November 28, 2011 — A series of letters to the New England Journal of Medicine has raised questions about the results of the National Lung Screening Trial (NLST).
The NSLT results were published several months ago (N Engl J Med. 2011;365:395-409), but were initially released to the public in October 2010 when the trial was halted early because of the survival benefit seen with computed tomography (CT) scanning. At a median follow-up of 6.5 years, the 53,000-person trial found a 20% reduction in deaths from lung cancer in current and former heavy smokers screened with low-dose helical CT, compared with those screened with chest x-ray (P = .004).
"This was a large randomized clinical trial and it provides the strongest level of evidence that can be obtained," said Arnold J. Rotter, MD, from the City of Hope Hospital in Duarte, California, in a recent interview with Medscape Medical News. Dr. Rotter is one of the authors of the new guidelines from the National Comprehensive Cancer Network that "strongly recommend" screening the high-risk group of heavy smokers.
Debate about lung cancer screening has raged on for several years now, sparked by results from the International Early Lung Cancer Action Program (I-ELCAP) study. The main criticism of I-ELCAP was that it was not a randomized trial, and experts urged all concerned to wait for results from randomized studies.
Now that the NLST results are in and are overwhelmingly positive for lung cancer screening with low-dose CT in high-risk individuals, there should be an end to these debates, Dr. Rotter said. But the debate continues, as recently reported by Medscape Medical News.
The debate in the series of letters includes questions about the benefits and harms of lung cancer screening.
"It seems to us that the balance between the benefits and harms of screening is tipped toward the latter," write Bruno Heleno, MD, and Jakob Rasmussen, MD, from the Research Unit for General Practice, Copenhagen, Denmark.
According to the NSLT, in a hypothetical population of 1000 healthy heavy smokers (current or former), screening with low-dose CT, as opposed to chest x-ray, would avert 5 deaths, 3 of which would be due to lung cancer, they note.
However, CT screening would also result in 231 people with at least 1 positive result, 22 additional invasive procedures, 18 additional surgeries, and 6 nonfatal complications resulting from these procedures. Plus, the extent of psychosocial harm as a consequence of false-positive results is still unaccounted for, they write.
Other letters highlight the problem of overdiagnosis, which Peter Bach, MD, MAPP, from the Memorial Sloan-Kettering Cancer Center in New York City, says is greater than was reported. The NSLT researchers calculated the rate of overdiagnosis to be 13%, and described this as "not large," but they did not use the appropriate denominator, he asserts. He says the rate is nearly twice that — 25% — and notes that several other studies have pegged the overdiagnosis rate at about 20% to 25%.
The NSLT researchers reply that they did not report formal estimates of overdiagnosis. Longer follow-up is needed, as is a discussion of how to estimate overdiagnosis with CT screening, compared with chest x-ray, which also has a potential for overdiagnosis, write NSLT researchers Christine Berg, MD, from the National Cancer Institute, Bethesda, Maryland, and Denise Aberle, MD, from the University of California at Los Angeles.
The issue of cost effectiveness is raised in a letter from Michael Kohn, MD, MPP, from the University of California at San Francisco. Using a "back of an envelope" analysis, he calculates that according to the NSLT results, the number needed to screen to prevent 1 death from lung cancer is 300.
However, to prevent that 1 death from lung cancer, these 300 people would have to undergo 900 screening CT scans (at a total cost of around $300,000) and about 85 additional positive screening tests (around $425,000), he explains. This gives an approximate total cost of $725,000, which does not include any cost of treatment or distress caused by false-positive results.
The NSTL researchers say that these such calculations are "of interest," and add that because "the average duration of life lost to lung cancer is about 15 years, Kohn's estimate is equivalent to about $48,000 per year of life gained."
Drs. Berg and Aberle note that these issues of overdiagnosis and cost effectiveness, as well as that of interval cancers — which are mentioned in another letter — are all "important issues for further interpretation of our primary result, a reduction in lung-cancer-specific mortality after low-dose CT screening." They add that, in collaboration with other researchers, they are currently involved in modeling studies that will allow the evaluation of benefits/risk ratios.
N Engl J Med. 2011;365:2035-2038. Abstract
The NSLT results were published several months ago (N Engl J Med. 2011;365:395-409), but were initially released to the public in October 2010 when the trial was halted early because of the survival benefit seen with computed tomography (CT) scanning. At a median follow-up of 6.5 years, the 53,000-person trial found a 20% reduction in deaths from lung cancer in current and former heavy smokers screened with low-dose helical CT, compared with those screened with chest x-ray (P = .004).
"This was a large randomized clinical trial and it provides the strongest level of evidence that can be obtained," said Arnold J. Rotter, MD, from the City of Hope Hospital in Duarte, California, in a recent interview with Medscape Medical News. Dr. Rotter is one of the authors of the new guidelines from the National Comprehensive Cancer Network that "strongly recommend" screening the high-risk group of heavy smokers.
Debate about lung cancer screening has raged on for several years now, sparked by results from the International Early Lung Cancer Action Program (I-ELCAP) study. The main criticism of I-ELCAP was that it was not a randomized trial, and experts urged all concerned to wait for results from randomized studies.
Now that the NLST results are in and are overwhelmingly positive for lung cancer screening with low-dose CT in high-risk individuals, there should be an end to these debates, Dr. Rotter said. But the debate continues, as recently reported by Medscape Medical News.
The debate in the series of letters includes questions about the benefits and harms of lung cancer screening.
"It seems to us that the balance between the benefits and harms of screening is tipped toward the latter," write Bruno Heleno, MD, and Jakob Rasmussen, MD, from the Research Unit for General Practice, Copenhagen, Denmark.
According to the NSLT, in a hypothetical population of 1000 healthy heavy smokers (current or former), screening with low-dose CT, as opposed to chest x-ray, would avert 5 deaths, 3 of which would be due to lung cancer, they note.
However, CT screening would also result in 231 people with at least 1 positive result, 22 additional invasive procedures, 18 additional surgeries, and 6 nonfatal complications resulting from these procedures. Plus, the extent of psychosocial harm as a consequence of false-positive results is still unaccounted for, they write.
Other letters highlight the problem of overdiagnosis, which Peter Bach, MD, MAPP, from the Memorial Sloan-Kettering Cancer Center in New York City, says is greater than was reported. The NSLT researchers calculated the rate of overdiagnosis to be 13%, and described this as "not large," but they did not use the appropriate denominator, he asserts. He says the rate is nearly twice that — 25% — and notes that several other studies have pegged the overdiagnosis rate at about 20% to 25%.
The NSLT researchers reply that they did not report formal estimates of overdiagnosis. Longer follow-up is needed, as is a discussion of how to estimate overdiagnosis with CT screening, compared with chest x-ray, which also has a potential for overdiagnosis, write NSLT researchers Christine Berg, MD, from the National Cancer Institute, Bethesda, Maryland, and Denise Aberle, MD, from the University of California at Los Angeles.
The issue of cost effectiveness is raised in a letter from Michael Kohn, MD, MPP, from the University of California at San Francisco. Using a "back of an envelope" analysis, he calculates that according to the NSLT results, the number needed to screen to prevent 1 death from lung cancer is 300.
However, to prevent that 1 death from lung cancer, these 300 people would have to undergo 900 screening CT scans (at a total cost of around $300,000) and about 85 additional positive screening tests (around $425,000), he explains. This gives an approximate total cost of $725,000, which does not include any cost of treatment or distress caused by false-positive results.
The NSTL researchers say that these such calculations are "of interest," and add that because "the average duration of life lost to lung cancer is about 15 years, Kohn's estimate is equivalent to about $48,000 per year of life gained."
Drs. Berg and Aberle note that these issues of overdiagnosis and cost effectiveness, as well as that of interval cancers — which are mentioned in another letter — are all "important issues for further interpretation of our primary result, a reduction in lung-cancer-specific mortality after low-dose CT screening." They add that, in collaboration with other researchers, they are currently involved in modeling studies that will allow the evaluation of benefits/risk ratios.
N Engl J Med. 2011;365:2035-2038. Abstract
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