AIM: Lung cancer CT screening can yield high false-positive rates

CT scans measuring blood flow in the lungs can detect early emphysema-related changes that occur in smokers who are susceptible to the disease. Image source: Courtesy of Eric Hoffman, PhD, department of radiology, University of Iowa Carver College of Medicine

The risk for false-positive results on lung cancer screening tests is substantial following only two annual exams, particularly for low-dose CT, based on the results of a study published in the April issue of Annals of Internal Medicine.

Researchers from the National Institutes of Health, National Cancer Institute in Bethesda, Md., sought to quantify the cumulative risk facing an individual participating in a one- or two-year lung cancer screening exam, based on at least one false-positive finding. In addition to determining the rates of false-positive findings, lead author Jennifer M. Croswell, MD, and colleagues identified rates of unnecessary diagnostic procedures that are potentially brought on by these false-positive findings.

The authors wrote, “direct-to-consumer promotion of lung cancer screening has increased, especially low-dose CT. However, screening exposes healthy persons to potential harms, and cumulative false-positive rates for low-dose CT have never been formally reported.”

The randomized, controlled two-year study conducted in six centers of low-dose CT--which the researchers compared to chest radiography--recruited a cohort of 3,318 current or former smokers who had quit in the past 10 years between the ages of 55-74 from the ongoing National Lung Screening Trial, all of whom had a smoking history of 30 pack-years or more and no history of lung cancer. 

The researchers randomly assigned the participants to low-dose CT or chest radiography with baseline and one repeated annual screening, and follow-up was conducted at one year after the final screening. Assignment was concentrated and stratified by age, sex and study center.

Croswell and colleagues took note of any false-positive screenings, defined as a positive screening with a completed negative work up or 12 months or more of follow up with no lung cancer diagnosis.

By way of a Kaplan-Meier analysis, the researchers determined that an individual’s cumulative probability of one or more false-positive finding from low-dose CT examinations was 21 percent after one screening and 33 percent following the second exam. The false-positive rates for chest radiography however following the first exam were 9 percent and 15 percent after the second screening.

In addition, the authors wrote that “more than half of participants with false-positive chest radiography or CT had at least one additional imaging exam—some at higher radiation doses than that of the original test—which exposed these persons to a theoretical risk for radiation-induced carcinogenesis.”

Moreover, they found that a total of 7 percent of participants with a false-positive low-dose CT exam and 4 percent with a false-positive chest radiography result underwent a resulting invasive procedure.

Noting that the study was limited to two rounds of exams and follow-up after the second screening was limited to 12 months, the researchers said that the false-negative rate is most likely underestimated and that further study of resulting economic, psychosocial and physical burdens of these methods is necessary.