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.
What do we identify as a lung nodule, and how should they be managed?
Studies of CT-based screening have highlighted the tremendous number of lung nodules that are identified and the low likelihood of malignancy in those that are less than 1 cm in diameter. Many screening studies define a positive result as a lung nodule above a particular size. The NLST used 4 mm or greater as the cutoff. The lower the cutoff, the greater the number of nodules found, and the lower the overall likelihood of malignancy in the nodules.
Studies in which annual CT screening was the intervention are able to use size criteria in part because the study design ensures another CT will be performed 12 months later. Current nodule management guidelines suggest 12-month CT follow-up of incidentally discovered lung nodules, 4 mm or smaller, in at-risk patients.30 In a screening program, particularly one for which the patient must pay, the 12-month screening CT cannot be guaranteed. This makes it more difficult to ignore the smallest nodules identified on CT screening. Given this, we will be reporting all lung nodules identified, regardless of size on the initial screening.
Most studies of CT screening have reported any new nodule identified in subsequent screening rounds regardless of size. Though it is intuitive that a new nodule would have a high likelihood of malignancy in a high-risk cohort, malignancy rates have been reported to be as low as 1% for new nodules. As with the initial round of screening, we will report all new lung nodules identified in subsequent screening rounds.
The recommendations for the evaluation of lung nodules, both within the report and at the lung nodule clinic, are in keeping with currently available guidelines, such as those from the Fleischner Society30 and the American College of Chest Physicians.31 For incidentally discovered lung nodules in patients at high risk, the Fleischner Society recommendations are as follows30:
- For nodules 4 mm or smaller, follow-up in 12 months; if no growth, then no further follow-up
- For nodules 4 to 6 mm, follow-up at 6 to 12 months, then 18 to 24 months if no growth
- For nodules 6 to 8 mm, follow-up at 3 to 6 months, then 9 to 12 months, then 24 months if no growth
- For nodules 8 mm or larger, follow-up at 3, 9, and 24 months, or positron emission tomography, or biopsy, or both.
If the nodule is large enough or is deemed to be of high enough risk, adjuvant testing with diagnostic imaging, guided bronchoscopy, transthoracic needle aspiration, or minimally invasive resection will be offered. All patients with nodules believed to require biopsy will be discussed at our multidisciplinary lung cancer tumor board before biopsy.
How do we make practitioners and patients aware of the program and its indications, risks, and benefits?
Education will be the key to having lung cancer screening adopted as the standard of care, to lung cancer screening being provided within a well-designed and capable system, and to ensuring that patients have realistic expectations about screening. Articles such as this and grand rounds presentations within our health system will help provide education to our colleagues. Broader marketing campaigns will be considered in the future once demand and system capabilities are clearly identified. A patient information brochure will be provided at the time of the screening test (see the patient information sheet that accompanies this article).
How do we help to advance best practice?
As excited as we are that low-dose CT-based lung cancer screening has been proven to reduce lung cancer mortality rates, it is clear that there is a lot of room to improve the programs that are developed based on current data.
Advances in our ability to accurately predict an individual’s risk of developing lung cancer will allow us to offer screening to those it is most likely to benefit.
Advances in smoking cessation and chemoprevention will help to minimize the number of lung cancers that develop.
Advances in our ability to determine the nature of lung nodules will allow us to accelerate treatment of very early lung cancer while minimizing additional testing on benign nodules; advances in our ability to treat localized and advanced disease will improve the outcome for those identified as having lung cancer.
To help move the science of screening forward, we will develop a screening program registry that can be populated from the order set and the templated report. The registry can be used to ensure appropriate patient care, while studying relevant epidemiologic, quality, and cost-related questions.
We hope to assess novel imaging software capable of assisting with the detection and characterization of lung nodules.
We have an active biomarker development program to assess the ability of breath and blood-based biomarkers to identify those at risk of developing lung cancer; to assist with the management of screening-detected lung nodules; to assist with the diagnosis of early stage lung cancer; and to characterize the nature of the cancers identified. Accurate biomarkers could lead to further decreases in mortality rates while reducing the risks and costs of a screening program.
We have strong surgical, medical, and radiation oncology programs, actively pursuing advances in minimally invasive resection procedures and ablative and targeted therapies.
ENTERING A NEW ERA
We are entering a new era of lung cancer screening. The NLST has shown that lung cancer morality rates can be reduced through low-dose CT screening in a high-risk population. Many challenges remain, such as managing the nodules that are discovered, determining if the program is cost-effective, and minimizing radiation exposure. These need to be considered when designing a lung cancer screening program. Advances over time will help us optimize the programs that are developed.
