The German Lung Cancer Screening Intervention Trial (LUSI) shows that the early repeat scan rate for suspicious findings decreased by more than 80% with the second and subsequent low-dose computed tomography (LDCT) screens, but emphasizes the need to have an organized screening program with the baseline scan available for comparison.
In the United States the National Lung Cancer Screening Trial (NLST) showed that annual lung cancer screening of high-risk individuals with LDCT reduces lung cancer mortality by 20% and overall mortality by 7%. There are now multiple lung cancer screening trials ongoing throughout the world, but one concern is the high number of early repeat scans for suspicious findings that are in fact not lung cancer. This high number of false positives could make screening impractical due to cost, invasive follow-up procedures, and anxiety for the patients.
The LUSI is comparing no intervention (n=2023) to 5 annual screens of individuals’ aged 50-69 with a history of heavy tobacco smoking (n=2029). All the participants have been followed for at least 3 years but many have been followed for 5 years. The control arm is tracked with an annual questionnaire and query of cancer registries. The LUSI is ongoing but the current analyses compare the first screening round to subsequent rounds with regard to performance indicators, such as early recall rate, detection rate, and interval cancer rate.
The results published in the Journal of Thoracic Oncology, the official journal of the International Association for the Study of Lung Cancer, show that there was a strong decline in the early recall rate from 20% in the first screening round to 3-4% in rounds 2-4 (p<0.0001).
The detection of lung cancer was 1.1% in the first round but then declined to 0.5%, on average, for the subsequent rounds. The cumulative number of advanced lung cancers was almost identical between the control and intervention groups for the first two years but by year three the number of advanced cancers in the screening group began to decline. The same trend was observed for the overall mortality.
Can lung cancer be found early?
Usually symptoms of lung cancer do not appear until the disease is already in an advanced, non-curable stage. Even when symptoms of lung cancer do appear, many people may mistake them for other problems, such as an infection or long-term effects from smoking. This may delay the diagnosis.
Some lung cancers are diagnosed early because they are found by accident as a result of tests for other medical conditions. For example, lung cancer may be found by imaging tests (such as a chest x-ray or chest CT scan), bronchoscopy (viewing the inside of lung airways through a flexible lighted tube), or sputum exam (microscopic examination of cells in coughed up phlegm) done for other reasons in patients with heart disease, pneumonia, or other lung conditions. A small portion of these patients do very well and may be cured of lung cancer.
Screening is the use of tests or exams to detect a disease in people without symptoms of that disease. Doctors have looked for many years for a test to find lung cancer early and help people live longer, but only in recent years has a study shown that a lung cancer screening test can help lower the risk of dying from this disease.
The authors conclude “our data indicate that the most prominent side effect “false positive alarm” cannot be controlled if the choice of doctor is at the screenee’s discretion at every annual screening visit. The early recall rates of rounds 2-4 would have been around 30%, instead of 3-4%, if the prior scans were not available. Thus, a potential lung cancer screening program must be organized such that all previous images and results are available.”
Lung cancer is the third most common cancer and the leading cause of cancer-related death in the United States. The most important risk factor for lung cancer is smoking, which results in approximately 85% of all U.S. lung cancer cases. Although the prevalence of smoking has decreased, approximately 37% of U.S. adults are current or former smokers. The incidence of lung cancer increases with age and occurs most commonly in persons aged 55 years or older. Increasing age and cumulative exposure to tobacco smoke are the 2 most common risk factors for lung cancer.
Lung cancer has a poor prognosis, and nearly 90% of persons with lung cancer die of the disease. However, early-stage non-small cell lung cancer (NSCLC) has a better prognosis and can be treated with surgical resection.
Most lung cancer cases are NSCLC, and most screening programs focus on the detection and treatment of early-stage NSCLC. Although chest radiography and sputum cytologic evaluation have been used to screen for lung cancer, LDCT has greater sensitivity for detecting early-stage cancer.
Benefits of Detection and Early Treatment
Although lung cancer screening is not an alternative to smoking cessation, the USPSTF found adequate evidence that annual screening for lung cancer with LDCT in a defined population of high-risk persons can prevent a substantial number of lung cancer-related deaths. Direct evidence from a large, well-conducted, randomized, controlled trial (RCT) provides moderate certainty of the benefit of lung cancer screening with LDCT in this population. The magnitude of benefit to the person depends on that person’s risk for lung cancer because those who are at highest risk are most likely to benefit. Screening cannot prevent most lung cancer-related deaths, and smoking cessation remains essential.
Harms of Detection and Early Intervention and Treatment
The harms associated with LDCT screening include false-negative and false-positive results, incidental findings, overdiagnosis, and radiation exposure. False-positive LDCT results occur in a substantial proportion of screened persons; 95% of all positive results do not lead to a diagnosis of cancer. In a high-quality screening program, further imaging can resolve most false-positive results; however, some patients may require invasive procedures.
The USPSTF found insufficient evidence on the harms associated with incidental findings. Overdiagnosis of lung cancer occurs, but its precise magnitude is uncertain. A modeling study performed for the USPSTF estimated that 10% to 12% of screen-detected cancer cases are overdiagnosed - that is, they would not have been detected in the patient’s lifetime without screening. Radiation harms, including cancer resulting from cumulative exposure to radiation, vary depending on the age at the start of screening; the number of scans received; and the person’s exposure to other sources of radiation, particularly other medical imaging.
About the IASLC:
The International Association for the Study of Lung Cancer (IASLC) is the only global organization dedicated to the study of lung cancer. Founded in 1974, the association’s membership includes more than 4,000 lung cancer specialists in 80 countries.