Correspondence
main researcher, has been strongly criticised for not having a comparator group and for its questionable methods. The Comment does not include the results of other important randomised trials on low-dose CT for lung cancer screening, such as the Danish study, ITALUNG, or DANTE, among others. Further, the Comment does not provide a fair view of present knowledge. For example, Mulshine and Henschke note that interval cancers are due to non-compliance or errors, and do not mention the characteristics of interval cancers recorded in the NLST. What about the possibility of fast-growing tumours and the fact that roughly 66% of interval cancers diagnosed in the NLST are stages III and IV?4 The authors also fail to mention the 18% of overdiagnosed cancers with low-dose CT recorded in the NLST.5,6 Doctors still do not know how to manage positive findings obtained from screening (eg, screening interval, volumetric assessment vs diametric assessment, reasons for interval cancers), especially for nodules with intermediate pre-test lung cancer probability. Do we really have enough information about benefits versus harms to implement a populationbased lung cancer screening programme with low-dose CT? We declare no competing interests.
Alberto Ruano-Ravina, Mónica Pérez-Ríos [email protected] Department of Preventive Medicine and Public Health, University of Santiago de Compostela, Santiago de Compostela 15782, Spain; CIBER de Epidemiología y Salud Pública, CIBERESP, Madrid, Spain 1
2
3
e4
Mulshine JL, Henschke CI. Lung cancer screening: achieving more by intervening less. Lancet Oncol 2014; 15: 1284–85. Horeweg N, van Rosmalen J, Heuvelmans MA, et al. Lung cancer probability in patients with CT-detected pulmonary nodules: a prespecified analysis of data from the NELSON trial of low-dose CT screening. Lancet Oncol 2014; 15: 1332–41. Horeweg N, Scholten ET, de Jong PA, et al. Detection of lung cancer through low-dose CT screening (NELSON): a prespecified analysis of screening test performance and interval cancers. Lancet Oncol 2014; 15: 1342–50.
4
5
6
National Lung Screening Trial Research Team, Aberle DR, Adams AM, Berg CD, et al. Reduced lung-cancer mortality with low-dose computed tomographic screening. N Engl J Med 2011; 365: 395–409. Patz EF Jr, Pinsky P, Gatsonis C, et al. Overdiagnosis in low-dose computed tomography screening for lung cancer. JAMA Intern Med 2014; 174: 269–74. Ruano-Ravina A, Heleno B, Fernández-Villar A. Lung cancer screening with low-dose CT (LDCT), or when a public health intervention is beyond the patient’s benefit. J Epidemiol Community Health 2014; published online Aug 19. DOI:10.1136/jech-2014-204293.
Author’s reply We appreciate Mónica Ruano-Ravina and Alberto Pérez-Ríos’ remarks on our recent Comment.1 The title of our Comment mirrored the findings of the NELSON study,2,3 which showed that restriction of diagnostic work-up to large pulmonary nodules increases the efficiency of the screening diagnostic work-up by reducing the number of non-productive work-ups. These results support the earlier findings of Yip and co-workers.4 This kind of process improvement research does not need a randomised trial to be valid. Although only a few of the nodules less than 100 mm³ in volume or 5 mm in diameter are cancers, the typical volume doubling times of aggressive cancers range from 30 to 360 days, consistent with a range of two to 24 for volume doublings in 2 years, suggesting that followup of CT detected nodules in 2 years rather than in 1 year might be unwise. Investigators of the NELSON study reported protocol non-compliance and human errors of detection and interpretation that led to their reported interim cancers. The National Lung Screening Trial5 does not provide the timing data from the last screenings of their interval cancers for further assessment. Further research is needed before the recommended annual screening is replaced with screening every 2 years. Ruano-Ravina and Pérez-Ríos’ concluding comment about screening implementation is addressed by the comprehensive data synthesis by the US Preventive Services Task
Force (USPSTF).6 This report gives an authoritative review of the scientific basis of screening from an analysis of more than 8000 publications. This information formed the basis for the final B recommendation from USPSTF and more recently for the provisional position from the Center for Medicare and Medicaid recommending reimbursement for low-dose CT screening in high-risk smokers in the USA. Expectations in different national settings might vary, but it seems that national implementation of annual screening for the world’s most lethal cancer will soon begin. I declare no competing interests.
James L Mulshine [email protected] Rush University Medical Center, Chicago, IL 60612, USA 1
2
3
4
5
6
Mulshine JL, Henschke CI. Lung cancer screening: achieving more by intervening less. Lancet Oncol 2014; 15: 1284–85. Horeweg N, van Rosmalen J, Heuvelmans MA, et al. Lung cancer probability in patients with CT-detected pulmonary nodules: a prespecifi ed analysis of data from the NELSON trial of low-dose CT screening. Lancet Oncol 2014; 15: 1332–41. Horeweg N, Scholten ET, de Jong PA, et al. Detection of lung cancer through low-dose CT screening (NELSON): a prespecifi ed analysis of screening test performance and interval cancers. Lancet Oncol 2014; 15: 1342–50. Yip R, Henschke CI, Yankelevitz DF, Smith JP. CT screening for lung cancer: alternative definitions of positive test result based on the national lung screening trial and international early lung cancer action program databases. Radiology 2014; 273: 591–96. Aberle DR, DeMello S, Berg CD, et al, for the National Lung Screening Trial Research Team. Results of the two incidence screenings in the national lung screening trial. N Engl J Med 2013; 369: 920–31. Humphrey L, Deffebach M, Pappas M, et al. Screening for lung cancer: systematic review to update the US Preventive Services Task Force recommendation statement. Rockville, MD: Agency for Healthcare Research and Quality, 2013.
Silencing the voice of scientific reason In view of the central role of science in underpinning advances in cancer research and cancer care, the decision by the new President of the www.thelancet.com/oncology Vol 16 January 2015
main researcher, has been strongly criticised for not having a comparator group and for its questionable methods. The Comment does not include the results of other important randomised trials on low-dose CT for lung cancer screening, such as the Danish study, ITALUNG, or DANTE, among others. Further, the Comment does not provide a fair view of present knowledge. For example, Mulshine and Henschke note that interval cancers are due to non-compliance or errors, and do not mention the characteristics of interval cancers recorded in the NLST. What about the possibility of fast-growing tumours and the fact that roughly 66% of interval cancers diagnosed in the NLST are stages III and IV?4 The authors also fail to mention the 18% of overdiagnosed cancers with low-dose CT recorded in the NLST.5,6 Doctors still do not know how to manage positive findings obtained from screening (eg, screening interval, volumetric assessment vs diametric assessment, reasons for interval cancers), especially for nodules with intermediate pre-test lung cancer probability. Do we really have enough information about benefits versus harms to implement a populationbased lung cancer screening programme with low-dose CT? We declare no competing interests.
Alberto Ruano-Ravina, Mónica Pérez-Ríos [email protected] Department of Preventive Medicine and Public Health, University of Santiago de Compostela, Santiago de Compostela 15782, Spain; CIBER de Epidemiología y Salud Pública, CIBERESP, Madrid, Spain 1
2
3
e4
Mulshine JL, Henschke CI. Lung cancer screening: achieving more by intervening less. Lancet Oncol 2014; 15: 1284–85. Horeweg N, van Rosmalen J, Heuvelmans MA, et al. Lung cancer probability in patients with CT-detected pulmonary nodules: a prespecified analysis of data from the NELSON trial of low-dose CT screening. Lancet Oncol 2014; 15: 1332–41. Horeweg N, Scholten ET, de Jong PA, et al. Detection of lung cancer through low-dose CT screening (NELSON): a prespecified analysis of screening test performance and interval cancers. Lancet Oncol 2014; 15: 1342–50.
4
5
6
National Lung Screening Trial Research Team, Aberle DR, Adams AM, Berg CD, et al. Reduced lung-cancer mortality with low-dose computed tomographic screening. N Engl J Med 2011; 365: 395–409. Patz EF Jr, Pinsky P, Gatsonis C, et al. Overdiagnosis in low-dose computed tomography screening for lung cancer. JAMA Intern Med 2014; 174: 269–74. Ruano-Ravina A, Heleno B, Fernández-Villar A. Lung cancer screening with low-dose CT (LDCT), or when a public health intervention is beyond the patient’s benefit. J Epidemiol Community Health 2014; published online Aug 19. DOI:10.1136/jech-2014-204293.
Author’s reply We appreciate Mónica Ruano-Ravina and Alberto Pérez-Ríos’ remarks on our recent Comment.1 The title of our Comment mirrored the findings of the NELSON study,2,3 which showed that restriction of diagnostic work-up to large pulmonary nodules increases the efficiency of the screening diagnostic work-up by reducing the number of non-productive work-ups. These results support the earlier findings of Yip and co-workers.4 This kind of process improvement research does not need a randomised trial to be valid. Although only a few of the nodules less than 100 mm³ in volume or 5 mm in diameter are cancers, the typical volume doubling times of aggressive cancers range from 30 to 360 days, consistent with a range of two to 24 for volume doublings in 2 years, suggesting that followup of CT detected nodules in 2 years rather than in 1 year might be unwise. Investigators of the NELSON study reported protocol non-compliance and human errors of detection and interpretation that led to their reported interim cancers. The National Lung Screening Trial5 does not provide the timing data from the last screenings of their interval cancers for further assessment. Further research is needed before the recommended annual screening is replaced with screening every 2 years. Ruano-Ravina and Pérez-Ríos’ concluding comment about screening implementation is addressed by the comprehensive data synthesis by the US Preventive Services Task
Force (USPSTF).6 This report gives an authoritative review of the scientific basis of screening from an analysis of more than 8000 publications. This information formed the basis for the final B recommendation from USPSTF and more recently for the provisional position from the Center for Medicare and Medicaid recommending reimbursement for low-dose CT screening in high-risk smokers in the USA. Expectations in different national settings might vary, but it seems that national implementation of annual screening for the world’s most lethal cancer will soon begin. I declare no competing interests.
James L Mulshine [email protected] Rush University Medical Center, Chicago, IL 60612, USA 1
2
3
4
5
6
Mulshine JL, Henschke CI. Lung cancer screening: achieving more by intervening less. Lancet Oncol 2014; 15: 1284–85. Horeweg N, van Rosmalen J, Heuvelmans MA, et al. Lung cancer probability in patients with CT-detected pulmonary nodules: a prespecifi ed analysis of data from the NELSON trial of low-dose CT screening. Lancet Oncol 2014; 15: 1332–41. Horeweg N, Scholten ET, de Jong PA, et al. Detection of lung cancer through low-dose CT screening (NELSON): a prespecifi ed analysis of screening test performance and interval cancers. Lancet Oncol 2014; 15: 1342–50. Yip R, Henschke CI, Yankelevitz DF, Smith JP. CT screening for lung cancer: alternative definitions of positive test result based on the national lung screening trial and international early lung cancer action program databases. Radiology 2014; 273: 591–96. Aberle DR, DeMello S, Berg CD, et al, for the National Lung Screening Trial Research Team. Results of the two incidence screenings in the national lung screening trial. N Engl J Med 2013; 369: 920–31. Humphrey L, Deffebach M, Pappas M, et al. Screening for lung cancer: systematic review to update the US Preventive Services Task Force recommendation statement. Rockville, MD: Agency for Healthcare Research and Quality, 2013.
Silencing the voice of scientific reason In view of the central role of science in underpinning advances in cancer research and cancer care, the decision by the new President of the www.thelancet.com/oncology Vol 16 January 2015
