This Article  • Full text  • PDF  • Correction  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on HighWire  • Citing articles on Web of Science (165)  • Contact me when this article is cited  Related Content  • Similar articles in JAMA  Topic Collections  • Men's Health  • Prostate Disease  • Oncology  • Prostate Cancer  • Pathology & Laboratory Medicine  • Alert me on articles by topic  Social Bookmarking   What's this?

Ian M. Thompson, MD; Donna Pauler Ankerst, PhD; Chen Chi, MS; M. Scott Lucia, MD; Phyllis J. Goodman, MS; John J. Crowley, PhD; Howard L. Parnes, MD; Charles A. Coltman, Jr, MD

JAMA. 2005;294:66-70.

Context  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.

Design, Setting, and Participants  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.

Main Outcome Measures  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).

Conclusion  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.

Author Affiliations: Department of Urology, University of Texas Health Science Center at San Antonio (Dr Thompson); Fred Hutchinson Cancer Research Center, Seattle, Wash (Dr Ankerst and Mss Chi and Goodman); University of Colorado, Denver (Dr Lucia); Cancer Research and Biostatistics, Seattle (Dr Crowley); National Cancer Institute, National Institutes of Health, Bethesda, Md (Dr Parnes); and Southwest Oncology Group, San Antonio (Dr Coltman).

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter     What's this?

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

Prostate specific antigen for early detection of prostate cancer: longitudinal study
Holmstrom et al.
BMJ 2009;339:b3537-b3537.
ABSTRACT | FULL TEXT  

Prostate specific antigen for detecting early prostate cancer
Ilic and Green
BMJ 2009;339:b3572-b3572.
FULL TEXT  

Screening for prostate cancer remains controversial
Stark et al.
BMJ 2009;339:b3601-b3601.
FULL TEXT  

Clinical Impact and Reliability of Pleural Fluid Mesothelin in Undiagnosed Pleural Effusions
Davies et al.
Am. J. Respir. Crit. Care Med. 2009;180:437-444.
ABSTRACT | FULL TEXT  

New Molecular Biomarkers for the Prognosis and Management of Prostate Cancer - The Post PSA Era
BICKERS and AUKIM-HASTIE
Anticancer Res 2009;29:3289-3298.
ABSTRACT | FULL TEXT  

Promoter Methylation in APC, RUNX3, and GSTP1 and Mortality in Prostate Cancer Patients
Richiardi et al.
JCO 2009;27:3161-3168.
ABSTRACT | FULL TEXT  

Test Sensitivity in the European Prostate Cancer Screening Trial: Results from Finland, Sweden, and the Netherlands
Auvinen et al.
Cancer Epidemiol. Biomarkers Prev. 2009;18:2000-2005.
ABSTRACT | FULL TEXT  

Development and validation of a dynamic prognostic tool for prostate cancer recurrence using repeated measures of posttreatment PSA: a joint modeling approach
Proust-Lima and Taylor
Biostatistics 2009;10:535-549.
ABSTRACT | FULL TEXT  

Screening for Prostate Cancer
Brawley et al.
CA Cancer J Clin 2009;59:264-273.
ABSTRACT | FULL TEXT  

Cumulative Incidence of False-Positive Results in Repeated, Multimodal Cancer Screening
Croswell et al.
Ann Fam Med 2009;7:212-222.
ABSTRACT | FULL TEXT  

Diagnostic Accuracy of Predicting Somatization From Patients' ICD-9 Diagnoses
Smith et al.
Psychosom. Med. 2009;71:366-371.
ABSTRACT | FULL TEXT  

Genetic Variants and Family History Predict Prostate Cancer Similar to Prostate-Specific Antigen
Zheng et al.
Clin. Cancer Res. 2009;15:1105-1111.
ABSTRACT | FULL TEXT  

Emerging Biomarkers for the Diagnosis and Prognosis of Prostate Cancer
Sardana et al.
Clin. Chem. 2008;54:1951-1960.
ABSTRACT | FULL TEXT  

Prostate-Specific Antigen: A Misused and Maligned Prostate Cancer Biomarker
Thompson et al.
JNCI J Natl Cancer Inst 2008;100:1487-1488.
FULL TEXT  

Pathologic Characteristics of Cancers Detected in the Prostate Cancer Prevention Trial: Implications for Prostate Cancer Detection and Chemoprevention
Lucia et al.
Cancer Prevention Research 2008;1:167-173.
ABSTRACT | FULL TEXT  

Five Genetic Variants Associated with Prostate Cancer
Coates et al.
NEJM 2008;358:2738-2741.
FULL TEXT  

Development of a Multiplexed Urine Assay for Prostate Cancer Diagnosis
Vener et al.
Clin. Chem. 2008;54:874-882.
ABSTRACT | FULL TEXT  

Commentary: How Serious Is Getting a Diagnosis of Prostate Cancer?
Barry
The Oncologist 2008;13:306-308.
FULL TEXT  

Baseline Prostate-Specific Antigen Level and Risk of Prostate Cancer and Prostate-Specific Mortality: Diagnosis Is Dependent on the Intensity of Investigation
Connolly et al.
Cancer Epidemiol. Biomarkers Prev. 2008;17:271-278.
ABSTRACT | FULL TEXT  

'A matter of faith, not science': analysis of media coverage of prostate cancer screening in Australian news media 2003-2006
MacKenzie et al.
JRSM 2007;100:513-521.
ABSTRACT | FULL TEXT  

Imaging in Oncology from The University of Texas M. D. Anderson Cancer Center: Diagnosis, Staging, and Surveillance of Prostate Cancer
Kundra et al.
Am. J. Roentgenol. 2007;189:830-844.
ABSTRACT | FULL TEXT  

Assessing Individual Risk for Prostate Cancer
Nam et al.
JCO 2007;25:3582-3588.
ABSTRACT | FULL TEXT  

Prediction of Prostate Cancer for Patients Receiving Finasteride: Results From the Prostate Cancer Prevention Trial
Thompson et al.
JCO 2007;25:3076-3081.
ABSTRACT | FULL TEXT  

Rebuttal: Should Canadians be offered systematic prostate cancer screening?: NO
Labrecque et al.
cfp 2007;53:1140-1141.
FULL TEXT  

Refutation: Devrait-on offrir aux Canadiens le depistage systematique du cancer de la prostate?: NON
Labrecque et al.
cfp 2007;53:1142-1143.
FULL TEXT  

Hunting for a pleural fluid test for mesothelioma: is soluble mesothelin the answer?
Lee
Thorax 2007;62:561-562.
FULL TEXT  

Prostate-specific antigen in the early detection of prostate cancer
Thompson and Ankerst
CMAJ 2007;176:1853-1858.
ABSTRACT | FULL TEXT  

Akt/cAMP-Responsive Element Binding Protein/Cyclin D1 Network: A Novel Target for Prostate Cancer Inhibition in Transgenic Adenocarcinoma of Mouse Prostate Model Mediated by Nexrutine, a Phellodendron Amurense Bark Extract
Kumar et al.
Clin. Cancer Res. 2007;13:2784-2794.
ABSTRACT | FULL TEXT  

Commentary: The ubiquity of prostate cancer: echoes of the past, implications for the present
Thompson et al.
Int J Epidemiol 2007;0:dym056v1-3.
FULL TEXT  

Prostate-Specific Antigen Levels, Prostate-Specific Antigen Kinetics, and Prostate Cancer Prognosis: A Tocsin Calling for Prospective Studies
Parekh et al.
JNCI J Natl Cancer Inst 2007;99:496-497.
FULL TEXT  

Commentary: Prostate cancer is omnipresent, but should we screen for it?
Martin
Int J Epidemiol 2007;36:278-281.
FULL TEXT  

Long-Term Prediction of Prostate Cancer Up to 25 Years Before Diagnosis of Prostate Cancer Using Prostate Kallikreins Measured at Age 44 to 50 Years
Lilja et al.
JCO 2007;25:431-436.
ABSTRACT | FULL TEXT  

Plasma pro-B-type natriuretic peptide in the general population: screening for left ventricular hypertrophy and systolic dysfunction
Goetze et al.
Eur Heart J 2006;27:3004-3010.
ABSTRACT | FULL TEXT  

Detection of life-threatening prostate cancer with prostate-specific antigen velocity during a window of curability.
Carter et al.
JNCI J Natl Cancer Inst 2006;98:1521-1527.
ABSTRACT | FULL TEXT  

A systematic method for selection of promising serum protein biomarkers to improve prostate cancer (PCa1) detection.
Finlay et al.
Clin. Chem. 2006;52:2159-2162.
FULL TEXT  

Histopathology as a Predictive Biomarker: Strengths and Limitations
Cardiff et al.
J. Nutr. 2006;136:2673S-2675S.
FULL TEXT  

PSA: A Biomarker for Disease. A Biomarker for Clinical Trials. How Useful Is It?
Thompson
J. Nutr. 2006;136:2704S-2704S.
FULL TEXT  

Effect of Finasteride on the Sensitivity of PSA for Detecting Prostate Cancer.
Thompson et al.
JNCI J Natl Cancer Inst 2006;98:1128-1133.
ABSTRACT | FULL TEXT  

Assessing risk: does this patient have prostate cancer?
Carter
JNCI J Natl Cancer Inst 2006;98:506-507.
FULL TEXT  

Assessing prostate cancer risk: results from the Prostate Cancer Prevention Trial.
Thompson et al.
JNCI J Natl Cancer Inst 2006;98:529-534.
ABSTRACT | FULL TEXT  

Aberrant Methylation and Deacetylation of Deleted in Liver Cancer-1 Gene in Prostate Cancer: Potential Clinical Applications
Guan et al.
Clin. Cancer Res. 2006;12:1412-1419.
ABSTRACT | FULL TEXT  

Evaluating markers for the early detection of cancer: overview of study designs and methods
Baker et al.
Clin Trials 2006;3:43-56.
ABSTRACT  

2-Methoxyestradiol Inhibits Prostate Tumor Development in Transgenic Adenocarcinoma of Mouse Prostate: Role of Tumor Necrosis Factor-{alpha}-Stimulated Gene 6
Garcia et al.
Clin. Cancer Res. 2006;12:980-988.
ABSTRACT | FULL TEXT  

American Cancer Society Guidelines for the Early Detection of Cancer, 2006
Smith et al.
CA Cancer J Clin 2006;56:11-25.
ABSTRACT | FULL TEXT  

Operating Characteristics of Prostate-Specific Antigen and Verification Bias
Punglia et al.
JAMA 2005;294:2698-2698.
FULL TEXT  

Stage Migration and Grade Inflation in Prostate Cancer: Will Rogers Meets Garrison Keillor
Thompson et al.
JNCI J Natl Cancer Inst 2005;97:1236-1237.
FULL TEXT  

Study highlights insensitivity of PSA screening
Mayor
BMJ 2005;331:67-67.
FULL TEXT