Tumor Markers and the Early Detection of Lung Cancer
Presenter: James Mulshine, MD
Affiliation: National Cancer Institute
Lung cancer has recently outstripped coronary artery disease as the leading cause of smoking related death in the USA. One half of new lung cancers are diagnosed in former smokers. This indicates that smoking cessation alone is insufficient in reducing cancer related mortality. As the lethality of lung cancer is likely related to its frequent diagnosis at an advanced stage, screening efforts may lead to early diagnosis and improved outcomes.
The lung epithelial biomarker heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNP) is being investigated at the NCI for screening purposes. This protein appears to be specific for dysplastic lung epithelial cells. In high risk populations, immunohistochemistry of sputum specimens has been shown to have a sensitivity of 65-95% and specificity of 65-88% for lung cancer. The applicability of this approach to a large moderate risk population remains unclear. A serum based assay may make the test easier to apply to the population as a whole.
Serum or sputum based proteome analysis for potential early lung cancer detection molecules (yet to be characterized) is evolving using mass spectrometry or surface enhanced laser desorption and ionization. These methods are still developing. Sensitivity and specificity in the clinical setting have yet to be established.
High resolution spiral CT likely holds the most promise for effective screening in the immediate future. In the Mayo clinic screening trial of several thousand patients, 75% of lung cancers diagnosed were AJCC stage I, with only 2% stage IV. Similar detection rates have been seen in multiple other smaller trials in high risk populations. The NCI sponsored National Lung Screening Trial will soon reach its accrual goal of 50,000 patients and will shed important light on utility of spiral CT in the larger population. Recent cost-effectiveness data from the New York ELCAP trial postulated a cost of $2,500 per year of life saved by a nationwide CT screening program.
In summary, muliple emerging modalities are in development that hopefully will make population based lung cancer screening a reality, in turn reducing the huge public health burden caused by lung cancer.