Can urinary PCA3 supplement PSA in the early detection of prostate cancer?
OBJECTIVE
Given the limited sensitivity and specificity of prostate-specific antigen (PSA), its widespread use as a screening tool has raised concerns for the overdiagnosis of low-risk and the underdiagnosis of high-grade prostate cancer. To improve early-detection biopsy decisions, the National Cancer Institute conducted a prospective validation trial to assess the diagnostic performance of the prostate cancer antigen 3 (PCA3) urinary assay for the detection of prostate cancer among men screened with PSA.


METHODS
In all, 859 men (mean age, 62 years) from 11 centers scheduled for a diagnostic prostate biopsy between December 2009 and June 2011 were enrolled. The primary outcomes were to assess whether PCA3 could improve the positive predictive value (PPV) for an initial biopsy (at a score > 60) and the negative predictive value (NPV) for a repeat biopsy (at a score < 20).


RESULTS
For the detection of any cancer, PPV was 80% (95% CI, 72% to 86%) in the initial biopsy group, and NPV was 88% (95% CI, 81% to 93%) in the repeat biopsy group. The addition of PCA3 to individual risk estimation models (which included age, race/ethnicity, prior biopsy, PSA, and digital rectal examination) improved the stratification of cancer and of high-grade cancer.


CONCLUSIONS
These data independently support the role of PCA3 in reducing the burden of prostate biopsies among men undergoing a repeat prostate biopsy. For biopsy-naive patients, a high PCA3 score (> 60) significantly increases the probability that an initial prostate biopsy will identify cancer.
John T. Wei, University of Michigan, Ann Arbor, MI; Ziding Feng, Elissa Brown, Aron Y. Joon, Jackie Dahlgren, Fred Hutchinson Cancer Research Center; Daniel W. Lin, University of Washington, Seattle, WA; Alan W. Partin, Lori Sokoll, Daniel W. Chan, Johns Hopkins University, Baltimore; Jacob Kagan, Sudhir Srivastava, National Cancer Institute, Bethesda, MD; Ian Thompson, The University of Texas San Antonio, San Antonio; Yair Lotan, The University of Texas Southwestern Medical Center, Dallas, TX; Adam S. Kibel, Harvard University, Cambridge; Martin G. Sanda, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA; J. Erik Busby, University of South Carolina, Greenville, SC; Mohamed Bidair, San Diego Clinical Trials, San Diego, CA; Samir S. Taneja, New York University, New York, NY; and Rosalia Viterbo, Fox Chase Cancer Center, Philadelphia, PA. jtwei@umich.edu.
John T
JT
Wei
John T. Wei, University of Michigan, Ann Arbor, MI; Ziding Feng, Elissa Brown, Aron Y. Joon, Jackie Dahlgren, Fred Hutchinson Cancer Research Center; Daniel W. Lin, University of Washington, Seattle, WA; Alan W. Partin, Lori Sokoll, Daniel W. Chan, Johns Hopkins University, Baltimore; Jacob Kagan, Sudhir Srivastava, National Cancer Institute, Bethesda, MD; Ian Thompson, The University of Texas San Antonio, San Antonio; Yair Lotan, The University of Texas Southwestern Medical Center, Dallas, TX; Adam S. Kibel, Harvard University, Cambridge; Martin G. Sanda, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA; J. Erik Busby, University of South Carolina, Greenville, SC; Mohamed Bidair, San Diego Clinical Trials, San Diego, CA; Samir S. Taneja, New York University, New York, NY; and Rosalia Viterbo, Fox Chase Cancer Center, Philadelphia, PA.
Ziding
Z
Feng
John T. Wei, University of Michigan, Ann Arbor, MI; Ziding Feng, Elissa Brown, Aron Y. Joon, Jackie Dahlgren, Fred Hutchinson Cancer Research Center; Daniel W. Lin, University of Washington, Seattle, WA; Alan W. Partin, Lori Sokoll, Daniel W. Chan, Johns Hopkins University, Baltimore; Jacob Kagan, Sudhir Srivastava, National Cancer Institute, Bethesda, MD; Ian Thompson, The University of Texas San Antonio, San Antonio; Yair Lotan, The University of Texas Southwestern Medical Center, Dallas, TX; Adam S. Kibel, Harvard University, Cambridge; Martin G. Sanda, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA; J. Erik Busby, University of South Carolina, Greenville, SC; Mohamed Bidair, San Diego Clinical Trials, San Diego, CA; Samir S. Taneja, New York University, New York, NY; and Rosalia Viterbo, Fox Chase Cancer Center, Philadelphia, PA.
Alan W
AW
Partin
John T. Wei, University of Michigan, Ann Arbor, MI; Ziding Feng, Elissa Brown, Aron Y. Joon, Jackie Dahlgren, Fred Hutchinson Cancer Research Center; Daniel W. Lin, University of Washington, Seattle, WA; Alan W. Partin, Lori Sokoll, Daniel W. Chan, Johns Hopkins University, Baltimore; Jacob Kagan, Sudhir Srivastava, National Cancer Institute, Bethesda, MD; Ian Thompson, The University of Texas San Antonio, San Antonio; Yair Lotan, The University of Texas Southwestern Medical Center, Dallas, TX; Adam S. Kibel, Harvard University, Cambridge; Martin G. Sanda, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA; J. Erik Busby, University of South Carolina, Greenville, SC; Mohamed Bidair, San Diego Clinical Trials, San Diego, CA; Samir S. Taneja, New York University, New York, NY; and Rosalia Viterbo, Fox Chase Cancer Center, Philadelphia, PA.
Elissa
E
Brown
John T. Wei, University of Michigan, Ann Arbor, MI; Ziding Feng, Elissa Brown, Aron Y. Joon, Jackie Dahlgren, Fred Hutchinson Cancer Research Center; Daniel W. Lin, University of Washington, Seattle, WA; Alan W. Partin, Lori Sokoll, Daniel W. Chan, Johns Hopkins University, Baltimore; Jacob Kagan, Sudhir Srivastava, National Cancer Institute, Bethesda, MD; Ian Thompson, The University of Texas San Antonio, San Antonio; Yair Lotan, The University of Texas Southwestern Medical Center, Dallas, TX; Adam S. Kibel, Harvard University, Cambridge; Martin G. Sanda, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA; J. Erik Busby, University of South Carolina, Greenville, SC; Mohamed Bidair, San Diego Clinical Trials, San Diego, CA; Samir S. Taneja, New York University, New York, NY; and Rosalia Viterbo, Fox Chase Cancer Center, Philadelphia, PA.
Ian
I
Thompson
John T. Wei, University of Michigan, Ann Arbor, MI; Ziding Feng, Elissa Brown, Aron Y. Joon, Jackie Dahlgren, Fred Hutchinson Cancer Research Center; Daniel W. Lin, University of Washington, Seattle, WA; Alan W. Partin, Lori Sokoll, Daniel W. Chan, Johns Hopkins University, Baltimore; Jacob Kagan, Sudhir Srivastava, National Cancer Institute, Bethesda, MD; Ian Thompson, The University of Texas San Antonio, San Antonio; Yair Lotan, The University of Texas Southwestern Medical Center, Dallas, TX; Adam S. Kibel, Harvard University, Cambridge; Martin G. Sanda, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA; J. Erik Busby, University of South Carolina, Greenville, SC; Mohamed Bidair, San Diego Clinical Trials, San Diego, CA; Samir S. Taneja, New York University, New York, NY; and Rosalia Viterbo, Fox Chase Cancer Center, Philadelphia, PA.
Lori
L
Sokoll
John T. Wei, University of Michigan, Ann Arbor, MI; Ziding Feng, Elissa Brown, Aron Y. Joon, Jackie Dahlgren, Fred Hutchinson Cancer Research Center; Daniel W. Lin, University of Washington, Seattle, WA; Alan W. Partin, Lori Sokoll, Daniel W. Chan, Johns Hopkins University, Baltimore; Jacob Kagan, Sudhir Srivastava, National Cancer Institute, Bethesda, MD; Ian Thompson, The University of Texas San Antonio, San Antonio; Yair Lotan, The University of Texas Southwestern Medical Center, Dallas, TX; Adam S. Kibel, Harvard University, Cambridge; Martin G. Sanda, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA; J. Erik Busby, University of South Carolina, Greenville, SC; Mohamed Bidair, San Diego Clinical Trials, San Diego, CA; Samir S. Taneja, New York University, New York, NY; and Rosalia Viterbo, Fox Chase Cancer Center, Philadelphia, PA.
Daniel W
DW
Chan
John T. Wei, University of Michigan, Ann Arbor, MI; Ziding Feng, Elissa Brown, Aron Y. Joon, Jackie Dahlgren, Fred Hutchinson Cancer Research Center; Daniel W. Lin, University of Washington, Seattle, WA; Alan W. Partin, Lori Sokoll, Daniel W. Chan, Johns Hopkins University, Baltimore; Jacob Kagan, Sudhir Srivastava, National Cancer Institute, Bethesda, MD; Ian Thompson, The University of Texas San Antonio, San Antonio; Yair Lotan, The University of Texas Southwestern Medical Center, Dallas, TX; Adam S. Kibel, Harvard University, Cambridge; Martin G. Sanda, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA; J. Erik Busby, University of South Carolina, Greenville, SC; Mohamed Bidair, San Diego Clinical Trials, San Diego, CA; Samir S. Taneja, New York University, New York, NY; and Rosalia Viterbo, Fox Chase Cancer Center, Philadelphia, PA.
Yair
Y
Lotan
John T. Wei, University of Michigan, Ann Arbor, MI; Ziding Feng, Elissa Brown, Aron Y. Joon, Jackie Dahlgren, Fred Hutchinson Cancer Research Center; Daniel W. Lin, University of Washington, Seattle, WA; Alan W. Partin, Lori Sokoll, Daniel W. Chan, Johns Hopkins University, Baltimore; Jacob Kagan, Sudhir Srivastava, National Cancer Institute, Bethesda, MD; Ian Thompson, The University of Texas San Antonio, San Antonio; Yair Lotan, The University of Texas Southwestern Medical Center, Dallas, TX; Adam S. Kibel, Harvard University, Cambridge; Martin G. Sanda, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA; J. Erik Busby, University of South Carolina, Greenville, SC; Mohamed Bidair, San Diego Clinical Trials, San Diego, CA; Samir S. Taneja, New York University, New York, NY; and Rosalia Viterbo, Fox Chase Cancer Center, Philadelphia, PA.
Adam S
AS
Kibel
John T. Wei, University of Michigan, Ann Arbor, MI; Ziding Feng, Elissa Brown, Aron Y. Joon, Jackie Dahlgren, Fred Hutchinson Cancer Research Center; Daniel W. Lin, University of Washington, Seattle, WA; Alan W. Partin, Lori Sokoll, Daniel W. Chan, Johns Hopkins University, Baltimore; Jacob Kagan, Sudhir Srivastava, National Cancer Institute, Bethesda, MD; Ian Thompson, The University of Texas San Antonio, San Antonio; Yair Lotan, The University of Texas Southwestern Medical Center, Dallas, TX; Adam S. Kibel, Harvard University, Cambridge; Martin G. Sanda, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA; J. Erik Busby, University of South Carolina, Greenville, SC; Mohamed Bidair, San Diego Clinical Trials, San Diego, CA; Samir S. Taneja, New York University, New York, NY; and Rosalia Viterbo, Fox Chase Cancer Center, Philadelphia, PA.
J Erik
JE
Busby
John T. Wei, University of Michigan, Ann Arbor, MI; Ziding Feng, Elissa Brown, Aron Y. Joon, Jackie Dahlgren, Fred Hutchinson Cancer Research Center; Daniel W. Lin, University of Washington, Seattle, WA; Alan W. Partin, Lori Sokoll, Daniel W. Chan, Johns Hopkins University, Baltimore; Jacob Kagan, Sudhir Srivastava, National Cancer Institute, Bethesda, MD; Ian Thompson, The University of Texas San Antonio, San Antonio; Yair Lotan, The University of Texas Southwestern Medical Center, Dallas, TX; Adam S. Kibel, Harvard University, Cambridge; Martin G. Sanda, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA; J. Erik Busby, University of South Carolina, Greenville, SC; Mohamed Bidair, San Diego Clinical Trials, San Diego, CA; Samir S. Taneja, New York University, New York, NY; and Rosalia Viterbo, Fox Chase Cancer Center, Philadelphia, PA.
Mohamed
M
Bidair
John T. Wei, University of Michigan, Ann Arbor, MI; Ziding Feng, Elissa Brown, Aron Y. Joon, Jackie Dahlgren, Fred Hutchinson Cancer Research Center; Daniel W. Lin, University of Washington, Seattle, WA; Alan W. Partin, Lori Sokoll, Daniel W. Chan, Johns Hopkins University, Baltimore; Jacob Kagan, Sudhir Srivastava, National Cancer Institute, Bethesda, MD; Ian Thompson, The University of Texas San Antonio, San Antonio; Yair Lotan, The University of Texas Southwestern Medical Center, Dallas, TX; Adam S. Kibel, Harvard University, Cambridge; Martin G. Sanda, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA; J. Erik Busby, University of South Carolina, Greenville, SC; Mohamed Bidair, San Diego Clinical Trials, San Diego, CA; Samir S. Taneja, New York University, New York, NY; and Rosalia Viterbo, Fox Chase Cancer Center, Philadelphia, PA.
Daniel W
DW
Lin
John T. Wei, University of Michigan, Ann Arbor, MI; Ziding Feng, Elissa Brown, Aron Y. Joon, Jackie Dahlgren, Fred Hutchinson Cancer Research Center; Daniel W. Lin, University of Washington, Seattle, WA; Alan W. Partin, Lori Sokoll, Daniel W. Chan, Johns Hopkins University, Baltimore; Jacob Kagan, Sudhir Srivastava, National Cancer Institute, Bethesda, MD; Ian Thompson, The University of Texas San Antonio, San Antonio; Yair Lotan, The University of Texas Southwestern Medical Center, Dallas, TX; Adam S. Kibel, Harvard University, Cambridge; Martin G. Sanda, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA; J. Erik Busby, University of South Carolina, Greenville, SC; Mohamed Bidair, San Diego Clinical Trials, San Diego, CA; Samir S. Taneja, New York University, New York, NY; and Rosalia Viterbo, Fox Chase Cancer Center, Philadelphia, PA.
Samir S
SS
Taneja
John T. Wei, University of Michigan, Ann Arbor, MI; Ziding Feng, Elissa Brown, Aron Y. Joon, Jackie Dahlgren, Fred Hutchinson Cancer Research Center; Daniel W. Lin, University of Washington, Seattle, WA; Alan W. Partin, Lori Sokoll, Daniel W. Chan, Johns Hopkins University, Baltimore; Jacob Kagan, Sudhir Srivastava, National Cancer Institute, Bethesda, MD; Ian Thompson, The University of Texas San Antonio, San Antonio; Yair Lotan, The University of Texas Southwestern Medical Center, Dallas, TX; Adam S. Kibel, Harvard University, Cambridge; Martin G. Sanda, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA; J. Erik Busby, University of South Carolina, Greenville, SC; Mohamed Bidair, San Diego Clinical Trials, San Diego, CA; Samir S. Taneja, New York University, New York, NY; and Rosalia Viterbo, Fox Chase Cancer Center, Philadelphia, PA.
Rosalia
R
Viterbo
John T. Wei, University of Michigan, Ann Arbor, MI; Ziding Feng, Elissa Brown, Aron Y. Joon, Jackie Dahlgren, Fred Hutchinson Cancer Research Center; Daniel W. Lin, University of Washington, Seattle, WA; Alan W. Partin, Lori Sokoll, Daniel W. Chan, Johns Hopkins University, Baltimore; Jacob Kagan, Sudhir Srivastava, National Cancer Institute, Bethesda, MD; Ian Thompson, The University of Texas San Antonio, San Antonio; Yair Lotan, The University of Texas Southwestern Medical Center, Dallas, TX; Adam S. Kibel, Harvard University, Cambridge; Martin G. Sanda, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA; J. Erik Busby, University of South Carolina, Greenville, SC; Mohamed Bidair, San Diego Clinical Trials, San Diego, CA; Samir S. Taneja, New York University, New York, NY; and Rosalia Viterbo, Fox Chase Cancer Center, Philadelphia, PA.
Aron Y
AY
Joon
John T. Wei, University of Michigan, Ann Arbor, MI; Ziding Feng, Elissa Brown, Aron Y. Joon, Jackie Dahlgren, Fred Hutchinson Cancer Research Center; Daniel W. Lin, University of Washington, Seattle, WA; Alan W. Partin, Lori Sokoll, Daniel W. Chan, Johns Hopkins University, Baltimore; Jacob Kagan, Sudhir Srivastava, National Cancer Institute, Bethesda, MD; Ian Thompson, The University of Texas San Antonio, San Antonio; Yair Lotan, The University of Texas Southwestern Medical Center, Dallas, TX; Adam S. Kibel, Harvard University, Cambridge; Martin G. Sanda, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA; J. Erik Busby, University of South Carolina, Greenville, SC; Mohamed Bidair, San Diego Clinical Trials, San Diego, CA; Samir S. Taneja, New York University, New York, NY; and Rosalia Viterbo, Fox Chase Cancer Center, Philadelphia, PA.
Jackie
J
Dahlgren
John T. Wei, University of Michigan, Ann Arbor, MI; Ziding Feng, Elissa Brown, Aron Y. Joon, Jackie Dahlgren, Fred Hutchinson Cancer Research Center; Daniel W. Lin, University of Washington, Seattle, WA; Alan W. Partin, Lori Sokoll, Daniel W. Chan, Johns Hopkins University, Baltimore; Jacob Kagan, Sudhir Srivastava, National Cancer Institute, Bethesda, MD; Ian Thompson, The University of Texas San Antonio, San Antonio; Yair Lotan, The University of Texas Southwestern Medical Center, Dallas, TX; Adam S. Kibel, Harvard University, Cambridge; Martin G. Sanda, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA; J. Erik Busby, University of South Carolina, Greenville, SC; Mohamed Bidair, San Diego Clinical Trials, San Diego, CA; Samir S. Taneja, New York University, New York, NY; and Rosalia Viterbo, Fox Chase Cancer Center, Philadelphia, PA.
Jacob
J
Kagan
John T. Wei, University of Michigan, Ann Arbor, MI; Ziding Feng, Elissa Brown, Aron Y. Joon, Jackie Dahlgren, Fred Hutchinson Cancer Research Center; Daniel W. Lin, University of Washington, Seattle, WA; Alan W. Partin, Lori Sokoll, Daniel W. Chan, Johns Hopkins University, Baltimore; Jacob Kagan, Sudhir Srivastava, National Cancer Institute, Bethesda, MD; Ian Thompson, The University of Texas San Antonio, San Antonio; Yair Lotan, The University of Texas Southwestern Medical Center, Dallas, TX; Adam S. Kibel, Harvard University, Cambridge; Martin G. Sanda, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA; J. Erik Busby, University of South Carolina, Greenville, SC; Mohamed Bidair, San Diego Clinical Trials, San Diego, CA; Samir S. Taneja, New York University, New York, NY; and Rosalia Viterbo, Fox Chase Cancer Center, Philadelphia, PA.
Sudhir
S
Srivastava
John T. Wei, University of Michigan, Ann Arbor, MI; Ziding Feng, Elissa Brown, Aron Y. Joon, Jackie Dahlgren, Fred Hutchinson Cancer Research Center; Daniel W. Lin, University of Washington, Seattle, WA; Alan W. Partin, Lori Sokoll, Daniel W. Chan, Johns Hopkins University, Baltimore; Jacob Kagan, Sudhir Srivastava, National Cancer Institute, Bethesda, MD; Ian Thompson, The University of Texas San Antonio, San Antonio; Yair Lotan, The University of Texas Southwestern Medical Center, Dallas, TX; Adam S. Kibel, Harvard University, Cambridge; Martin G. Sanda, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA; J. Erik Busby, University of South Carolina, Greenville, SC; Mohamed Bidair, San Diego Clinical Trials, San Diego, CA; Samir S. Taneja, New York University, New York, NY; and Rosalia Viterbo, Fox Chase Cancer Center, Philadelphia, PA.
Martin G
MG
Sanda
D000368:Aged; D000951:Antigens, Neoplasm / Q000652:urine*; D001706:Biopsy; D055088:Early Detection of Cancer; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011467:Prostate / Q000473:pathology; D017430:Prostate-Specific Antigen / Q000097:blood*; D011471:Prostatic Neoplasms / Q000175:diagnosis*; D018570:Risk Assessment
D000951:Antigens, Neoplasm; C479341:prostate cancer antigen 3, human; D017430:Prostate-Specific Antigen