Implementation of a Lung Cancer-Screening Program

Douglas Arenberg The National Lung Screening Trial (NLST) demonstrated that lung cancer screening with three annual low-dose CT scans has the potential to reduce lung cancerspecific mortality by 20 % among a population of older heavy smokers. Many questions should be raised to convert this efficacy into effective clinical practice. Screening for lung cancer will be most effective if it is conducted solely for high-risk individuals that can benefit from cancer treatment. Ongoing screening should be accompanied by continued research into risk modeling, communication strategies, and biomarkers. For clinicians establishing lung cancer screening programs, this should be done responsibly, adhering to practices specified in the design of the NLST, and with careful attention given to proper management of screen-detected abnormalities and maintenance of screening registries. - Early detection, while necessary, is insufficient to establish the efficacy of a test intended to screen for cancer. Only reduction of disease-specific mortality among a screened population can indicate efficacy. Clinical researchers with an interest in lung cancer have pursued an effective screening test for over 50 years. The National Lung Cancer Screening Trial (NLST) answered this call, randomizing 50,000 individuals at risk of lung cancer to either low-dose helical CT or CXR annually for three years. The results showed that LDCT screening reduced lung cancer-specific mortality among heavy (30 pack-years or more) current or former (within 15 years) smokers between the ages of 55 and 75 from 309 to 247 deaths per 100,000 person years (relative risk 0.8) [1]. Since then, after announcements about the cost effectiveness of screening for lung cancer with LDCT, the USPSTF has issued draft recommendations for annual LDCT for heavy current or former smokers age 5579 (http://www. uspreventiveservicestaskforce.org/draftrec.htm). Cautious editorial writers have correctly pointed out the perils of indiscriminately offering screening on a widespread basis. These hazards are numerous, and some are potentially insidious. Even before these preliminary announcements, many centers began to offer screening with LDCT. The objective of any screening program should, first and foremost, be to minimize harm when screening an asymptomatic population. NLST results allude to the potential benefits of screening, but converting a clinical trial into clinical practice is the challenge. This review will attempt to outline the elements of that process. Converting Efficacy into Effectiveness The results of the NLST were robust, causing great excitement for the lung cancer community. But clinical trial efficacy cannot automatically be converted into real-world effectiveness. When trying to generalize the findings of a clinical trial, it is necessary to examine the details of the study, and ask: Do the patients in the study resemble the patients in your examination room? The NLST investigators anticipated this question and compared participants in the NLST with the population of eligible smokers in the US using data from the US census tobacco supplement. They found that screen-eligible subjects in the US population were less educated, slightly older, and more likely to be current smokers than the NLST study subjects [2]. Although each of these differences was small, one cannot ignore the potential effect they would have on real-world efficacy of LDCT screening. Other important questions include: Did the setting of the study have any effect on the outcome of the study? If so, do the qualities of the study setting match your practice setting? For example, screening programs must recognize the need for quality control of the specifications of CT imaging, the qualifications and expertise of the interpreting radiologists, and the standardized criteria for reporting abnormalities. Each of these factors was prospectively determined and closely monitored in the conduct of the NLST [3], and the effect of these behind the scenes quality-control measures on the effectiveness and safety of LDCT screening should not be taken for granted. Furthermore, although evaluation of abnormal screening findings was not standardized in the NLST, all findings were generally followed up in centers where there is significant expertise in the management of incidental or screen-detected nodules. It is a mistake to look at the data on screening in isolation from the setting in which these reductions in mortality were achieved. Anyone starting a lung cancer screening program should understand both the risks and benefits of screening, including the incidence of false-positive results and appropriate diagnostic pathways. Most nodules discovered on LDCT are benign, and the process should focus on obtaining proof that the nodule is benign with the least amount of cost and risk to the patient. In almost all instances this means careful reassurance of anxious patients, and serial follow up at interva (...truncated)