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Long-Term Prediction of Prostate Cancer: Prostate-Specific Antigen (PSA) Velocity Is Predictive but Does Not Improve the Predictive Accuracy of a Single PSA Measurement 15 Years or More Before Cancer Diagnosis in a Large, Representative, Unscreened Population

David Ulmert, Angel M. Serio, Matthew F. O'Brien, Charlotte Becker, James A. Eastham, Peter T. Scardino, Thomas Björk, Göran Berglund, Andrew J. Vickers, Hans Lilja

From the Departments of Surgery (Urology), Clinical Laboratories, Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY; and the Departments of Laboratory Medicine and Clinical Sciences in Malmö, Lund University, University Hospital UMAS, Malmö, Sweden

Corresponding author: Hans Lilja, MD, PhD, Department of Clinical Laboratories, Surgery (Urology), and Medicine (GU-Oncology), 1275 York Ave, Box 213, Memorial Sloan-Kettering Cancer Center, New York, NY 10021; e-mail: liljah{at}mskcc.org

Purpose: We tested whether total prostate-specific antigen velocity (tPSAv) improves accuracy of a model using PSA level to predict long-term risk of prostate cancer diagnosis.

Methods: During 1974 to 1986 in a preventive medicine study in Sweden, 5,722 men aged 50 gave two blood samples about 6 years apart. We measured free (fPSA) and total PSA (tPSA) in archived plasma samples from 4,907 participants. Prostate cancer was subsequently diagnosed in 443 (9%) men. Cox proportional hazards regression was used to evaluate tPSA and tPSAv as predictors of prostate cancer. Predictive accuracy was assessed by the concordance index.

Results: The median time from second blood draw to cancer diagnosis was 16 years; median follow-up for men without prostate cancer was 21 years. In univariate models, tPSA level at second assessment and tPSAv between first and second assessments were associated with prostate cancer (both P < .001). tPSAv was highly correlated with tPSA level (r = 0.93). Twenty-year probabilities of cancer for men at 50th, 90th, and 95th percentile of tPSA and tPSAv were 10.6%, 17.1%, and 21.2% for tPSA, and 9.1%, 11.8%, and 14.1% for tPSAv, respectively. The concordance index for tPSA level was 0.771. Adding tPSAv, fPSA, %fPSA or velocities of fPSA and %fPSA did not importantly increase accuracy of tPSA to predict prostate cancer. Results were unchanged if the analysis was restricted to patients with advanced cancer at diagnosis.

Conclusion: Although PSA velocity is significantly increased in men with prostate cancer up to two decades before diagnosis, it does not aid long-term prediction of prostate cancer.

This study was funded by P50-CA92629 SPORE from the National Cancer Institute, Swedish Cancer Society project No. 3555, Swedish Cancer Society Project No. 4715 European Union 6th Framework contract LSHC-CT-2004-503011 (P-Mark), and Fundación Federico SA.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

Related Editorial

• Prostate-Specific Antigen (PSA) and PSA Velocity: Competitors or Collaborators in the Prediction of Curable and Clinically Significant Prostate Cancer
  Anthony V. D'Amico
  JCO 2008 26: 823-824 [Full Text]

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