Cumulative incidence of false-positive test results in lung cancer screening: a randomized trial.

BACKGROUND

Direct-to-consumer promotion of lung cancer screening has increased, especially low-dose computed tomography (CT). However, screening exposes healthy persons to potential harms, and cumulative false-positive rates for low-dose CT have never been formally reported.

OBJECTIVE

To quantify the cumulative risk that a person who participated in a 1- or 2-year lung cancer screening examination would receive at least 1 false-positive result, as well as rates of unnecessary diagnostic procedures.

DESIGN

Randomized, controlled trial of low-dose CT versus chest radiography. (ClinicalTrials.gov registration number: NCT00006382)

SETTING

Feasibility study for the ongoing National Lung Screening Trial.

PATIENTS

Current or former smokers, aged 55 to 74 years, with a smoking history of 30 pack-years or more and no history of lung cancer (n = 3190).

INTERVENTION

Random assignment to low-dose CT or chest radiography with baseline and 1 repeated annual screening; 1-year follow-up after the final screening. Randomization was centralized and stratified by age, sex, and study center.

MEASUREMENTS

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.

RESULTS

By using a Kaplan-Meier analysis, a person's cumulative probability of 1 or more false-positive low-dose CT examinations was 21% (95% CI, 19% to 23%) after 1 screening and 33% (CI, 31% to 35%) after 2. The rates for chest radiography were 9% (CI, 8% to 11%) and 15% (CI, 13% to 16%), respectively. A total of 7% of participants with a false-positive low-dose CT examination and 4% with a false-positive chest radiography had a resulting invasive procedure.

LIMITATIONS

Screening was limited to 2 rounds. Follow-up after the second screening was limited to 12 months. The false-negative rate is probably an underestimate.

CONCLUSION

Risks for false-positive results on lung cancer screening tests are substantial after only 2 annual examinations, particularly for low-dose CT. Further study of resulting economic, psychosocial, and physical burdens of these methods is warranted.

PRIMARY FUNDING SOURCE

National Cancer Institute.