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Department of Radiology, The Mount Sinai Medical Center, New York, New York
* Address correspondence to Dr Wilck, The Mount Sinai Medical Center, Department of Radiology, Box 1234, One Gustave L. Levy Pl, New York, NY 10029-6574 (Email: eric.wilck{at}mssm.edu).
Presented at the Minimally Invasive Thoracic Surgery Summit, New York, NY, June 8–9, 2007.
Lung cancer is the leading cause of cancer deaths in both men and women. In 2007, more than 200,000 new cases will be diagnosed in the United States. More individuals die of lung cancer than of colon, breast, and prostate cancer combined. In general, a lung cancer diagnosis imparts a poor prognosis, with 60% of patients dying within 1 year of diagnosis. Surgical resection of an early lung cancer, on the other hand, has a favorable prognosis. After resection of a stage 1A bronchogenic carcinoma, the patient has a 5-year survival of about 80% to 90%. With these thoughts in mind, large screening trials to detect early lung cancer have been undertaken.
The goal of a screening computed tomography (CT) of the chest is to detect a solitary pulmonary nodule in a patient at risk for lung cancer. Risk factors include smoking, environmental exposure, prior radiation, or family history. The risk of malignancy of a solitary pulmonary nodule also increases with age. Solitary pulmonary nodules are fairly common, and the incidence of malignancy depends upon the population under study.
The definition of a solitary pulmonary nodule is a relatively spherical opacity, 3 cm or less in diameter, surrounded by lung parenchyma. There should be no associated atelectasis or hilar lymphadenopathy. The probability of malignancy of a solitary lesion depends on both the appearance of the nodule and the clinical risk.
When a solitary pulmonary nodule is evaluated, there are certain features that favor a benign (Table 1) vs malignant cause (Table 2). Also, certain features of nodules correlate with the likelihood of malignancy, cell type, and growth rate (Table 3). Small ground-glass nodules that are malignant tend to grow very slowly compared with solid cancers that grow more rapidly [1].
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The second study, "Computed Tomography Screening and Lung Cancer Outcomes," was published in The Journal of the American Medical Association on March 7, 2007 [3]. This study by Peter Bach and colleagues enrolled 3246 asymptomatic current or former smokers for annual CT scans and had a median follow-up of 3.9 years. Results were compared with those expected in high-risk populations on the basis of validated prediction models. A total of 144 lung cancers were diagnosed, 44.5 of which were expected based on prediction models. There were 109 lung resections, which was 10 times the expected number, 42 advanced cancers (33.4 expected), and 38 deaths (38.8 expected). This study concluded that screening for lung cancer with low-dose CT may increase the rate of lung cancer diagnosis and treatment but may not meaningfully reduce the risk of advanced lung cancer or death from lung cancer. Critics of this study indicate that prolonged survival does not equal reduced mortality [4]. The current general consensus is that asymptomatic individuals should not be screened outside of clinical research studies.
Confusion arises in the medical community when two similar studies apparently yield disparate results. Can these studies be reconciled if one assumes they are both valid? Several possible explanations have been considered to account for these discordant results, including differences in the screened populations, accuracy of the prediction model used, differences in the outcome measures of mortality vs survival, and the possibility of chance [4]. One possible explanation is that lung cancer is a heterogeneous group of malignancies that have varying biologic behaviors and cannot be treated as a single entity [5]. Some lung cancers will progress in a predictable fashion over time through advancing stages. Early resection of these cancers will prevent progression of disease and result in a high estimated survival rate as predicted by the International Early Lung Cancer Action Project (I-ELCAP) study. Other lung cancers do not follow an orderly progression and become metastatic early on while the primary tumor is still small and asymptomatic. Computed tomography screening will have a diminished impact on changing the survival of patients with this type of tumor, and these patients will die of advanced lung cancer. The true effects of CT screening may not be evident for many years beyond the current study time intervals.
The study by Bach and colleagues [3] also provides insight into the possible harmful aspect of CT screening. Significantly increasing lung cancer diagnosis and surgery will have both a financial and physical impact on the population and health care system. The frequency of serious complications and the surgical mortality rate of lung cancer resection are not insignificant. For CT screening to gain widespread acceptance, its effectiveness must be proven.
Additional controversies in screening include the use of computer-assisted diagnosis. The computer programs that exist for nodule detection are useful tools to increase the sensitivity of a single radiology reading, and false-positive and false-negative results are encountered during CT screening that require additional evaluation. Scanning with F18-fluorodeoxyglucose (FDG) and positron emission tomography (PET) can predict the probability of malignancy, although it is also subject to false-positive and false-negative results. Transthoracic needle biopsy is used for preoperative diagnosis. The greatest effect of needle biopsy is when it provides a specific benign diagnosis, thereby obviating a surgical procedure.
Guidelines for the follow-up and management of small pulmonary nodules (< 8 mm diameter) detected incidentally on CT scan were proposed by the Fleischner Society in 2005 [6]. These guidelines are based on nodule size and the patient’s risk factors for malignancy. These recommendations take into account the fact that the probability that a given nodule is malignant increases according to its size. They also account for the fact that cigarette smokers are at a greater risk for lethal carcinomas because malignant nodules in smokers grow faster on average than in nonsmokers. For nodules larger than 8 mm, management includes follow-up CT, dynamic contrast-enhanced CT, PET, percutaneous biopsy, and thorascopic resection. The patient’s age and comorbid conditions should influence management. Although increasing patient age generally correlates with increasing likelihood of malignancy, conservative management is generally appropriate for nodules in very elderly patients or in those with comorbid disease.
Detection and evaluation of lung cancer is still in evolution [7, 8]. The management of each patient needs to be individualized by risk and other health issues. Management also needs to incorporate different technologies and procedures. Currently, there are ongoing clinical trials that aim to prove the utility of CT screening for lung cancer. The National Lung Screening Trial (NLST) is a current randomized controlled trial of more than 53,000 subjects. It is designed to minimize the impact of the multiple biases that the I-ELCAP study was criticized for. The results of this trial are expected by the year 2009 [9].
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