Lung cancer screening: current status

Lung cancer remains the leading cause of death from malignancy with approximately 1.3 million deaths occurring world wide per year [1]. Approximately 70 % of cases have incurable disease at presentation which is either widely metastatic or locally advanced [1]. The overall 5-year survival still remains very low at only 14 % [1]. Lung cancer, however, which is detected early in its course, demonstrates much better survival data. Survival in non-small-cell lung cancer Stage I is greater than 70 % and small peripheral less than 1 cm lung cancers have survival rates of greater than 80 % [2]. The rationale for screening is, therefore, obvious. Diagnosis of lung cancer early in preclinical stages has a higher cure rate and, therefore, high-risk asymptomatic individuals are likely to benefit from screening. The introduction of helical and subsequently multidetector CT in the 1990s led to a number of feasibility studies in which CT was used as a screening tool for the detection of early asymptomatic lung cancer. Observational single arm trials were conducted for several years in many countries including the United States, Japan, and Europe [3–8]. These studies established the sensitivity of low-dose CT for early lung cancer detection. These trials also tested algorithms for diagnostic workup and demonstrated a reduction in the incidence of advanced non-small-cell lung cancer with screening. A high percentage (84–93 %) was Stage I lung cancers [3–5]. They also produced somewhat similar results. They demonstrated that detection of earlystage lung cancer was higher than that reported previously with standard chest radiography [9] but that the false positive rate was at least three times that of standard radiographs. In regard to diagnostic algorithms, these studies provided evidence that peripheral nodules greater than 8–10 mm in size required further investigation because of the high likelihood of lung cancer. Such investigations included further imaging with PET–CT, percutaneous biopsy or resection and often led to invasive procedures. Smaller nodules (\8 mm diameter) could be managed with CT follow-up to determine interval growth indicating the likelihood of malignancy. These single arm feasibility and observational studies provided compelling evidence of the effectiveness of helical and MDCT as a screening tool for early detection of lung cancer. However, they were not sufficient to determine screening effectiveness because they were not able to assess the influence of CT screening on lung cancer mortality. Only randomized controlled trials can determine effectiveness of screening where the end point must be a decrease in mortality in the screened group as compared to a non-screened control. Subsequently, several prospective randomized controlled trials were undertaken both in the United States and Europe. These included the National Lung Cancer Screening Trial (NLST) in the United States [10] and the Nelson Trial and others in Europe [11–15]. The results of the NLST trial were published in 2011 [16]. The trial was a cooperative effort between the National Cancer Institute of the NIH and ACRIN, the American College of Radiology Imaging Network. 53,454 individuals were enrolled in the trial. It was a randomized national study and the population group included individuals between the ages of 55 and 74 with history of C30-pack years of current or prior smoking. The enrollees underwent three annual screens. The study group received low-dose CT and the control group underwent standard chest radiography. CT was conducted with T. C. McLoud (&) Thoracic Radiology, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, Boston, MA 02114, USA e-mail: tmcloud@partners.org