Cumulative incidence of false-positive results in repeated, multimodal cancer screening.
OBJECTIVE
Multiple cancer screening tests have been advocated for the general population; however, clinicians and patients are not always well-informed of screening burdens. We sought to determine the cumulative risk of a false-positive screening result and the resulting risk of a diagnostic procedure for an individual participating in a multimodal cancer screening program.


METHODS
Data were analyzed from the intervention arm of the ongoing Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial, a randomized controlled trial to determine the effects of prostate, lung, colorectal, and ovarian cancer screening on disease-specific mortality. The 68,436 participants, aged 55 to 74 years, were randomized to screening or usual care. Women received serial serum tests to detect cancer antigen 125 (CA-125), transvaginal sonograms, posteroanterior-view chest radiographs, and flexible sigmoidoscopies. Men received serial chest radiographs, flexible sigmoidoscopies, digital rectal examinations, and serum prostate-specific antigen tests. Fourteen screening examinations for each sex were possible during the 3-year screening period.


RESULTS
After 14 tests, the cumulative risk of having at least 1 false-positive screening test is 60.4% (95% CI, 59.8%-61.0%) for men, and 48.8% (95% CI, 48.1%-49.4%) for women. The cumulative risk after 14 tests of undergoing an invasive diagnostic procedure prompted by a false-positive test is 28.5% (CI, 27.8%-29.3%) for men and 22.1% (95% CI, 21.4%-22.7%) for women.


CONCLUSIONS
For an individual in a multimodal cancer screening trial, the risk of a false-positive finding is about 50% or greater by the 14th test. Physicians should educate patients about the likelihood of false positives and resulting diagnostic interventions when counseling about cancer screening.
Office of the Director, Office of Disease Prevention, National Institutes of Health, 6100 Executive Blvd, Suite 2B-03, Bethesda, MD 20892, USA. croswellj@od.nih.gov
Jennifer Miller
JM
Croswell
Barnett S
BS
Kramer
Aimee R
AR
Kreimer
Phil C
PC
Prorok
Jian-Lun
JL
Xu
Stuart G
SG
Baker
Richard
R
Fagerstrom
Thomas L
TL
Riley
Jonathan D
JD
Clapp
Christine D
CD
Berg
John K
JK
Gohagan
Gerald L
GL
Andriole
David
D
Chia
Timothy R
TR
Church
E David
ED
Crawford
Mona N
MN
Fouad
Edward P
EP
Gelmann
Lois
L
Lamerato
Douglas J
DJ
Reding
Robert E
RE
Schoen
D000368:Aged; D018394:CA-125 Antigen / Q000097:blood; D015179:Colorectal Neoplasms / Q000175:diagnosis*; D005189:False Positive Reactions; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis*; D008297:Male; D008403:Mass Screening / Q000379:methods / Q000592:standards*; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000097:blood / Q000175:diagnosis*; D017430:Prostate-Specific Antigen / Q000592:standards; D011471:Prostatic Neoplasms / Q000097:blood / Q000175:diagnosis*; D012680:Sensitivity and Specificity; D012812:Sigmoidoscopy / Q000592:standards
D018394:CA-125 Antigen; D017430:Prostate-Specific Antigen