Cancer Prevention and Health Disparities Among Minorities

Helicobacter pylori and Gastric Cancer

Issues & Insights

Lung Cancer Screening: Where Are We Now?

News From The NCI

The Media's Role in Cancer Prevention

Federal Legislation

State Legislation

Cancer Prevention Clinical Trials

	James L. Mulshine, MD
	Elizabeth E. Warner, MD

James L. Mulshine, MD
Head
Intervention Section
Cell and Cancer Biology Branch
Co-chair
Upper Aerodigestive Chemoprevention Faculty
Center for Cancer Research
National Cancer Institute
National Institutes of Health
Bethesda, Maryland

Elizabeth E. Warner, MD
Department of Surgery
Georgetown University Hospital
Washington, DC
Visiting Researcher
Intervention Section
Cell and Cancer Biology Branch
Upper Aerodigestive Chemoprevention Faculty
Center for Cancer Research
National Cancer Institute
National Institutes of Health
Bethesda, Maryland

Last year, there were approximately 171,900 new cases of lung cancer and 157,200 deaths due to this disease in the US alone.(1) The year 2003 also had the unfortunate distinction of being the first year that the number of lung cancer deaths outstripped the number of coronary artery disease-related deaths directly attributable to tobacco use in this country.(2) There are over 90 million current and former smokers in the US at risk for developing lung cancer. Should they develop lung cancer, they face a 5-year survival rate of 15%. Clearly, lung cancer remains a public health crisis in this country.(3) While it is important to continue efforts aimed at smoking prevention and cessation, focusing energy on these goals alone neglects the 50 million people who have already quit smoking but remain at an elevated risk for developing lung cancer. Meanwhile, lung cancer deaths among former and never-smokers in this country continue to outnumber cancer deaths from breast and colon cancer combined. Developing new methods of identifying lung cancer at an early stage could lead to a reduction in cancer deaths.

Lung cancer's lethality is due in large part to the fact that, at the time of presentation, it is usually already widely metastatic and, therefore, not curable. Efforts have been made in the past to detect lung cancer at an earlier stage with the belief that earlier diagnosis may lead to improved curability. Studies, such as the Mayo Lung Project in the early 1980s, examined the use of serial chest x-ray as a potential screening tool for the early detection of lung cancer. However, it was concluded that, while some cancers were indeed found in advance of symptoms, only 30% were still stage I at detection, and an overall lung cancer-related mortality benefit was not evident.(4)

Rapidly evolving improvements in imaging technology, however, have raised this issue yet again. CT scanning has evolved remarkably over the last decade due to faster image acquisition capabilities coupled with massive improvements in microprocessing power.(5) Currently available spiral CT scanners are standard instruments in most hospitals and clinics in the developed world. These instruments can image the entire thorax with <1 mm slices thickness in about 20 seconds (within the duration of a single breath-hold) using a radiation dose comparable to that of a standard chest x-ray. Rapid advances in resolution and reconstruction technologies have made it possible to frequently detect lung nodules in the subcentimeter range, which greatly exceeds the capabilities of conventional chest x-ray. The evolving field of computer-assisted diagnosis, already widely used in assisting with mammography reading and cervical cytopathology examination, is showing promise as a means to enhance the detection of small, suspicious nodules while easing the potentially crushing burden that a huge number of new screening scans would present to the radiology community. The first premarket approval (PMA) for this lung indication was recently reviewed by a Food and Drug Administration (FDA) device panel and recommended for approval with the provision of conducting additional postmarketing evaluations of efficacy. The R2 ImageChecker CT Workstation LN-1000 was designed as a second-reader system. Computer-assisted diagnostic (CAD) systems also are being developed by other CT instrument manufacturers.

Some members of the medical community are concerned that detection of smaller primary lung cancers will not ultimately lead to a mortality benefit,(6,7). Other epithelial cancers behave in a relatively predictable way, beginning as localized phenomena with the likelihood of metastases increasing with time and size. A larger body of experience has demonstrated this same pattern for lung cancer. Increasing metastatic frequency correlates with increasing size and growing evidence indicates that more favorable outcomes are associated with detecting smaller primary cancers.(8-14) Meanwhile, groups such as the Early Lung Cancer Action Project (ELCAP) at the Weill Cornell Medical Center in New York and the Anti-Lung Cancer Association in Japan have demonstrated the ability to detect stage Ia lung cancer with spiral CT in better than 70% of patients with lung cancer.(15-17)

While several groups have demonstrated the ability of spiral CT to detect early stage lung cancer, there is no evidence yet to show that this improvement results in an improved outcome in terms of reducing deaths due to lung cancer. However, the National Cancer Institute (NCI) has launched the National Lung Screening Trial (NLST), a major randomized trial of conventional chest x-ray versus spiral CT scan designed to evaluate their impact on lung cancer-related mortality (NLST-www.cancer.gov/nlst ). This trial has recently completed accrual of 50,000 subjects. Each subject is to receive either a chest X-ray or a spiral CT once a year for three years and then to be followed for their clinical outcome. Trial results will not be available until definitive follow-up information is available. The Dutch also have recently launched a large national randomized screening trial.

In the meantime, a great deal of research effort is required to optimize the downstream management of lung cancer to decrease morbidity as well as cost. The surgical management of lung cancer, for example, typically involves a fairly extensive operation--thoracotomy incision with an anatomic resection in the form of a lobectomy or pneumonectomy. Investigators in the past concluded that doing a lesser stage la resection exposed patients to an unacceptably high risk of recurrence.(18-20) This issue may warrant reevaluation, in part, because the average size of CT-detected lung cancer is so much smaller than with typical chest X-ray detected lung cancer. There is also a significant risk of eventually developing second or third primary lung cancers mandating the need to preserve lung parenchyma.(21)

Ongoing technological advances in the fields of diagnostic imaging and CAD diagnosis have provided more sensitive tools to detect early lung cancer. While lung cancer remains the most lethal cancer in the world, the hope for major improvement in this disease has led to new randomized lung cancer screening trials. Complementary research into strategies for downstream management of CT-detected early lung cancer may also allow for improved screening outcomes.

References

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