Screening would lead to 50% cancer cases detected early
The National Lung Screening Trial (NLST) demonstrated that three annual computed tomography (CT) screenings reduced lung cancer specific mortality by 20% compared with annual chest radiography screenings in a volunteer population of current and former smokers ages 55 to 74 years with at least 30 pack years of cigarette smoking history and no more than 15 years since quitting for former smokers.
In this new study researchers evaluated the benefits and harms of CT screening programs that varied by age, pack year, years since quitting and frequency of screening.
For the study researchers used 5 models calibrated to individual-level, de-identified data from the NLST and the Prostate, Lung, Colorectal, and Ovarian Cancer (PLCO) screening trial.
The NLST enrolled 53, 452 persons at high risk for lung cancer at 33 U.S. centers from August 2002 through April 2004. Participants were randomly assigned to undergo 3 annual screening examinations with low-dose CT (26,722 participants) or single-view posterior–anterior chest radiography (26,730 participants).
The PLCO trial randomly assigned 154,901 participants age 55 through 74 years at entry, 77,445 of who were assigned to annual chest radiography and 77,456 to usual care between November 1993 and July 2001.
There was no eligibility requirement concerning smoking. Although the PLCO trial compared chest radiography with no screening, it provided information on the natural history of lung cancer.
Groups of investigators at the following 5 institutions independently developed the models. The investigators came from Erasmus Medical Center in Rotterdam, the Netherlands, Fred Hutchinson Cancer Research Center in Seattle, Washington, the Massachusetts General Hospital in Boston, Massachusetts, Stanford University in Stanford, California and the University of Michigan in Ann Arbor, Michigan.
The researchers evaluated 576 scenarios with annual or less frequent screening of persons between 45 and 85 years, for a range of minimum smoking exposure (packs per year) and maximum time since quitting. Screening benefits were evaluated in percentages of cancer detected by early stage (I and II), percentage of absolute number of lung cancer deaths prevented and life years gained compared to those who did not have screening. Screening harms were evaluated by the number of CT scans required, number of follow-up imaging examinations, number of over-diagnosed lung cancers and related radiation lung cancer deaths.
The researchers focused on 26 efficient screening scenarios with screening age starting at 50, 55 or 60 years. Among these 26, screening done every three years and reduced total lung cancer mortality by five to six percent compared to screening done every two years and reduced cancer mortality by seven to ten percent. Screening done yearly had reduced cancer mortality by 11 to 21%.
Researchers then examined annual screenings that started at 55 or 60 years and ended at age 80 years. The screenings equaled 200,000 to 600,000 screening per 100,000 persons,
The team then added in a lower-intensity reference scenario that equaled eight programs that was like the NLST criteria except for stopping age. Annual screening started at age 55 years and ended at age 80 for 30 year pack smokers and no more than 15 years of since quitting for former smokers.
Among these eight programs, 19.3% of participants would have screening done at least once that equaled 287,000 CT screenings per 100,000 persons, resulting in 50% of lung cancers being detected at an early stage and a 14% reduction (520 per 100,00 persons) in lung cancer mortality which resulted in about 5,500 life years gaining per 100,000 persons.
The team found the benefits outweighed the harms; 330,000 CT exams per 100,000 persons that included follow-up scans. The harms resulted in 4% over-diagnosis of all lung cancers and 0.8% of lung cancer deaths (24 deaths per 100,000 persons) related to radiation exposure.
In their conclusion the team writes “Our findings support a range of possible lung cancer screening programs, including annual lung cancer screening of individuals with at least 30 pack years of smoking that are between the ages of 55 and 80 years, but cannot determine which tradeoff of harms and benefits is best. Scenarios with an older starting age (60 years), but increased maximum years since quitting (from 15 to 25 years) offer different tradeoffs of benefits and harms (depending on the minimum packs per years). Extending eligibility to individuals with fewer packs per year although still inefficient, leads to additional benefits but more additional harms.”
“Our models show that annual lung cancer screening of individuals with a smoking history of at least 30 pack-years from ages 55 through 80 years offer substantial benefits. There would be a 14% overall lung cancer mortality reduction and a 25% reduction in those eligible for screening, with relatively limited harms,” write the researchers.
This study appears in the Annals of Internal Medicine.