Originally published as JCO Early Release 10.1200/JCO.2008.18.1685 on December 8 2008

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Systematic Review of Pretreatment Prostate-Specific Antigen Velocity and Doubling Time As Predictors for Prostate Cancer

Andrew J. Vickers, Caroline Savage, M. Frank O'Brien, Hans Lilja

From the Departments of Epidemiology and Biostatistics, Surgery (Urology), and Clinical Laboratories, Memorial Sloan-Kettering Cancer Center, New York, NY

Corresponding author: Andrew J. Vickers, PhD, Department of Epidemiology and Biostatistics, Health Outcomes Research Group, Memorial Sloan-Kettering Cancer Center, Box 44, 1275 York Ave, New York, NY 10021; e-mail: vickersa{at}mskcc.org

Purpose Pretreatment prostate-specific antigen (PSA) dynamics (PSA velocity and PSA doubling time) are widely advocated as useful prognostic markers in prostate cancer. We aimed to assess the published evidence for the clinical utility of PSA dynamics in this population.

Methods We conducted a systematic review of studies published before March 2007 in which a PSA dynamic (velocity or doubling time) was calculated in patients before definitive treatment, a subsequent event (such as biopsy or recurrence) was ascertained, and the association between the two was analyzed. Our principal end point was the type of analysis reported, particularly whether the predictive accuracy of a statistical model that included both absolute PSA level and a PSA dynamic was compared with that of a model that included only PSA.

Results Eighty-seven articles were eligible for analysis. The most common end points were biopsy (42 articles), and either recurrence (14 articles) or metastases or death (14 articles) after definitive therapy. Although PSA dynamics were generally found to be associated with outcome, only one article compared predictive accuracy of models with and without a PSA dynamic: this reported that PSA velocity improved prediction slightly (from 0.81 to 0.83), but was subject to verification bias. No article used decision analytic methods to examine the clinical impact of PSA dynamics.

Conclusion There is little evidence that calculation of PSA velocity or doubling time in untreated patients provides predictive information beyond that provided by absolute PSA level alone. We see no justification for the use of PSA dynamics in clinical decision making before treatment in early-stage prostate cancer.

published online ahead of print at www.jco.org on December 8, 2008

Supported in part by a P50-CA92629 SPORE grant from the National Cancer Institute and by the Allbritton Fund and the Koch Foundation.

The funding bodies had no role in study design, data collection, data analysis, data interpretation, or writing of the report. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication.

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

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