Using the Free-to-total Prostate-specific Antigen Ratio to Detect Prostate Cancer in Men with Nonspecific Elevations of Prostate-specific Antigen Levels

Authors

  • Richard M. Hoffman MD, MPH,

    1. Medicine Service, Albuquerque Department of Veterans Affairs Medical Center
    2. University of New Mexico School of Medicine, Albuquerque, NM Department of Medicine, The University of Vermont, Burlington, Vt
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  • David L. Clanon MD,

    1. Medicine Service, Albuquerque Department of Veterans Affairs Medical Center
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  • Benjamin Littenberg MD,

  • Joseph J. Frank PhD,

    1. Department of Medical Education and Research, Good Samaritan Regional Medical Center, Phoenix, Ariz Laboratory Sciences of Arizona, Phoenix, Ariz
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  • John C. Peirce MD, MA, MS

    1. Department of Medical Education and Research, Good Samaritan Regional Medical Center, Phoenix, Ariz Laboratory Sciences of Arizona, Phoenix, Ariz
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  • This work was presented in part at the Society of General Internal Medicine annual meeting, Washington, DC, May 1997.

Address correspondence and reprint requests to Dr. Hoffman: Albuquerque VA Medical Center, 111GIM, 1501 San Pedro Dr. SE, Albuquerque, NM 87108 (e-mail: rhoffman@unm.edu).

Abstract

BACKGROUND: Prostate-specific antigen (PSA) levels between 4.0 to 10.0 ng/ml have poor specificity in prostate cancer screening, leading to unnecessary biopsies.

OBJECTIVE: To determine whether the free-to-total PSA ratio (F/T PSA) improved the diagnostic accuracy of these nonspecific PSA levels.

MEASUREMENTS AND MAIN RESULTS:Medline was searched from 1986 to 1997. Additional studies were identified from article bibliographies and by searching urology journals. Two investigators independently identified English-language studies providing F/T PSA ratio test-operating characteristics data on ≥10 cancer patients with PSA values between 2.0 and 10.0 ng/ml. Twenty-one of 90 retrieved studies met selection criteria. Two investigators independently extracted data on methodology and diagnostic performance. Investigator-selected cut points for the optimal F/T PSA ratio had a median likelihood ratio of 1.76 (interquartile range, 1.40 to 2.11) for a positive test and 0.27 (0.20 to 0.40) for a negative test. Assuming a 25% pretest probability of cancer, the posttest probabilities were 37% following a positive test and 8% following a negative test. The summary receiver operating characteristic curve showed that maintaining test sensitivity above 90% was associated with false positive rates of 60% to 90%. Methodologic problems limited the validity and generalizability of the literature.

CONCLUSIONS: A negative test reduced the posttest probability of cancer to approximately 10%. However, patients may find that this probability is not low enough to avoid undergoing prostate biopsy. The optimal F/T PSA ratio cut point and precise estimates for test specificity still need to be determined.

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