July 07, 2020
Individuals with a smoking history should begin annual screening for lung cancer at age 50 years instead of age 55 years, according to a draft recommendation issued by the U.S. Preventive Services Task Force.
The recommendation, an update of USPSTF guidance on lung cancer screening issued 7 years ago, also reduces smoking pack-year eligibility criteria, from 30 pack-years to 20 pack-years. It continues to apply to those who currently smoke or quit within the past 15 years.
The USPSTF considers this a “B” recommendation, concluding “with moderate certainty that annual screening for lung cancer with [low-dose CT] is of moderate net benefit in persons at high risk for lung cancer based on age, total cumulative exposure to tobacco smoke and years since quitting smoking,” according to the recommendation statement.
“New evidence provides proof that there are real benefits to starting to screen at a younger age and among people with lighter smoking history,” USPSTF member Michael J. Barry, MD, medical director of the Stoeckle Center for Primary Care Innovation at Massachusetts General Hospital, said in a press release. “We can not only save more lives, we can also help people stay healthy longer.”
Lung cancer is the leading cause of cancer-related death in the United States, according to the recommendation statement, with an estimated 228,820 diagnoses and 135,720 deaths expected this year. Smoking is the No. 1 cause of lung cancer, and smokers have an approximately 20-fold higher relative risk for the disease than nonsmokers.
Five-year lung cancer survival rates have improved, from about 16% between 1995 and 2001 to 18.6% between 2008 and 2014 for all stages combined, according to an evidence review accompanying the draft recommendation. However, prognosis remains poor.
Screening benefits, harms
Investigators reviewed evidence from 223 publications on the effectiveness, accuracy and harms of screening for lung cancer with low-dose CT (LDCT) for primary care populations in the United States.
Only two of the seven randomized controlled trials (n = 86,486) that assessed lung cancer screening with LDCT — the National Lung Screening Trial (NLST) and Nederlands-Leuvens Longkanker Screenings Onderzoek (NELSON) trial — were adequately powered, the researchers wrote.
Results of the NLST (n = 53,454) showed a reduction in lung cancer mortality (incidence rate ratio [IRR] = 0.85; 95% CI, 0.75-0.96) and all-cause mortality (IRR = 0.93; 95% CI, 0.88-0.99) with three rounds of annual LDCT screening vs. chest X-ray among high-risk current and former smokers aged 55 to 74 years. This translated to a number needed to screen to prevent one lung cancer death of 323 over 6.5 years of follow-up.
The NELSON trial (n = 15,792) showed a reduction in lung cancer mortality (IRR = 0.75; 95% CI, 0.61-0.9) but not all-cause mortality (IRR = 1.01; 95% CI, 0.92-1.11) with four rounds of LDCT screening at increasing intervals (baseline, 1 year, 3 years and 5.5 years) vs. no screening for high-risk current and former smokers aged 50 to 74 years. This translated to a number needed to screen to prevent one lung cancer death of 130 over 10 years of follow-up.
“As noted, the NELSON trial enrolled persons ages 50 to 74 years with a lighter smoking history (half a pack per day for more than 30 years or three-fourths a pack per day for more than 25 years),” the draft recommendation states. “This trial provides empiric evidence for the benefit of screening for lung cancer with LDCT in younger persons with lighter pack-year smoking histories.”
Sensitivity of LDCT ranged from 59% to 100% (13 studies; n = 76,856) and exceeded 80% in most studies. Sensitivity was 93.1% in the NLST and 59% in the NELSON trial. Specificity ranged from 26.4% to 99.7% (13 studies; n = 75,819) and exceeded 75% in most studies, including the NLST (76.5%) and NELSON trial (95.8%).
Positive predictive values ranged from 3.3% in the NLST to 43.5% in the NELSON trial; negative predictive value ranged from 97.7% to 100%.
Evidence suggested that using the Lung-RADS classification system in the NLST would have increased specificity and decreased sensitivity. A study also showed increasing the nodule size threshold for a positive screening result would increase positive predictive value.
Screening harms included radiation-induced cancer (0.26 to 0.86 major cancers for every 1,000 people screened with 10 annual LDCTs), false-positive results that lead to unnecessary tests and invasive procedures, overdiagnosis, incidental findings, and short-term increases in distress because of indeterminate results.
False-positive results led to 17 invasive procedures for every 1,000 people screened in the NLST, according to the investigators. Using the Lung-RADS criteria would have prevented about 23% of all invasive procedures for false positives in the NLST compared with the criteria used in that trial.
Overdiagnosis estimates ranged from 0% to 67%. NLST data showed four overdiagnoses, and three lung cancer deaths averted, per 1,000 people screened over 6.5 years.
Modeling studies indicated use of risk-prediction modeling would increase the number of screen-preventable deaths, reduce the number of participants needed to screen to prevent one lung cancer death and reduce the number of false-positive selections per prevented lung cancer death compared with risk factor-based-screening.
Participants in the NLST and NELSON trial tended to be younger and more highly educated than the screening-eligible U.S. population, as well as less likely to be current smokers. These served as limitations to the studies.
‘Really good news’
Expanded lung cancer screening eligibility will benefit Black individuals and women, who tend to smoke fewer cigarettes than white men, according to the task force. Data show Black people have higher risks for lung cancer than white people.
“Some really good news from the changes to this recommendation is that it will mean more people are eligible for screening, including notably more African Americans and women,” USPSTF member John B. Wong, MD, interim chief scientific officer and chief of the division of clinical decision-making at Tufts University Medical Center, said in a press release. “Making screening for lung cancer available to people who have smoked less over time will help doctors support the health and potentially save the lives of more of their African American and female patients.”
The draft recommendation statement and draft evidence review are posted for public comment on the USPSTF website at www.uspreventiveservicetaskforce.org. Comments can be submitted between July 7 and Aug. 3 at uspreventiveservicestaskforce.org/tfcomment.htm.