Lung-Cancer Screening
http://www.100md.com
《新英格兰医药杂志》
To the Editor: Mulshine and Sullivan (June 30 issue)1 note the high proportion of cancers detected by screening at stage 1. As they acknowledge, however, this proportion cannot be used to indicate the efficacy of screening, which requires a corresponding reduction in the absolute number of advanced lung cancers. Earlier controlled trials, using standard radiography,2,3 failed to achieve this effect. Preliminary analyses of trials that used low-dose computed tomography (CT),4,5 although inconclusive, show no diminution in advanced cancers in the incidence screens as compared with controls. This failure may reflect the proximal endobronchial origin of many cancers (for which CT scanning is relatively insensitive) or the rapid growth of advanced lung cancers.
Contrary to the suggestion of the authors, overdiagnosis of clinically insignificant lung cancers remains a concern with screening. Overdiagnosed lung cancers need not differ biologically from lethal cancers: a tumor of 0.5 g with a diameter of 1 cm and a volume-doubling time of 300 days (the mean value for malignant nodules<3 cm) would require 8 years to achieve a lethal size of 10 cm,6 during which interval some elderly people who smoke will die from competing illnesses.
Jerome M. Reich, M.D.
Earl A. Chiles Research Institute
Portland, OR 97213
reichje@dnamail.com
References
Mulshine JL, Sullivan DC. Lung cancer screening. N Engl J Med 2005;352:2714-2720.
Fontana RS, Sanderson DR, Woolner LB, Taylor WF, Miller WE, Muhm JR. Lung cancer screening: the Mayo program. J Occup Med 1986;28:746-750.
Kub?k A, Parkin DM, Khlat M, Erban J, Polak J, Adamec M. Lack of benefit from semi-annual screening for cancer of the lung: follow-up report of a randomized controlled trial on a population of high-risk males in Czechoslovakia. Int J Cancer 1990;45:26-33.
Patz EF Jr, Swensen SJ, Herndon JE II. Estimate of lung cancer mortality from low-dose spiral computed tomography screening trials: implication for current mass screening recommendations. J Clin Oncol 2004;22:2202-2206.
Gohagan JK, Marcus PM, Fagerstrom RM, et al. Final results of the Lung Screening Study, a randomized feasibility study of spiral CT versus chest X-ray screening for lung cancer. Lung Cancer 2005;47:9-15.
Weiss W. A practical model of tumor growth. J Respir Dis 1980;1:41-49.
The authors reply: The issue of overdiagnosis has recently dominated discussions regarding lung cancer screening. This is ironic, since with standard approaches, stage 1 lung cancer is found in only 15 percent of cases, suggesting that late diagnosis is the more urgent problem.
Dr. Reich cites two recent papers to support his position on overdiagnosis. The first1 involved a methodologically suspect comparison of the results of two independent screening populations separated by time, place, and eligibility criteria. The second citation2 was from a pilot study evaluating the feasibility of randomization for the National Lung Screening Trial. These reports involved clinical trials not designed to evaluate instances of overdiagnosis.
Regarding Dr. Reich's theoretical observations about doubling time and lethal tumor burden, there is no existing information suggesting a benign, eight-year natural history for 1-cm cancers detected with CT screening. Early-stage, untreated primary cancers (<10 cm) detected with CT screening reported in the Japanese and the Cornell studies were typically fatal.3,4 Given the lethality of lung cancer, we should focus on responsibly detecting and managing it at an early stage.
James L. Mulshine, M.D.
National Cancer Institute
Bethesda, MD 20892
james_l_mulshine@rush.edu
Daniel C. Sullivan, M.D.
National Cancer Institute
Rockville, MD 20852
References
Patz EF Jr, Swensen SJ, Herndon JE II. Estimate of lung cancer mortality from low-dose spiral computed tomography screening trials: implication for current mass screening recommendations. J Clin Oncol 2004;22:2202-2206.
Gohagan JK, Marcus PM, Fagerstrom RM, et al. Final results of the Lung Screening Study, a randomized feasibility study of spiral CT versus chest X-ray screening for lung cancer. Lung Cancer 2005;47:9-15.
Sato M, Saito Y, Endo C, et al. The natural history of radiographically occult bronchogenic squamous cell carcinoma: a retrospective study of overdiagnosis bias. Chest 2004;126:108-113.
Wisnivesky JP, Bonomi M, Henschke C, Iannuzzi M, McGinn T. Radiation therapy for the treatment of unresected stage I-II non-small cell lung cancer. Chest 2005;128:1461-1467.
Contrary to the suggestion of the authors, overdiagnosis of clinically insignificant lung cancers remains a concern with screening. Overdiagnosed lung cancers need not differ biologically from lethal cancers: a tumor of 0.5 g with a diameter of 1 cm and a volume-doubling time of 300 days (the mean value for malignant nodules<3 cm) would require 8 years to achieve a lethal size of 10 cm,6 during which interval some elderly people who smoke will die from competing illnesses.
Jerome M. Reich, M.D.
Earl A. Chiles Research Institute
Portland, OR 97213
reichje@dnamail.com
References
Mulshine JL, Sullivan DC. Lung cancer screening. N Engl J Med 2005;352:2714-2720.
Fontana RS, Sanderson DR, Woolner LB, Taylor WF, Miller WE, Muhm JR. Lung cancer screening: the Mayo program. J Occup Med 1986;28:746-750.
Kub?k A, Parkin DM, Khlat M, Erban J, Polak J, Adamec M. Lack of benefit from semi-annual screening for cancer of the lung: follow-up report of a randomized controlled trial on a population of high-risk males in Czechoslovakia. Int J Cancer 1990;45:26-33.
Patz EF Jr, Swensen SJ, Herndon JE II. Estimate of lung cancer mortality from low-dose spiral computed tomography screening trials: implication for current mass screening recommendations. J Clin Oncol 2004;22:2202-2206.
Gohagan JK, Marcus PM, Fagerstrom RM, et al. Final results of the Lung Screening Study, a randomized feasibility study of spiral CT versus chest X-ray screening for lung cancer. Lung Cancer 2005;47:9-15.
Weiss W. A practical model of tumor growth. J Respir Dis 1980;1:41-49.
The authors reply: The issue of overdiagnosis has recently dominated discussions regarding lung cancer screening. This is ironic, since with standard approaches, stage 1 lung cancer is found in only 15 percent of cases, suggesting that late diagnosis is the more urgent problem.
Dr. Reich cites two recent papers to support his position on overdiagnosis. The first1 involved a methodologically suspect comparison of the results of two independent screening populations separated by time, place, and eligibility criteria. The second citation2 was from a pilot study evaluating the feasibility of randomization for the National Lung Screening Trial. These reports involved clinical trials not designed to evaluate instances of overdiagnosis.
Regarding Dr. Reich's theoretical observations about doubling time and lethal tumor burden, there is no existing information suggesting a benign, eight-year natural history for 1-cm cancers detected with CT screening. Early-stage, untreated primary cancers (<10 cm) detected with CT screening reported in the Japanese and the Cornell studies were typically fatal.3,4 Given the lethality of lung cancer, we should focus on responsibly detecting and managing it at an early stage.
James L. Mulshine, M.D.
National Cancer Institute
Bethesda, MD 20892
james_l_mulshine@rush.edu
Daniel C. Sullivan, M.D.
National Cancer Institute
Rockville, MD 20852
References
Patz EF Jr, Swensen SJ, Herndon JE II. Estimate of lung cancer mortality from low-dose spiral computed tomography screening trials: implication for current mass screening recommendations. J Clin Oncol 2004;22:2202-2206.
Gohagan JK, Marcus PM, Fagerstrom RM, et al. Final results of the Lung Screening Study, a randomized feasibility study of spiral CT versus chest X-ray screening for lung cancer. Lung Cancer 2005;47:9-15.
Sato M, Saito Y, Endo C, et al. The natural history of radiographically occult bronchogenic squamous cell carcinoma: a retrospective study of overdiagnosis bias. Chest 2004;126:108-113.
Wisnivesky JP, Bonomi M, Henschke C, Iannuzzi M, McGinn T. Radiation therapy for the treatment of unresected stage I-II non-small cell lung cancer. Chest 2005;128:1461-1467.