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Lung cancer is the number one cause of cancer death in the U.S. The vast majority of lung cancers are linked to smoking and it represents one of the most important tobacco-related diseases. The reason lung cancer is so lethal is that in the majority of patients it is diagnosed after it has spread from its starting point in the lung to distant sites such as the brain, liver, or bone. Unfortunately, once lung cancer has spread it is considered incurable. However, patients who are diagnosed with “early stage” lung cancer that is confined to a single area in the lung can often be cured by removal or destruction of the tumor. Recently, a large clinical trial showed that early detection of lung cancer using computed tomography (also called CT scans) saves lives by increasing the number of patients who are diagnosed before their lung cancer has spread. While this represents an important victory in our battle with lung cancer, lung cancer screening using CT scans is not perfect. The most important weakness of CT scanning for lung cancer screening is that over 95% of patients who are found to have a lung nodule that is suspicious for lung cancer are later found not to have lung cancer. Such a high frequency of false positive test results induces anxiety in patients and their families, requires additional expensive tests, and may result in harm if follow-up studies lead to a complication. We propose to develop a new approach for lung cancer screening that is minimally invasive, can discover very early lung cancers, and is less expensive than CT scanning. We will compare two approaches. First, we will try to detect tiny amounts of DNA that are released into the blood stream by lung cancers and end up in the urine. Second, we will test if we can improve the ability of a minimally invasive intervention called bronchoscopy that is frequently performed to follow up nodules found on CT scans but similarly looking for traces of tumor DNA in washings done during this procedure. We have performed preliminary experiments that suggest our approach is feasible and now plan to evaluate it in a pilot clinical study. If successful, our method could be used together with CT scanning in order to reduce the number of unnecessary follow-up tests or could eventually even replace CT scans as the primary lung cancer screening test. If so, it could reduce the risk of CT scan-induced cancers, would be more economical, and could increase the number of patients who can be screened.
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