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Ma et al have estimated that if every one of the current or former smokers in the United States who has accumulated 30 pack-years began low-dose screening with computed tomography (CT), each year approximately 12,000 deaths due to lung cancer could be delayed or averted.1 These estimates are based on the highly successful results of the National Lung Screening Trial (NLST) that were published last year.2 What does this tell us about public health efforts related to lung cancer? Can we improve on the estimated 20% reduction in lung cancer mortality or is this the limit of our abilities? Is this hopeful intervention the best that our public health efforts can offer against the scourge of lung cancer? As a nation, where do we go from here?

The Remarkableness of This Advance in Attacking Lung Cancer

Since 1964, those who have studied public health have been aware of the burden of risk that exists in the American population that has been derived from decades of smoking. Spurred on by the landmark Surgeon General's report of that year,3 the public health community has searched for advances in prevention, screening, or treatment that could reduce the mortality rate from this dreaded disease. In 1988, Dr. Charles Brown and I projected patterns of lung cancer mortality to the year 20254 that have turned out to be largely accurate.5 We were able to make these projections because of the accumulated reservoir of smoking in the population, the strength of the evidence relating smoking to the incidence of lung cancer, and some assumptions regarding trends in quitting and other smoking-related factors. Lung cancer mortality plateaued in the late 1980s among men and around 2004 among women, and both continue to be on the decline.

By far, the most important influence on lung cancer mortality has been a reduction in smoking. The National Cancer Institute-sponsored Cancer Intervention and Surveillance Modeling Network (CISNET) collaborators have estimated the national antismoking campaign has in fact averted hundreds of thousands of deaths.6 Specifically, Moolgavkar et al noted that approximately 70,218 lung cancer deaths were averted in 2000 alone (44,135 among men and 26,083 among women).6 The projections from 25 years ago and the recent modeling efforts have provided context for the work of Ma et al1 and continue to emphasize the importance of public health efforts to further reduce smoking prevalence. Reductions in smoking still require a concerted effort: the 2009 prevalence of smoking among young men and women aged 18 years to 24 years combined was, astoundingly, > 20%, with young men having a rate of 28.0% and young women a rate of 15.6%!7

We must keep in mind the numbers of Americans who will continue to die from smoking, even with the best efforts to implement screening, noting that reducing smoking rates has the potential to avoid the 80% of lung cancer deaths that are not changed by screening and prevent deaths from a range of other harms from heart disease to lip cancer, which screening cannot influence.

This call for attention to smoking should not minimize the potential importance of screening. In many ways, these efforts must go hand-in-hand because the population who has accumulated many pack-years of smoking will indeed benefit from a well-implemented program of secondary prevention (screening). In addition, the limits of screening emphasize the continued need for antismoking efforts (ie, no one should interpret a 20% reduction in mortality as a license to ignore the importance of primary prevention, including clinicians trying to assist patients with smoking cessation as well as public campaigns directed at reducing smoking prevalence).

Why Are These Estimates Important?

It is important to acknowledge the significance of the NLST findings. Lung cancer treatment has been the focus of many hundreds of clinical trials, yet the contribution of advances in treatment have been modest at best, with gains of a few percentage points in relative survival5 reported over the past 20 years, which further emphasizes how remarkable the 20% reduction from screening noted in the NLST is.

These estimates of averted deaths are important because of the debate that will ensue in the near future with the eagerly anticipated full risk-benefit analysis and the cost-effectiveness results from the NLST. Some have attempted to model the cost-effectiveness of screening from published data both with and without NLST results being available and these have led to widely varying estimates of the likely effect of a national screening program.8-10 In large part, these estimates of the cost-effectiveness of lung cancer screening differ because of various assumptions regarding the degree and cost of false-positive results.

False-positive results dominate the picture of screening for many cancers and this is the case with computed tomography (CT) and lung cancer. In the NLST, the rate of adherence to screening was > 90%. The rate of positive screening tests was 24.2% with low-dose CT over all 3 rounds and 96.4% of the positive screening results were false-positive findings.2 Any efforts in the future application of large-scale screening should include awareness of the lessons of the last 40 years of experience with high-volume, low-cost mammography screening in the United States and its contrast with operations in other countries.11,12 Currently, the incentives in the United States with regard to screening remain in the direction of high recall rates, leading to high false-positive results, and therefore it is an inefficient system compared with most European countries that have well-established mammography screening programs. Because of the very high false-positive rates noted in the NLST, it is conceivable that the risk-benefit ratio may not favor the adoption of lung cancer screening. One solution is to work to reduce false-positive results. Although not always the case, this is likely to result in some missed cancers; however, if that is the “price” of having a national screening program, then many more cancers will be found and life-years saved compared with if no program exists at all.

Methods and What Can Be Done Better in the Study by Ma Et Al

Although these estimates are important, the approach taken by Ma et al1 missed some critical elements of population dynamics that may alter what we would really experience with a nationally organized screening program. The estimates in the study by Ma et al are 1-year estimates of the total number of deaths averted and are not expressed in the more common life-years saved approach, which is necessary to appreciate the effect of the screening program over time.1 The likely effect is that Ma et al may have underestimated the total effect over time of a national CT screening program.

In addition, as described by Brown and myself,4 the dynamics of smoking in the population are influenced by age, period, and cohort effects and each must be tied to estimating the long-term effects of a screening program, which is not evident in the article by Ma et al.1 As an example of this, an enormous discrepancy exists between deaths averted for men and women, and that would change over time as the smoking histories of women in the population would “catch up” at least somewhat with those of men.

What Will Happen If Screening Is Implemented?

Several key considerations must be taken into account if screening is implemented in the United States. Who will be included in the eligible population (which was the basis of the lives-saved estimates in Ma et al1)? Will screening be restricted only to those patients who are eligible for the NLST? If there are relaxations with respect to eligibility, will those relaxations be based on age or perhaps on smoking history (and how will smoking history be documented reliably)?

Another critical consideration that has recently emerged as relevant is what to do with those individuals who are diagnosed with early stage lung cancer and then receive presumptively curative treatment, usually surgical resection? As potential lung cancer survivors, what is the appropriate approach to surveillance after treatment? The National Comprehensive Cancer Network has published guidelines13 for surveillance, but to the best of our knowledge there is no significant body of scientific evidence that serves as the foundation for these recommendations. Systematic study of these patients is necessary to ensure that these new patients are provided reasonable guidance as part of their follow-up care.

The 20% Loaf and a Call for National Policy?

Is a 20% reduction in lung cancer mortality and an approximate savings of 12,000 lives per year sufficient justification to implement a national policy for screening? The high rate of false-positive tests and the related workup costs and cost of treating findings that would not benefit patients give pause and thus it is clear why a decision has not been yet taken in this direction.

The next step is for the completed risk-benefits analyses to emerge. If the benefits clearly outweigh the risks and the US Preventive Services Task Force concludes that a recommendation level of A or B is warranted, then the recently upheld Patient Protection and Affordable Care Act calls for the service to be covered by Medicare.14 If the risk-benefit analysis is not so clear, what steps might reasonably be taken to move toward an effective and efficient screening program?

A recently published systematic review of low-dose CT (LDCT) screening concluded that screening adherence is lower in cohort studies compared with the NLST and might be worse with unstructured implementation, resulting in diminished benefits. Given these issues, an LDCT scan performed outside a structured organized process appears to be beyond the current evidence base for LDCT screening for lung cancer.15Haphazard adoption of LDCT outside of organized and clear screening protocols may have potential harms, such as inconsistent follow-up with providers and patients reacting in fear to positive imaging findings, many of which will be false-positive results.

A recent position statement by the International Association for the Study of Lung Cancer recommends demonstration projects to evaluate the implementation of LDCT screening, the establishment of quality metrics, and multiple task forces to address the many critical areas of uncertainty.16

A detailed analysis of the false-positive findings and characteristics of readers with high false-positive rates should be a very high priority. It is important to remember that a cost-effectiveness analysis has 2 components and that if effectiveness is held constant then an important way to improve the cost-effectiveness ratio is to work reduce the “costs” of a screening program, which can include the price of the screening test but more importantly the concerns will be about unnecessary workups and related treatment. As those involved with breast cancer screening worldwide can attest, these can be systematically managed with concerted effort and planning, although not well in the typical entrepreneurial fashion that is currently a part of the US health care system. There are some who might “blame” those who have accumulated 30 pack-years of smoking and believe they may not somehow “deserve” to benefit from screening. That appears to be unfair and short-sighted. Perhaps charges, such as copayments, may be deemed appropriate to partially fund a program and apply some degree of levy to those who have indeed smoked despite nearly 50 years of warnings against this toxic behavior. In any design of an organized screening program, the question of who bears all elements of costs, including current and former smokers; tobacco companies; health insurance companies; and local, state, and federal governments, must be part of the planning effort.

The message of the estimates given in the study by Ma et al,1 as well as the overall context of smoking and lung cancer (and other smoking-related diseases and deaths), compels us to use all of our technologies, primary prevention methods, screening methods, and treatment to the best of our ability as a nation. This is the clear direction in which the results of both the NLST and the study by Ma et al suggest we travel.1,2

FUNDING SUPPORT

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  2. FUNDING SUPPORT
  3. REFERENCES

No specific funding was disclosed.

CONFLICT OF INTEREST DISCLOSURES

The authors made no disclosures.

REFERENCES

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  2. FUNDING SUPPORT
  3. REFERENCES
  • 1
    Ma J, Ward EM, Smith R, Jemal A. Annual number of lung cancer deaths potentially avertable by screening in the United States. Cancer. 2013; 119: 1381-1385.
  • 2
    National Lung Screening Trial Research Team, Aberle DR, Adams AM, et al. Reduced lung-cancer mortality with low-dose computed tomographic screening. N Engl J Med. 2011; 365: 395-409.
  • 3
    US Department of Health, Education, and Welfare. Smoking and Health. Report of the Advisory Committee to the Surgeon General of the Public Health Service. Public Health Service Pub. No. 1103. Washington, DC: Public Health Service. Office of the Surgeon General; 1964.
  • 4
    Brown CC, Kessler LG. Projections of lung cancer mortality in the United States: 1985-2025. J Natl Cancer Inst. 1988; 80: 43-51.
  • 5
    National Cancer Institute. National Cancer Institute Cancer Statistics Review. Trends in Lung Cancer Mortality–Vintage 2009. Bethesda, MD: National Cancer Institute; 2009.
  • 6
    Moolgavkar SH, Holford TR, Levy DT, et al. Impact of reduced tobacco smoking on lung cancer mortality in the United States during 1975-2000. J Natl Cancer Inst. 2012; 104: 541-548.
  • 7
    Centers for Disease Control and Prevention (CDC). Vital signs: current cigarette smoking among adults aged > or = 18 years-United States, 2009. MMWR Morb Mortal Wkly Rep. 2010; 59: 1135-1140.
  • 8
    Goulart BH, Bensink ME, Mummy DG, Ramsey SD. Lung cancer screening with low-dose computed tomography: costs, national expenditures, and cost-effectiveness. J Natl Compr Canc Netw. 2012; 10: 267-275.
  • 9
    McMahon PM, Kong CY, Bouzan C, et al. Cost-effectiveness of computed tomography screening for lung cancer in the United States. J Thorac Oncol. 2011; 6: 1841-1848.
  • 10
    Pyenson BS, Sander MS, Jiang Y, Kahn H, Mulshine JL. An actuarial analysis shows that offering lung cancer screening as an insurance benefit would save lives at relatively low cost. Health Aff (Millwood). 2012; 31: 770-779.
  • 11
    Buist DS, Anderson ML, Haneuse SJ, et al. Influence of annual interpretive volume on screening mammography performance in the United States. Radiology. 2011; 259: 72-84.
  • 12
    Elmore JG, Nakano CY, Koepsell TD, Desnick LM, D'Orsi CJ, Ransohoff DF. International variation in screening mammography interpretations in community-based programs. J Natl Cancer Inst. 2003; 95: 1384-1393.
  • 13
    Wood DE, Eapen GA, Ettinger DS, et al. Lung cancer screening. J Natl Compr Canc Netw. 2012; 10: 240-265.
  • 14
    Patient Protection and Affordable Care Act of 2010. Public Law 111-148 (March 23, 2010), as amended through May 1, 2010. Available at http://www.healthcare.gov/law/full/index.html. Accessed July 5, 2012.
  • 15
    Bach PB, Mirkin JN, Oliver TK, et al. Benefits and harms of CT screening for lung cancer: a systematic review. JAMA. 2012; 307: 2418-2429.
  • 16
    Field JK, Smith RA, Aberle DR, et al; IASLC CT Screening Workshop 2011 Participants. International Association for the Study of Lung Cancer Computed Tomography Screening Workshop 2011 report. J Thorac Oncol. 2012; 7: 10-19.