Lung cancer screening: Examining the issues
ABSTRACTThe goal of screening is to detect disease at a stage when cure or control is possible, thereby decreasing disease-specific deaths in the population. Many studies have attempted to demonstrate that lung cancer screening using chest radiography or computed tomography (CT) identifies patients with lung cancer and reduces cancer-related mortality. Until recently, there was no evidence confirming a reduction in disease-specific mortality with screening. Early cancer screening should result in a gradual population-wide stage shift toward earlier cancer stages over time, but stage shifting was not reported in early lung cancer screening studies. Lead-time, length-time, and overdiagnosis biases may each have an impact on screening studies reporting survival as an outcome. In this past year, the National Lung Screening Trial reported a significant reduction in cancer-related mortality as a result of screening with chest CT imaging. This will shape the direction of future screening programs.
IS SCREENING COST-EFFECTIVE?
It is difficult to calculate the cost-effectiveness of CT screening because the impact of screening on mortality and the economic implications of false-positive findings are not well understood. A cost-effectiveness analysis of helical CT screening assumed that screening would result in a 50% stage shift and a 13% reduction in mortality.34 Under these assumptions, the cost-effectiveness was greater among current smokers ($116,300 per quality-adjusted life year saved by screening) than among currently quitting smokers ($558,600) or former smokers ($2,322,700). These investigators concluded that lung cancer screening is unlikely to be cost-effective, especially among those with the lowest levels of current tobacco exposure (quitting or former smokers).
Larger stage shifts or reductions in mortality would be expected to translate into greater cost-effectiveness, although the real-world effects of screening on these parameters are uncertain. Data from a US nationwide survey suggested that only about one-half of all current smokers would opt for surgery following a positive screening result, which might significantly decrease the cost-effectiveness of treatment.35
It is unclear how well the methods used in screening studies such as the NLST would translate to actual clinical practice at a national level, or how the health care system would manage the many small lung nodules that would be identified using this approach.
HOW WILL FUTURE DEVELOPMENTS AFFECT LUNG CANCER SCREENING?
Ongoing studies will continue to refine our understanding of the impact of lung cancer screening. For example, the randomized Prostate, Lung, Colorectal, and Ovarian Screening Trial is examining chest radiograph screening versus control in both smokers and never-smokers between 55 and 74 years of age.36 It is anticipated that this study will provide important information about how well chest radiographs perform for the identification of lung cancer in high- and lower-risk populations. Large randomized trials in Europe are comparing CT with no imaging for lung cancer screening.37 Efforts to better characterize specific patient populations who are at the greatest risk of lung cancer may help to improve the efficiency and cost-effectiveness of screening. Advances in molecular testing may help to identify molecular and genetic tumor biomarkers that herald increased lung cancer risk and greater need for screening. More research is needed to better understand the optimal management of patients with small lung nodules on screening tests. Professional societies are poised to publish revised screening recommendations as data from the NLST become available. Finally, insurers will need to evaluate the evidence and develop reimbursement policies.
SUMMARY AND CONCLUSIONS
Lung cancer screening efforts conducted over the last several decades have shown that it is possible to identify early lung cancer in high-risk patient populations. However, demonstrating a clear improvement in cancer-related mortality has been more difficult. Biases inherent to noncontrolled trials of screening may explain some of the beneficial effects on survival observed in some studies. Recent results from the NLST have for the first time demonstrated a significant reduction in lung cancer mortality in high-risk patients screened for lung cancer with chest CT, although there are continuing concerns about the cost of screening, the risks from radiation exposure, and the additional testing resulting from the identification of small benign lung nodules. Ongoing research will help to maximize the benefit of lung cancer screening and minimize the related risks.
