Download The International Association Study Lung Cancer (IASLC) Strategic

Commentary
The International Association Study Lung Cancer (IASLC)
Strategic Screening Advisory Committee (SSAC) Response
to the USPSTF Recommendations
John K. Field, PhD, FRCPath,* Denise R. Aberle, MD,† Nasser Altorki, MD,‡
David R. Baldwin, MD, FRCP,§ Carolyn Dresler, MD, MPA,║ Stephen W. Duffy, MSc,¶
Peter Goldstraw, FRCS,# Fred R. Hirsch, MD, PhD,** Jesper Holst Pedersen, DMsci,††
Harry J. de Koning, MD, PhD,‡‡ James L. Mulshine, MD,§§ Daniel C. Sullivan, MD,║║
Ming-Sound Tsao, MD, FRCPC,¶¶ and William D. Travis, MD## on behalf of the International
Association for the Study of Lung Cancer Strategic Screening Advisory Committee.
(J Thorac Oncol. 2014;9: 141–143)
T
he International Association for the Study of Lung Cancer
(IASLC) Strategic Screening Advisory Committee
(SSAC) has prepared the following response to the United
States Preventive Services Task Force (USPSTF) draft recommendation on computed tomography (CT) screening [http://
www.uspreventiveservicestaskforce.org/uspstf13/lungcan/
lungcandraftrec.htm] with the associated systemic review.1
The Cancer Care Ontario Programme in Evidence-Based
Care (CCOP)2 has also undertaken a similar systemic review.
The IASLC SSAC was set up during the World Lung Cancer
Conference 2011.3
*Department of Molecular and Clinical Cancer Medicine, Institute of
Translational medicine, The University of Liverpool Cancer Research
Centre, Liverpool, United Kingdom; †Department of Radiology, David
Geffen School of Medicine at UCLA, Los Angeles, California; ‡Division
of Thoracic Surgery , New York Presbyterian-Weill, Cornell, New York,
New York; §Respiratory Medicine Unit, Nottingham University Hospitals,
Nottingham, United Kingdom; ║Rockville, Maryland;¶Wolfson Institute
of Preventive Medicine, Queen Mary University of London, London,
United Kingdom; #National Heart and Lung Institute, Imperial College,
London, United Kingdom; **University of Colorado, Cancer Center,
Denver, Colorado; ††Department of Cardiothoracic Surgery, University
of Copenhagen,
Copenhagen, Denmark; ‡‡Department of Public
Health, Erasmus MC, Rotterdam, The Netherlands; §§Rush University,
Chicago, Illinois; ║║Department of Radiology, Duke University, Medical
Center, Durham, North Carolina; ¶¶Princess Margaret Cancer Centre and
University of Toronto, Toronto, Canada; and ##Department of Pathology,
Memorial Sloan Kettering Cancer Center, New York, New York.
Disclosure: The authors declare no conflict of interest.
Address for correspondence: John K. Field, PhD, FRCPath, The University
of Liverpool Cancer Research Centre, Department of Molecular and
Clinical Cancer Medicine, Institute of Translational Medicine, Roy Castle
Building, 200 London Rd, Liverpool, L3 9TA, United Kingdom. E-mail:
[email protected]
Copyright © 2013 by the International Association for the Study of Lung
Cancer
ISSN: 1556-0864/14/0902-0141
Lung cancer remains the most lethal cancer across the
world. Almost 90% of those cancers are thought to be the
consequence of prolonged exposure to tobacco-combustion
products. The USPSTF recent draft recommendations of the
statement on lung cancer screening, recommended the use
of low-dose CT (LDCT) screening in certain populations of
current and former smokers, which were otherwise healthy,
as a cancer-screening approach. This recommendation was
buttressed by a large body of information, but most significant was the large, randomized National Lung Screening Trial
(NLST),4 which reported a reduction in tobacco-related lung
cancer mortality of 20% after 6 years of follow-up after a
baseline and two annual follow-up rounds of CT screening.
IMPLICATIONS OF THE IMPLEMENTATION OF
CT SCREENING IN THE UNITED STATES
The USPSTF draft recommendation is a welcome endorsement of LDCT screening to combat a devastating disease. The
recommendation considered the effectiveness of CT screening in
reducing mortality, the performance characteristics of CT screening, the effectiveness of surgical resection in early-stage disease,
and the harms of both screening and surgical resection. However,
these recommendations go beyond a restatement of reduced lung
cancer mortality in high-risk individuals; they challenge the U.S.
health care system to continue to improve the CT screening process as implementation begins. Several unanswered questions
that will determine the ultimate success of implementation are
proffered. These include the appropriate risk groups to consider,
the effects of screening in different demographic subgroups,
cost effectiveness, the modeling of radiation effects, methods
to improve the discrimination between benign and malignant
nodules, the incorporation of biological markers, the integration
of intensive tobacco cessation for persistent users, and the psychological consequences of screening on health behaviors and in
clinical practice. The Task Force encourages screening in highrisk individuals while concurrently appealing to the medical
work force to better delineate the benefits to risks of lung cancer
screening. This will require that U.S. screening centers commit to
Journal of Thoracic Oncology ® • Volume 9, Number 2, February 2014
141
Field et al.
Journal of Thoracic Oncology ® • Volume 9, Number 2, February 2014
collecting the necessary demographic, clinical, imaging, tobacco
cessation, and outcomes data to inform these unanswered questions in the process of screening implementation.
IASLC Statement
The IASLC has previously supported research into CT
screening trials in the light of the public health burden of lung
cancer. Each national health service now has an opportunity to
decide its own way forward regarding the merits of CT screening based on their interpretation of the existing NLST data and
information from other lung cancer screening trials. However,
the IASLC makes the following statements: First, the implementation of any screening process should be performed incorporating best practice for screening care in centers that are able
to achieve excellence in providing this service and that have a
multidisciplinary group of experts focused on this problem. In
discussions about screening, for those who have not done so,
smoking cessation is the most important measure available to
improving overall health outcomes. For former smokers considering lung cancer screening, it is clear that the increased risk
of developing lung cancer is diminishing but lifelong.5
The IASLC SSAC recommends that the following current issues should be considered by national health service providers as they consider implementing lung cancer screening:
Fitness Criteria and Upper Age Limit
Cost Effectiveness
The cost of providing lung cancer screening is related to the
process of screening delivery. Preliminary modeling studies in
the United States have shown that providing lung cancer screening according to best available practice could be delivered cost
effectively.6 Valid cost-effectiveness data will ultimately drive the
success of implementation in many countries, balancing the incremental toll that lung cancer screening will exact on health care
systems with improved health outcomes. We await cost effectiveness data from the NLST and Nederlands-Leuvens Longkanker
Screenings Onderzoek (NELSON) trial data. Moreover, the cost
effectiveness of lung cancer screening can be further improved by
the addition of smoking cessation counseling.7
Radiological Protocol for CT Screened Nodules
Size quantification on serial CT scans for lung cancer
screening is helpful in evaluating whether a pulmonary nodule
is benign or malignant. Evaluation of suspicious lung nodules
involving the use of quantitative CT imaging, which allows discrimination of rapidly growing nodules that may be cancer from
slower growing nodules that are not likely to evolve into cancer, is
a developing field and the way forward. Many investigators have
suggested that quantifying whole nodule volume could solve
some of the limitations of diameter measures8,9 and many studies
have explored the value of volumetry.10–13 The rigorous applications of volume measurement guidelines will most likely lead to
more accurate management of the lung cancer screening process.
Selection Criteria for CT Lung Cancer
Screening Programs in the United States
The NLST eligibility criteria were based largely on age
(55–74 years) and heavy-smoking history (≥30 pack-years)
142
among current and former smokers (<15 years since quitting). However, as indicated in the USPSTF document, future
research should include identifying methods for focusing
LDCT screening on persons at higher risk for disease, to
improve test sensitivity, specificity, and cost-effectiveness.
Several risk-prediction models have recently been described to
better define the optimal risk cohort,14–17 including the model
developed using the Prostate, Lung, Colorectal and Ovarian
Cancer Screening Trial data.15 This model improved the sensitivity of LDCT relative to the NLST selection criteria (83.0%
versus 71.1%, p<0.001) and its positive predictive value (4.0%
versus 3.4%, p=0.01) without loss of specificity or decrease in
mortality reduction. Furthermore, a more recent analysis of the
NLST data reported that the prevention of lung cancer deaths
in the LDCT screening arm as compared with that in the radiography arm increased according to risk quintiles, with 60% of
participants at the highest-risk quintiles 3 to 5 accounting for
88% of the screen-prevented lung cancer deaths, whereas 20%
of participants at lowest-risk quintile 1, accounting for only 1%
of lung cancer deaths.18 These results suggest that the application of risk-prediction models could reduce the number of
individuals that need to be screened to prevent one lung cancer
death, reduce false-positive rates of screening, and improve the
overall cost-effectiveness of lung cancer screening.
The imposition of any arbitrary upper age limit in selecting patients for inclusion in a LDCT screening program is certain to be challenged by patients and their advocacy groups.
The use of age is a discredited and inaccurate surrogate for an
assessment of “fitness” or comorbidity. In addition, any upper
age limit, such as that of 79 years proposed by the USPSTF,
will be revised as we better define the demography of the most
appropriate screening cohorts (http://www.uspreventiveservicestaskforce.org/uspstf13/lungcan/lungcandraftrec.htm).
However, it is reasonable to assess fitness before entry to
a screening program and at key intervals thereafter to ensure
that (1) screenees are able to undergo, with tolerable risks, both
the investigations indicated to evaluate suspicious nodules and
the subsequent treatment of suspicious nodules or proven lung
cancers, and (2) their life expectancy because of comorbid
disease(s) will not prematurely limit their life expectancy relative to the treatment of a documented lung cancer.
Lung Cancer CT Screening—Considerations
of Benefits and Harms
The NLST has shown clearly that LDCT benefits patients
by reducing lung cancer mortality and that this also reduces
all-cause mortality. Harms may result from physical and psychological sources in the context of discovery of nodules, their
workup, and overdiagnosis. The latter is especially important,
as all these harms that apply to life-limiting cancer apply to
overdiagnosed cancer with none of the benefits, except smoking cessation. It is important to take into account the influence
of comorbid conditions as NLST showed that individuals with
multiple comorbid conditions did not benefit from CT screening.18 This effect can be reduced through careful fitness assessment as outlined above. Harms can also be reduced by the
Copyright © 2013 by the International Association for the Study of Lung Cancer
Journal of Thoracic Oncology ® • Volume 9, Number 2, February 2014
method of workup of nodules. NELSON has shown that the
frequency of invasive procedures can be minimized by a protocol to assess growth using CT volumetry at 3- and 12-month
intervals depending on the size of the nodule detected.19
With modern radiological techniques, radiation dose is
low, and likely to be even lower in the future. However, it is
important to ensure adherence to low-dose protocols by ensuring that those managing screening programs are well versed
in contemporary CT dose-reduction techniques as well as the
selective use of further diagnostic imaging.
CCOP Guidelines on Lung Cancer Screening
The CCOP have also undertaken an in-depth system of
review of the screening trials and formulated their guidelines.2
In essence, many similarities with the USPSTF, except they
have remained with the NLST selection criteria based on smoking history and age 55 to 74 years. The working group endorsed
the NLST criteria, however, it did emphasize that patient acceptability, cost effectiveness, feasibility, and systems capacity
would in time indicate whether these parameters were reasonable. The group also recommended that high-risk individuals
should be screened for 2 consecutive years and then once every
2 years after a negative scan, based on evidence from the Multicentric Italian Lung Detection Trial (MILD) trial, which did not
demonstrate a shift to higher-stage disease with biennial screening compared with annual screening.20 They make a particular
point that opportunistic screening should not take place and that
screening should only be undertaken in centers of excellence.
Planned Recommendations from IASLC SSAC
The IASLC SSAC hosted the second CT Screening before
the World Conference on lung cancer in Sydney 26-27 October
2013, where all of these issues were considered fully and recommendations will be provided for the international membership.
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