Use of the percentage of free prostate-specific antigen to enhance differentiation of prostate cancer from benign prostatic disease

A prospective multicenter clinical trial

William J. Catalona, Alan Wayne Partin, Kevin M. Slawin, Michael K. Brawer, Robert C. Flanigan, Anup Patel, Jerome P. Richie, Jean B. DeKernion, Patrick Walsh, Peter T. Scardino, Paul H. Lange, Eric N P Subong, Robert E. Parson, Gail H. Gasior, Kathleen G. Loveland, Paula C. Southwick

Research output: Contribution to journalArticle

Abstract

Context. - The percentage of free prostate-specific antigen (PSA) in serum has been shown to enhance the specificity of PSA testing for prostate cancer detection, but earlier studies provided only preliminary cutoffs for clinical use. Objective. - To develop risk assessment guidelines and a cutoff value for defining abnormal percentage of free PSA in a population of men to whom the test would be applied. Design. - Prospective blinded study using the Tandem PSA and free PSA assays (Hybritech Inc, San Diego, Calif). Setting. - Seven nationwide university medical centers. Participants. - A total of 773 men (379 with prostate cancer, 394 with benign prostatic disease) 50 to 75 years of age with a palpably benign prostate gland, PSA level of 4.0 to 10.0 ng/mL, and histologically confirmed diagnosis. Main Outcome Measures. - A percentage of free PSA cutoff that maintained 95% sensitivity for prostate cancer detection, and probability of cancer for individual patients. Results. - The percentage of free PSA may be used in 2 ways: as a single cutoff (ie, perform a biopsy for all patients at or below a cutoff of 25% free PSA) or as an individual patient risk assessment (ie, base biopsy decisions on each patient's risk of cancer). The 25% free PSA cutoff detected 95% of cancers while avoiding 20% of unnecessary biopsies. The cancers associated with greater than 25% free PSA were more prevalent in older patients, and generally were less threatening in terms of tumor grade and volume. For individual patients, a lower percentage of free PSA was associated with a higher risk of cancer (range, 8%-56%). In the multivariate model used, the percentage of free PSA was an independent predictor of prostate cancer (odds ratio [OR], 3.2; 95% confidence interval [CI], 2.5-4.1; P <.001) and contributed significantly more than age (OR, 1.2; 95% CI, 0.92-1.55) or total PSA level (OR, 1.0; 95% CI, 0.92-1.11) in this cohort of subjects with total PSA values between 4.0 and 10.0 ng/mL. Conclusions. - Use of the percentage of free PSA can reduce unnecessary biopsies in patients undergoing evaluation for prostate cancer, with a minimal loss in sensitivity in detecting cancer. A cutoff of 25% or less free PSA is recommended for patients with PSA values between 4.0 and 10.0 ng/mL and a palpably benign gland, regardless of patient age or prostate size. To our knowledge, this study is the largest series to date evaluating the percentage of free PSA in a population representative of patients in whom the test would be used in clinical practice.

Original languageEnglish (US)
Pages (from-to)1542-1547
Number of pages6
JournalJournal of the American Medical Association
Volume279
Issue number19
DOIs
StatePublished - May 20 1998

Fingerprint

Prostatic Diseases
Prostate-Specific Antigen
Multicenter Studies
Prostatic Neoplasms
Clinical Trials
Biopsy
Neoplasms
Odds Ratio
Confidence Intervals
Prostate

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Use of the percentage of free prostate-specific antigen to enhance differentiation of prostate cancer from benign prostatic disease : A prospective multicenter clinical trial. / Catalona, William J.; Partin, Alan Wayne; Slawin, Kevin M.; Brawer, Michael K.; Flanigan, Robert C.; Patel, Anup; Richie, Jerome P.; DeKernion, Jean B.; Walsh, Patrick; Scardino, Peter T.; Lange, Paul H.; Subong, Eric N P; Parson, Robert E.; Gasior, Gail H.; Loveland, Kathleen G.; Southwick, Paula C.

In: Journal of the American Medical Association, Vol. 279, No. 19, 20.05.1998, p. 1542-1547.

Research output: Contribution to journalArticle

Catalona, WJ, Partin, AW, Slawin, KM, Brawer, MK, Flanigan, RC, Patel, A, Richie, JP, DeKernion, JB, Walsh, P, Scardino, PT, Lange, PH, Subong, ENP, Parson, RE, Gasior, GH, Loveland, KG & Southwick, PC 1998, 'Use of the percentage of free prostate-specific antigen to enhance differentiation of prostate cancer from benign prostatic disease: A prospective multicenter clinical trial', Journal of the American Medical Association, vol. 279, no. 19, pp. 1542-1547. https://doi.org/10.1001/jama.279.19.1542
Catalona, William J. ; Partin, Alan Wayne ; Slawin, Kevin M. ; Brawer, Michael K. ; Flanigan, Robert C. ; Patel, Anup ; Richie, Jerome P. ; DeKernion, Jean B. ; Walsh, Patrick ; Scardino, Peter T. ; Lange, Paul H. ; Subong, Eric N P ; Parson, Robert E. ; Gasior, Gail H. ; Loveland, Kathleen G. ; Southwick, Paula C. / Use of the percentage of free prostate-specific antigen to enhance differentiation of prostate cancer from benign prostatic disease : A prospective multicenter clinical trial. In: Journal of the American Medical Association. 1998 ; Vol. 279, No. 19. pp. 1542-1547.
@article{4b31ea4ac2534abf975488a6c9b89247,
title = "Use of the percentage of free prostate-specific antigen to enhance differentiation of prostate cancer from benign prostatic disease: A prospective multicenter clinical trial",
abstract = "Context. - The percentage of free prostate-specific antigen (PSA) in serum has been shown to enhance the specificity of PSA testing for prostate cancer detection, but earlier studies provided only preliminary cutoffs for clinical use. Objective. - To develop risk assessment guidelines and a cutoff value for defining abnormal percentage of free PSA in a population of men to whom the test would be applied. Design. - Prospective blinded study using the Tandem PSA and free PSA assays (Hybritech Inc, San Diego, Calif). Setting. - Seven nationwide university medical centers. Participants. - A total of 773 men (379 with prostate cancer, 394 with benign prostatic disease) 50 to 75 years of age with a palpably benign prostate gland, PSA level of 4.0 to 10.0 ng/mL, and histologically confirmed diagnosis. Main Outcome Measures. - A percentage of free PSA cutoff that maintained 95{\%} sensitivity for prostate cancer detection, and probability of cancer for individual patients. Results. - The percentage of free PSA may be used in 2 ways: as a single cutoff (ie, perform a biopsy for all patients at or below a cutoff of 25{\%} free PSA) or as an individual patient risk assessment (ie, base biopsy decisions on each patient's risk of cancer). The 25{\%} free PSA cutoff detected 95{\%} of cancers while avoiding 20{\%} of unnecessary biopsies. The cancers associated with greater than 25{\%} free PSA were more prevalent in older patients, and generally were less threatening in terms of tumor grade and volume. For individual patients, a lower percentage of free PSA was associated with a higher risk of cancer (range, 8{\%}-56{\%}). In the multivariate model used, the percentage of free PSA was an independent predictor of prostate cancer (odds ratio [OR], 3.2; 95{\%} confidence interval [CI], 2.5-4.1; P <.001) and contributed significantly more than age (OR, 1.2; 95{\%} CI, 0.92-1.55) or total PSA level (OR, 1.0; 95{\%} CI, 0.92-1.11) in this cohort of subjects with total PSA values between 4.0 and 10.0 ng/mL. Conclusions. - Use of the percentage of free PSA can reduce unnecessary biopsies in patients undergoing evaluation for prostate cancer, with a minimal loss in sensitivity in detecting cancer. A cutoff of 25{\%} or less free PSA is recommended for patients with PSA values between 4.0 and 10.0 ng/mL and a palpably benign gland, regardless of patient age or prostate size. To our knowledge, this study is the largest series to date evaluating the percentage of free PSA in a population representative of patients in whom the test would be used in clinical practice.",
author = "Catalona, {William J.} and Partin, {Alan Wayne} and Slawin, {Kevin M.} and Brawer, {Michael K.} and Flanigan, {Robert C.} and Anup Patel and Richie, {Jerome P.} and DeKernion, {Jean B.} and Patrick Walsh and Scardino, {Peter T.} and Lange, {Paul H.} and Subong, {Eric N P} and Parson, {Robert E.} and Gasior, {Gail H.} and Loveland, {Kathleen G.} and Southwick, {Paula C.}",
year = "1998",
month = "5",
day = "20",
doi = "10.1001/jama.279.19.1542",
language = "English (US)",
volume = "279",
pages = "1542--1547",
journal = "JAMA - Journal of the American Medical Association",
issn = "0098-7484",
publisher = "American Medical Association",
number = "19",

}

TY - JOUR

T1 - Use of the percentage of free prostate-specific antigen to enhance differentiation of prostate cancer from benign prostatic disease

T2 - A prospective multicenter clinical trial

AU - Catalona, William J.

AU - Partin, Alan Wayne

AU - Slawin, Kevin M.

AU - Brawer, Michael K.

AU - Flanigan, Robert C.

AU - Patel, Anup

AU - Richie, Jerome P.

AU - DeKernion, Jean B.

AU - Walsh, Patrick

AU - Scardino, Peter T.

AU - Lange, Paul H.

AU - Subong, Eric N P

AU - Parson, Robert E.

AU - Gasior, Gail H.

AU - Loveland, Kathleen G.

AU - Southwick, Paula C.

PY - 1998/5/20

Y1 - 1998/5/20

N2 - Context. - The percentage of free prostate-specific antigen (PSA) in serum has been shown to enhance the specificity of PSA testing for prostate cancer detection, but earlier studies provided only preliminary cutoffs for clinical use. Objective. - To develop risk assessment guidelines and a cutoff value for defining abnormal percentage of free PSA in a population of men to whom the test would be applied. Design. - Prospective blinded study using the Tandem PSA and free PSA assays (Hybritech Inc, San Diego, Calif). Setting. - Seven nationwide university medical centers. Participants. - A total of 773 men (379 with prostate cancer, 394 with benign prostatic disease) 50 to 75 years of age with a palpably benign prostate gland, PSA level of 4.0 to 10.0 ng/mL, and histologically confirmed diagnosis. Main Outcome Measures. - A percentage of free PSA cutoff that maintained 95% sensitivity for prostate cancer detection, and probability of cancer for individual patients. Results. - The percentage of free PSA may be used in 2 ways: as a single cutoff (ie, perform a biopsy for all patients at or below a cutoff of 25% free PSA) or as an individual patient risk assessment (ie, base biopsy decisions on each patient's risk of cancer). The 25% free PSA cutoff detected 95% of cancers while avoiding 20% of unnecessary biopsies. The cancers associated with greater than 25% free PSA were more prevalent in older patients, and generally were less threatening in terms of tumor grade and volume. For individual patients, a lower percentage of free PSA was associated with a higher risk of cancer (range, 8%-56%). In the multivariate model used, the percentage of free PSA was an independent predictor of prostate cancer (odds ratio [OR], 3.2; 95% confidence interval [CI], 2.5-4.1; P <.001) and contributed significantly more than age (OR, 1.2; 95% CI, 0.92-1.55) or total PSA level (OR, 1.0; 95% CI, 0.92-1.11) in this cohort of subjects with total PSA values between 4.0 and 10.0 ng/mL. Conclusions. - Use of the percentage of free PSA can reduce unnecessary biopsies in patients undergoing evaluation for prostate cancer, with a minimal loss in sensitivity in detecting cancer. A cutoff of 25% or less free PSA is recommended for patients with PSA values between 4.0 and 10.0 ng/mL and a palpably benign gland, regardless of patient age or prostate size. To our knowledge, this study is the largest series to date evaluating the percentage of free PSA in a population representative of patients in whom the test would be used in clinical practice.

AB - Context. - The percentage of free prostate-specific antigen (PSA) in serum has been shown to enhance the specificity of PSA testing for prostate cancer detection, but earlier studies provided only preliminary cutoffs for clinical use. Objective. - To develop risk assessment guidelines and a cutoff value for defining abnormal percentage of free PSA in a population of men to whom the test would be applied. Design. - Prospective blinded study using the Tandem PSA and free PSA assays (Hybritech Inc, San Diego, Calif). Setting. - Seven nationwide university medical centers. Participants. - A total of 773 men (379 with prostate cancer, 394 with benign prostatic disease) 50 to 75 years of age with a palpably benign prostate gland, PSA level of 4.0 to 10.0 ng/mL, and histologically confirmed diagnosis. Main Outcome Measures. - A percentage of free PSA cutoff that maintained 95% sensitivity for prostate cancer detection, and probability of cancer for individual patients. Results. - The percentage of free PSA may be used in 2 ways: as a single cutoff (ie, perform a biopsy for all patients at or below a cutoff of 25% free PSA) or as an individual patient risk assessment (ie, base biopsy decisions on each patient's risk of cancer). The 25% free PSA cutoff detected 95% of cancers while avoiding 20% of unnecessary biopsies. The cancers associated with greater than 25% free PSA were more prevalent in older patients, and generally were less threatening in terms of tumor grade and volume. For individual patients, a lower percentage of free PSA was associated with a higher risk of cancer (range, 8%-56%). In the multivariate model used, the percentage of free PSA was an independent predictor of prostate cancer (odds ratio [OR], 3.2; 95% confidence interval [CI], 2.5-4.1; P <.001) and contributed significantly more than age (OR, 1.2; 95% CI, 0.92-1.55) or total PSA level (OR, 1.0; 95% CI, 0.92-1.11) in this cohort of subjects with total PSA values between 4.0 and 10.0 ng/mL. Conclusions. - Use of the percentage of free PSA can reduce unnecessary biopsies in patients undergoing evaluation for prostate cancer, with a minimal loss in sensitivity in detecting cancer. A cutoff of 25% or less free PSA is recommended for patients with PSA values between 4.0 and 10.0 ng/mL and a palpably benign gland, regardless of patient age or prostate size. To our knowledge, this study is the largest series to date evaluating the percentage of free PSA in a population representative of patients in whom the test would be used in clinical practice.

UR - http://www.scopus.com/inward/record.url?scp=0032550630&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032550630&partnerID=8YFLogxK

U2 - 10.1001/jama.279.19.1542

DO - 10.1001/jama.279.19.1542

M3 - Article

VL - 279

SP - 1542

EP - 1547

JO - JAMA - Journal of the American Medical Association

JF - JAMA - Journal of the American Medical Association

SN - 0098-7484

IS - 19

ER -