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Screening for Lung Cancer: Challenges for the Thoracic Surgeon
Lung cancer is a global health burden and is among the most common and deadliest of all malignancies worldwide. In the United States, lung cancer accounts for more than 25% of all cancer deaths, exceeding deaths from breast, colon, and prostate cancers combined. More than 80% of individuals with lung cancer die of the disease, primarily because a large proportion of patients with lung cancer present with locally advanced or metastatic disease. Intuitively, early detection of resectable and potentially curable disease could reduce the overall death rate from lung cancer. Historically, screening for lung cancer was not recommended by the majority of clinical societies and health care agencies in the United States. However, following the mortality benefit identified in the National Lung Screening Trial (NLST) in 2011, most U.S. guidelines now recommend screening with low-dose computed tomography (LDCT) in at-risk populations. This shift in policy can be expected to increase significantly the number of patients found to have lung cancer, but also those found to have benign lung nodules. Much of the current debate has turned toward identifying the most appropriate “at-risk” populations for screening, ensuring appropriate management of screen detected nodules, and defining the optimum duration of CT screening. This chapter briefly discusses the history of and rationale for lung cancer screening and addresses optimization of screening protocols.
History of Lung Cancer Screening
Chest Radiograph Screening
Interest in screening high-risk patients for lung cancer was sparked when the association between cigarette smoking and lung cancer was first appreciated by Doll and Hill in the 1950s. The first mass screening project was conducted by Brett in London from 1960 to 1964. Although not a randomized trial, 55,034 men were assigned to undergo either chest radiography (CXR) every 6 months for three years (the screened group) or a single CXR at the beginning of the study, followed by a repeat CXR at the end of the 3-year period (the “unscreened” group). At the end of the 3-year period, more lung cancers were detected in the screened group compared to the unscreened group (132 vs. 96 cases). In addition, resectability was enhanced in the screened group. Despite these findings, lung cancer–specific mortality was not different between the two groups.
In the 1970s, the National Cancer Institute funded three randomized trials for lung cancer screening using both CXR and sputum cytology at Johns Hopkins, Memorial Sloan-Kettering Cancer Center, and the Mayo Clinic. Again, more cancers were found in the screened groups of patients, and resectability rates were significantly higher in the screened group. Nonetheless, again there was no statistically significant difference in the lung cancer–specific mortality between the screened and unscreened populations in any of the trials.
Early Computed Tomography Screening Studies
In the 1990s, increased resolution and data-acquisition speeds of modern computed tomographic (CT) scanners rekindled interest in screening for lung cancer. Initial findings from Henschke and colleagues of the Early Lung Cancer Action Project (ELCAP) showed that in a high-risk population, LDCT was superior to CXR in detection of lung nodules. Notably, 2.7% of those enrolled in the CT screening program had lung cancer, the great majority of which were stage I. A subsequent report by the I-ELCAP group addressed overall curability estimated through 10-year survival rates of patients found to have stage I lung cancer by CT screening. The authors reported an estimated 88% 10-year survival rate, markedly higher than survival rates predicted by the current staging system or among those presenting as a result of symptoms. They inferred that because CT screening leads to early detection of lung cancer and because those lung cancers found as a result of CT screening are curable, that CT screening leads to a reduction in lung cancer mortality. Several other groups subsequently evaluated CT screening for lung cancer. A review by Black and colleagues published in 2007 identified 12 studies, including two randomized and 10 single-arm observational studies. Significant variability existed in the study populations and in the definition of a positive finding in each. The percentage of positive screenings ranged from 5.1% to 51%. From baseline screenings, 1.8% to 18% of positive findings led to a diagnosis of cancer. The majority of the tumors were stage I (53% to 100%), with a high resectability rate (>78%). Only one of the studies reported 5-year survival: 76% for patients with cancer detected at baseline screening and 65% for patients with cancer detected at annual repeat scanning.
Screening for lung cancer with LDCT was not universally embraced, however. Bach and colleagues reported the findings from CT screening of 3246 high-risk patients from multiple institutions. The authors reported a threefold increase in individuals diagnosed with lung cancer and a tenfold increase in patients undergoing lung resection (compared to expected cases). They also found no evidence of a decline in the number of patients with advanced stages of disease or of deaths from lung cancer in the screened groups. The authors concluded that CT screening might not meaningfully reduce the risk of dying from lung cancer and suggested that CT screening is inherently prone to overdiagnosis, thus exposing patients to unnecessary surgery. The study generated controversy given that the follow-up was relatively short (3.9 years) and that at least one of the three studies did not require the exclusion of symptomatic individuals, possibly undermining the core concept of screening.
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