Operating characteristics of prostate-specific antigen in men with an initial PSA level of 3.0 ng/ml or lower.
BACKGROUND
Three fourths of US men older than 50 years have been screened with prostate-specific antigen (PSA) for prostate cancer.


OBJECTIVE
To estimate the receiver operating characteristic (ROC) curve for PSA.


METHODS
Calculation of PSA ROC curves in the placebo group of the Prostate Cancer Prevention Trial, a randomized, prospective study conducted from 1993 to 2003 at 221 US centers. Participants were 18 882 healthy men aged 55 years or older without prostate cancer and with PSA levels less than or equal to 3.0 ng/mL and normal digital rectal examination results, followed up for 7 years with annual PSA measurement and digital rectal examination. If PSA level exceeded 4.0 ng/mL or rectal examination result was abnormal, a prostate biopsy was recommended. After 7 years of study participation, an end-of-study prostate biopsy was recommended in all cancer-free men.


METHODS
Operating characteristics of PSA for prostate cancer detection, including sensitivity, specificity, and ROC curve.


RESULTS
Of 8575 men in the placebo group with at least 1 PSA measurement and digital rectal examination in the same year, 5587 (65.2%) had had at least 1 biopsy; of these, 1225 (21.9%) were diagnosed with prostate cancer. Of 1213 cancers with Gleason grade recorded, 250 (20.6%) were Gleason grade 7 or greater and 57 (4.7%) were Gleason grade 8 or greater. The areas under the ROC curve (AUC) for PSA to discriminate any prostate cancer vs no cancer, Gleason grade 7 or greater cancer vs no or lower-grade cancer, and Gleason grade 8 or greater cancer vs no or lower-grade cancer were 0.678 (95% confidence interval [CI], 0.666-0.689), 0.782 (95% CI, 0.748-0.816), and 0.827 (95% CI, 0.761-0.893), respectively (all P values <.001 for AUC vs 50%). For detecting any prostate cancer, PSA cutoff values of 1.1, 2.1, 3.1, and 4.1 ng/mL yielded sensitivities of 83.4%, 52.6%, 32.2%, and 20.5%, and specificities of 38.9%, 72.5%, 86.7%, and 93.8%, respectively. Age-stratified analyses showed slightly better performance of PSA in men younger than 70 years vs those 70 years or older with AUC values of 0.699 (SD, 0.013) vs 0.663 (SD, 0.013) (P = .03).


CONCLUSIONS
There is no cutpoint of PSA with simultaneous high sensitivity and high specificity for monitoring healthy men for prostate cancer, but rather a continuum of prostate cancer risk at all values of PSA.
Thompson
Ian M
IM
Department of Urology, University of Texas Health Science Center at San Antonio, TX 78229, USA. thompsoni@uthscsa.edu
Ankerst
Donna Pauler
DP
Chi
Chen
C
Lucia
M Scott
MS
Goodman
Phyllis J
PJ
Crowley
John J
JJ
Parnes
Howard L
HL
Coltman
Charles A
CA
D000368:Aged; D001706:Biopsy; D006801:Humans; D008297:Male; D008875:Middle Aged; D011467:Prostate / Q000473:pathology; D017430:Prostate-Specific Antigen / Q000097:blood*; D011471:Prostatic Neoplasms / Q000097:blood / Q000175:diagnosis*; D012372:ROC Curve; D012016:Reference Values; D012680:Sensitivity and Specificity
D017430:Prostate-Specific Antigen