“Lung cancer statistics overwhelm the favorable results achieved in the past quarter century in the treatment of other malignancies and cause the press and the public alike to believe that in spite of massive funding, little progress is being made, and the war on cancer is being lost.”
Reginald F. Munden and David E. Bragg1
If current rates continue, more than 1 million Americans will die of lung cancer in the next 7 years.2 As the 5-year survival rate is 49% in patients whose tumors are localized when discovered, while the rate for all patients is 14%, screening for lung cancer might seem to be a good idea, especially in view of the success with screening for prostate and breast cancer. But not so fast: does lung cancer screening improve patient outcome?
The first question is whether imaging can detect a lung cancer early enough to do any good. A 5-mm cancer already contains 108 cells, putting it well on its way to the estimated lethal disease burden of 1,012 cells.3 Moreover, cancers arising in the highly vascular tissue of the lungs can start producing metastases when they measure only 1 to 2 mm. Perhaps this explains why survival rates are the same when the primary tumor measures 3 cm as when it is only 1 cm.4 As Reginald F. Munden, MD, of the Division of Diagnostic Imaging at The University of TexasMD Anderson Cancer Center in Houston recently stressed, “Lung cancer is a systemic disease.” Great care is needed to be sure any apparent improvement in survival associated with screening is not simply a reflection of lead-time bias.
A second question is what risks are being imposed by repeated CT scans. Even with the low-dose protocols, which deliver 0.65 mSv (versus 5.8 mSv for a standard diagnostic scan), the patient receives 10 times the radiation he or she would receive from a chest radiograph. “Low dose” does not mean benign. The repeated use of multidetector CT scanners to improve resolution presumably further increases the risk of radiation-induced cancers in patients, as these scanners deliver doses as much as 50% higher than conventional helical scanners.5
A third question is what costs of false-negative and false-positive studies are acceptable. In the Nagano trial,6 32 of the 88 lung cancers eventually found were overlooked on the initial screening studies! Computer-aided detection found 84% of these missed lesions at the cost of one false-positive finding per section.7 Indeed, nodules are discovered by CT screening in as many as 69% of patients, leading to the cost, morbidity, and patient anxiety of additional studies, yet even in high-risk populations, most of these nodules prove to be benign.
A fourth question is whether the malpractice and ethical issues can be dealt with satisfactorily. Worries have been expressed about conflicts of interest if a radiologist advocates screening and then does the scan and about the duties of a radiologist to a self-referred patient. “Radiologists who solicit patients to undergo screening radiologic examinations without being referred by a primary care physician will find themselves placed in the position of acting as primary care physician,” noted Leonard Berlin, MD, of the Department of Radiology at Rush North Shore Hospital in Skokie, Ill, and Rush Medical College in Chicago.5
Because of these and other questions, there are calls to restrict lung cancer screening to controlled clinical trials such as the 500,000-person National Lung Screening Trial being directed by the National Institutes of Health. Thomas E. Hartman and Stephen J. Swensen of the Mayo Clinic recently reminded radiologists of the sorry history of autologous bone-marrow transplantation for advanced breast cancer. The practice was widely used (and pushed in the popular press by patient advocates) before clinical trials of its efficacy were completed. When the data were mature, they proved that the highly morbid treatment was no more effective than less toxic measures. The number of women whose lives were shortened by the procedure is a matter for speculation, but clearly, it was large.
“If lung cancer screening with low-dose CT is implemented without the scientific data to support it, how many billions of dollars & will be spent and how many people will suffer significant morbidity or mortality for evaluation of benign disease [that would not have been worked up] were it not for an unproven screening test?” Hartman and Swensen wondered. “We must be sure that lung cancer screening&provides benefits that outweigh the risk.”2
— J.G. Bronson
- Munden RF, Bragg DE. Primary malignancies of the thorax. In: Bragg DG, Rubin P, Hricak H, eds. Oncologic Imaging. Philadelphia: WB Saunders; 2002:313.
- Hartman TE, Swensen SJ. Lung cancer screening with low-dose computed tomography. Semin Roentgenol. 2003;38:34â€”38.
- DeVita VT Jr, Young RC, Canellos GP. Combination versus single agent chemotherapy: a review of the basis for selection of drug treatment of cancer. Cancer. 1975;35:98â€”110.
- Patz EF Jr, Goodman PC, Bepler G. Screening for lung cancer. N Engl J Med. 2000;343:1627â€”1633.
- Berlin L. Medicolegal and ethical issues in radiologic screening. Semin Roentgenol. 2003;38:77â€”86.
- Li F, Sone S, Abe H, MacMahon H, Armato SG III, Doi K. Lung cancers missed at low-dose helical CT screening in a general population: comparison of clinical, histopathologic, and imaging findings. Radiology. 2002;225:673â€”683.
- Armato SG III, Li F, Giger ML, MacMahon H, Sone S, Doi K. Lung cancer: performance of automated lung nodule detection applied to cancers missed in a CT screening program. Radiology. 2002;225:685â€”692.