The rationale for, and design of, a lung cancer screening program
ABSTRACTWe are entering a new era in which lung cancer screening may be considered the standard of care. The National Lung Screening Trial (NLST) has shown that the number of deaths due to lung cancer can be reduced through screening with low-dose computed tomography (CT) in a high-risk population (N Engl J Med 2011; 365:395–409). Key issues—such as how to manage lung nodules, how to improve cost-effectiveness, and how to minimize radiation exposure—need to be addressed when designing a lung cancer screening program. Time and further technical advances will help to optimize the programs that are developed.
KEY POINTS
- The NLST documented a 20% reduction in the rate of death from lung cancer with low-dose CT screening compared with chest radiography screening (number needed to treat = 320). This was in a population at high risk (age 55–74 with a smoking history of at least 30 pack-years, at least some of it within the past 15 years).
- CT screening detects many lung nodules, of which only a few (3.6% in the NLST) prove to be cancer.
- In view of the positive results of the NLST, Cleveland Clinic has begun a lung cancer screening program, using the same entry criteria as those in the NLST.
- Of possibly greater impact than detecting lung cancer will be the opportunity to promote smoking cessation.
WE SET OUT TO DESIGN A SCREENING PROGRAM
With the evidence supporting a reduction in the rate of lung cancer mortality, and knowing the remaining challenges, we set out to provide a lung cancer screening program within Cleveland Clinic. In the design of our program, we considered several questions, outlined below.
Who should be offered low-dose CT screening?
The results of the NLST led to a great deal of excitement about lung cancer screening in both the medical community and the general public. The positive side of this publicity is that lung cancer is receiving attention that may lead to support for further advances. The negative side is that many patients who may seek out lung cancer screening are not at high enough risk of lung cancer to clearly benefit from it.
In the NLST, a very high-risk cohort was studied, as defined by clinical variables (age 55 to 74, at least 30 pack-years of smoking, and if a former smoker, had quit within the past 15 years). In this high-risk group, 320 patients needed to be screened (with three yearly chest CT scans) for one life to be saved from lung cancer, and only 3.6% of all lung nodules found (4 mm or larger) were actually lung cancer. In a group at lower risk, the number that needed to be screened to save one life would be higher, and the percentage of lung nodules that truly were lung cancer would be lower. This would lead to higher risks and costs related to screening, without a proven benefit to members of the lower-risk group.
The risk of the NLST cohort developing lung cancer was approximately 0.6% per year. Lung cancer risk-prediction models have been developed and published. Up to 2011, the three most commonly used models had only moderate accuracy at predicting risk.22–25 In 2011 a risk model based on the PLCO cohort was developed and published.26 This model seemed to be more accurate but perhaps a bit harder to apply in practice.
We discussed whether using a validated risk predictor with a target of 0.6% per year (ie, the risk in the NLST trial) would be an adequate means of deciding on candidacy for lung cancer screening or if we should strictly adhere to the inclusion criteria of the NLST cohort. We feel that the NLST cohort is the only group with true evidence of benefit (a reduction in the lung cancer-specific mortality rate). Thus, for our program’s entry criteria, we decided to use the same clinical predictors used for entry in the NLST.
How will the right patients get scheduled for low-dose screening CT?
Patients who enter the lung cancer screening program from our health system will require a physician’s order.
We are fortunate to have an electronic medical record in place. We have created an order set within the electronic record for low-dose chest CT. The order will eventually be able to be entered as “CT lung screening w/o” (ie, without contrast).
For patients from outside of our health system who would like to enter the lung cancer screening program, the entry criteria will be the same (see above). We will ask for the name of the patient’s primary care practitioner. If the patient does not have one, a member of our Respiratory Institute will see and enroll the patient.
How often should patients be screened, and for how many years?
Unfortunately, questions about the frequency of screening and how many years it should continue remain unanswered.
In the NLST, a similar number of early-stage lung cancers were detected during each of the three screening rounds. In both the NLST and PLCO trials, differences in the mortality rate curves began to narrow during the observation period, when active screening was no longer occurring. Thus, it is possible that a longer duration of screening could lead to a further reduction in mortality rates. Others have questioned whether a similar benefit, with less cost and risk, could be obtained by screening every 2 years.
The large amount of data obtained from the NLST and other CT-based studies is being reviewed so that models can be developed to help answer these questions. For now, we suggest at least three yearly CT screenings, with the hope that we will have clearer answers to these questions over time.
How will low-dose CT be performed and interpreted?
The parameters for low-dose CT were very tightly controlled and monitored during the NLST. This quality-control effort, designed to improve consistency across sites and to minimize risk to patients, should be carried into lung cancer screening programs.
Our program will closely mimic the CT performance criteria used in the NLST (tube current-time product 40 mAs for all patients, field of view lungs only, lung kernel images 3 mm at 1.5-mm intervals, and soft-tissue kernel images 5 mm at 2.5-mm intervals).27 In the initial phase of the program, all screening scans will be performed at Cleveland Clinic’s main imaging facility.
Small lung nodules remain quite challenging to detect and measure. To minimize variability in scan interpretation, the NLST readers were all expertly trained radiologists. Despite this, much variability was noted in the number of nodules detected, their measured size, and the follow-up recommendations. All of the screening CT images for our program will be interpreted by board-certified radiologists with expertise in chest imaging.
Other screening studies have included novel imaging assessment in their testing algorithms, particularly volumetric analysis of lung nodules.28 These tools may prove to assist in nodule detection, measurement, and management over time. At this point, we do not think they have been studied and standardized enough to include them in a standard-of-care screening program. We hope that they will evolve to the point of clinical utility in the near future.
Lung cancer screening is not currently covered by most insurers, including Medicare, although one major insurer has recently started to cover it. We expect decisions on coverage from other insurers in the next 12 months. In the meantime, we offer a low-dose screening chest CT to our patients for $125, which includes the radiologist’s fee for interpreting the scan.
Smoking cessation
The NLST showed that low-dose CT screening can reduce lung cancer mortality rates by 20% in a high-risk group. A 50-year-old active smoker who quits smoking reduces his or her risk of dying of lung cancer by more than 50%.29 Entry into a lung cancer screening program provides an opportunity for education and assistance with tobacco dependency.
At Cleveland Clinic, we have an active Tobacco Treatment Center within our Wellness Institute. All lung cancer screening participants who are identified as active smokers will be given a program brochure and will be offered a consult in the program.
