Author's Accepted Manuscript The Prostate Health Index (phi) Selectively Identifies Clinically-Significant Prostate Cancer Stacy Loeb , Martin G. Sanda , Dennis L. Broyles , Sanghyuk S. Shin , Chris H. Bangma , John T. Wei , Alan W. Partin , George G. Klee , Kevin M. Slawin , Leonard S. Marks , Ron H.N. van Schaik , Daniel W. Chan , Lori J. Sokoll , Amabelle B. Cruz , Isaac A. Mizrahi , William J. Catalona
PII: DOI: Reference:
S0022-5347(14)04900-3 10.1016/j.juro.2014.10.121 JURO 11997
To appear in: The Journal of Urology Accepted Date: 28 October 2014 Please cite this article as: Loeb S, Sanda MG, Broyles DL, Shin SS, Bangma CH, Wei JT, Partin AW, Klee GG, Slawin KM, Marks LS, van Schaik RHN, Chan DW, Sokoll LJ, Cruz AB, Mizrahi IA, Catalona WJ, The Prostate Health Index (phi®) Selectively Identifies Clinically-Significant Prostate Cancer, The Journal of Urology (2014), doi: 10.1016/j.juro.2014.10.121. DISCLAIMER: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our subscribers we are providing this early version of the article. The paper will be copy edited and typeset, and proof will be reviewed before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to The Journal pertain.
Embargo Policy All article content is under embargo until uncorrected proof of the article becomes available online. We will provide journalists and editors with full-text copies of the articles in question prior to the embargo date so that stories can be adequately researched and written. The standard embargo time is 12:01 AM ET on that date. Questions regarding embargo should be directed to [email protected].
ACCEPTED MANUSCRIPT 1 The Prostate Health Index (phi) Selectively Identifies Clinically-Significant Prostate Cancer Authors: Stacy Loeb, MD;* Martin G. Sanda, MD;† Dennis L. Broyles, MSHS;‡ Sanghyuk S. Shin, PhD;‡ Chris H. Bangma, MD, PhD;† John T. Wei, MD, MS; ‡ Alan W. Partin, MD, PhD;† George G.
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Klee, MD, PhD;‡ Kevin M. Slawin, MD;‡ Leonard S. Marks, MD;† Ron H.N. van Schaik, PhD;† Daniel W. Chan, PhD;† Lori J. Sokoll, PhD;‡ Amabelle B. Cruz, MSHA;‡ Isaac A. Mizrahi, PhD;‡ William J. Catalona, MD.‡
Author Affiliations: Department of Urology (Dr. Loeb), NYU Langone Medical Center, New York,
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New York; Department of Urology, Emory University and Emory Healthcare, (Dr. Sanda), Atlanta, Georgia; Department of Urology (Dr. Bangma) and Clinical Chemistry (Dr. van Schaik), Erasmus
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University Medical Center, Rotterdam, the Netherlands; Department of Urology, University of Michigan School of Medicine (Dr. Wei), Ann Arbor, Michigan; Department of Urology (Dr. Partin) and Pathology (Drs. Chan and Sokoll), Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Laboratory Medicine and Pathology, Mayo Clinic (Dr. Klee), Rochester, Minnesota; Vanguard Urologic Institute and Texas Prostate Center (Dr. Slawin), Houston, Texas; Department of Urology, University of California Los Angeles (Dr. Marks), Los Angeles, California; Beckman Coulter Incorporated (Dr. Mizrahi, Mr. Broyles, Dr. Shin and Ms. Cruz) Carlsbad, California; Department of
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Urology (Dr. Catalona), Northwestern University Feinberg School of Medicine, Chicago, Illinois.
Running Head: Prostate Health Index Identifies Significant Prostate Cancer
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Key Words: prostate health index, phi, marker, prostate cancer, screening
*Financial interest and/or other relationship with Sanofi. †Nothing to disclose.
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‡ Financial interest and/or other relationship with Beckman Coulter, Inc.
Corresponding Author: Stacy Loeb, MD MSc
550 1st Ave VZ30 (6th floor, #612) NY, NY 10016 Phone: 646-501-2559 Fax: 212-263-4549 Email: [email protected]
ACCEPTED MANUSCRIPT 2
Abstract Purpose: The Prostate Health Index (phi) is a new test combining total, free and [-2]proPSA into a single score. It was recently approved by the US FDA and is now commercially available in the US, Europe and
RI PT
Australia. Our objective was to investigate whether phi improves specificity for detecting clinicallysignificant prostate cancer and can help reduce prostate cancer over-diagnosis*.
Materials and Methods: From a multicenter prospective trial, we identified 658 men age ≥50 years with PSA levels from 4-10 ng/ml and normal digital rectal examination that underwent prostate biopsy. In this
SC
population, we compared the performance of PSA, % free PSA, [-2]proPSA, and phi to predict biopsy results and, specifically, the presence of clinically-significant prostate cancer using multiple criteria. Results: Phi was significantly higher in men with Gleason ≥7 and “Epstein-significant” cancer. On
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receiver operating characteristic analysis, phi had the highest AUC for overall cancer (AUC’s: phi 0.708, %fPSA 0.648, [-2]proPSA 0.550, and PSA 0.516), Gleason ≥7 (AUC’s: phi 0.707, %fPSA 0.661, [2]proPSA 0.558, PSA 0.551), and significant cancer (AUC’s: phi 0.698, %fPSA 0.654, [-2]proPSA 0.550, PSA 0.549). At the 90% sensitivity cutpoint for phi (a score 50% involvement of any core)12, and also Gleason ≥7 versus Gleason
PII: DOI: Reference:
S0022-5347(14)04900-3 10.1016/j.juro.2014.10.121 JURO 11997
To appear in: The Journal of Urology Accepted Date: 28 October 2014 Please cite this article as: Loeb S, Sanda MG, Broyles DL, Shin SS, Bangma CH, Wei JT, Partin AW, Klee GG, Slawin KM, Marks LS, van Schaik RHN, Chan DW, Sokoll LJ, Cruz AB, Mizrahi IA, Catalona WJ, The Prostate Health Index (phi®) Selectively Identifies Clinically-Significant Prostate Cancer, The Journal of Urology (2014), doi: 10.1016/j.juro.2014.10.121. DISCLAIMER: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our subscribers we are providing this early version of the article. The paper will be copy edited and typeset, and proof will be reviewed before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to The Journal pertain.
Embargo Policy All article content is under embargo until uncorrected proof of the article becomes available online. We will provide journalists and editors with full-text copies of the articles in question prior to the embargo date so that stories can be adequately researched and written. The standard embargo time is 12:01 AM ET on that date. Questions regarding embargo should be directed to [email protected].
ACCEPTED MANUSCRIPT 1 The Prostate Health Index (phi) Selectively Identifies Clinically-Significant Prostate Cancer Authors: Stacy Loeb, MD;* Martin G. Sanda, MD;† Dennis L. Broyles, MSHS;‡ Sanghyuk S. Shin, PhD;‡ Chris H. Bangma, MD, PhD;† John T. Wei, MD, MS; ‡ Alan W. Partin, MD, PhD;† George G.
RI PT
Klee, MD, PhD;‡ Kevin M. Slawin, MD;‡ Leonard S. Marks, MD;† Ron H.N. van Schaik, PhD;† Daniel W. Chan, PhD;† Lori J. Sokoll, PhD;‡ Amabelle B. Cruz, MSHA;‡ Isaac A. Mizrahi, PhD;‡ William J. Catalona, MD.‡
Author Affiliations: Department of Urology (Dr. Loeb), NYU Langone Medical Center, New York,
SC
New York; Department of Urology, Emory University and Emory Healthcare, (Dr. Sanda), Atlanta, Georgia; Department of Urology (Dr. Bangma) and Clinical Chemistry (Dr. van Schaik), Erasmus
M AN U
University Medical Center, Rotterdam, the Netherlands; Department of Urology, University of Michigan School of Medicine (Dr. Wei), Ann Arbor, Michigan; Department of Urology (Dr. Partin) and Pathology (Drs. Chan and Sokoll), Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Laboratory Medicine and Pathology, Mayo Clinic (Dr. Klee), Rochester, Minnesota; Vanguard Urologic Institute and Texas Prostate Center (Dr. Slawin), Houston, Texas; Department of Urology, University of California Los Angeles (Dr. Marks), Los Angeles, California; Beckman Coulter Incorporated (Dr. Mizrahi, Mr. Broyles, Dr. Shin and Ms. Cruz) Carlsbad, California; Department of
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Urology (Dr. Catalona), Northwestern University Feinberg School of Medicine, Chicago, Illinois.
Running Head: Prostate Health Index Identifies Significant Prostate Cancer
EP
Key Words: prostate health index, phi, marker, prostate cancer, screening
*Financial interest and/or other relationship with Sanofi. †Nothing to disclose.
AC C
‡ Financial interest and/or other relationship with Beckman Coulter, Inc.
Corresponding Author: Stacy Loeb, MD MSc
550 1st Ave VZ30 (6th floor, #612) NY, NY 10016 Phone: 646-501-2559 Fax: 212-263-4549 Email: [email protected]
ACCEPTED MANUSCRIPT 2
Abstract Purpose: The Prostate Health Index (phi) is a new test combining total, free and [-2]proPSA into a single score. It was recently approved by the US FDA and is now commercially available in the US, Europe and
RI PT
Australia. Our objective was to investigate whether phi improves specificity for detecting clinicallysignificant prostate cancer and can help reduce prostate cancer over-diagnosis*.
Materials and Methods: From a multicenter prospective trial, we identified 658 men age ≥50 years with PSA levels from 4-10 ng/ml and normal digital rectal examination that underwent prostate biopsy. In this
SC
population, we compared the performance of PSA, % free PSA, [-2]proPSA, and phi to predict biopsy results and, specifically, the presence of clinically-significant prostate cancer using multiple criteria. Results: Phi was significantly higher in men with Gleason ≥7 and “Epstein-significant” cancer. On
M AN U
receiver operating characteristic analysis, phi had the highest AUC for overall cancer (AUC’s: phi 0.708, %fPSA 0.648, [-2]proPSA 0.550, and PSA 0.516), Gleason ≥7 (AUC’s: phi 0.707, %fPSA 0.661, [2]proPSA 0.558, PSA 0.551), and significant cancer (AUC’s: phi 0.698, %fPSA 0.654, [-2]proPSA 0.550, PSA 0.549). At the 90% sensitivity cutpoint for phi (a score 50% involvement of any core)12, and also Gleason ≥7 versus Gleason
