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.


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


METHODS
Feasibility study for the ongoing National Lung Screening Trial.


METHODS
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).


METHODS
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.


METHODS
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.


CONCLUSIONS
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.


CONCLUSIONS
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.


BACKGROUND
National Cancer Institute.
Croswell
Jennifer M
JM
National Institutes of Health, National Cancer Institute, Bethesda, and Information Management Services, Rockville, Maryland 20892, USA. croswellj@od.nih.gov
Baker
Stuart G
SG
Marcus
Pamela M
PM
Clapp
Jonathan D
JD
Kramer
Barnett S
BS
D000368:Aged; D055088:Early Detection of Cancer / Q000379:methods / Q000592:standards*; D005189:False Positive Reactions; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000000981:diagnostic imaging*; D008297:Male; D008400:Mass Chest X-Ray; D008403:Mass Screening / Q000379:methods / Q000592:standards*; D008875:Middle Aged; D010349:Patient Compliance; D014057:Tomography, X-Ray Computed; D019564:Unnecessary Procedures