lung cancers would be detected, similar to the portion of an iceberg seen above water. The remaining 73% of lung cancers occur in those ineligible for screening, for instance those with only a light smoking history, those who have quit > 15 years ago, or those who have never smoked. Biomarkers in high-risk individuals can decrease the rate of false positives after CT-based screening. In lower-risk individuals, biomarkers can be used to identify patients at higher risk who may benefit from screening.