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Prostate-Specific Antigen Velocity for Early Detection of Prostate Cancer: Result from a Large,Representative, Population-based Cohort
Authors:Andrew J. Vickers,Tineke Wolters,Caroline J. Savage,Angel M. Cronin,M. Frank O&rsquo  Brien,Kim Pettersson,Monique J. Roobol,Gunnar Aus,Peter T. Scardino,Jonas Hugosson,Fritz H. Schrö  der,Hans Lilja
Affiliation:1. Memorial Sloan-Kettering Cancer Center, New York, USA;2. Sahlgrenska University Hospital, Gothenburg, Sweden;3. Department of Biotechnology, University of Turku, Turku, Finland;4. Erasmus Medical Center, Rotterdam, The Netherlands;5. Lund University, University Hospital UMAS, Malmö, Sweden
Abstract:

Background

It has been suggested that changes in prostate-specific antigen (PSA) over time (ie, PSA velocity [PSAV]) aid prostate cancer detection. Some guidelines do incorporate PSAV cut points as an indication for biopsy.

Objective

To evaluate whether PSAV enhances prediction of biopsy outcome in a large, representative, population-based cohort.

Design, setting, and participants

There were 2742 screening-arm participants with PSA <3 ng/ml at initial screening in the European Randomized Study of Screening for Prostate Cancer in Rotterdam, Netherlands, or Göteborg, Sweden, and who were subsequently biopsied during rounds 2–6 due to elevated PSA.

Measurements

Total, free, and intact PSA and human kallikrein 2 were measured for 1–6 screening rounds at intervals of 2 or 4 yr. We created logistic regression models to predict prostate cancer based on age and PSA, with or without free-to-total PSA ratio (%fPSA). PSAV was added to each model and any enhancement in predictive accuracy assessed by area under the curve (AUC).

Results and limitations

PSAV led to small enhancements in predictive accuracy (AUC of 0.569 vs 0.531; 0.626 vs 0.609 if %fPSA was included), although not for high-grade disease. The enhancement depended on modeling a nonlinear relationship between PSAV and cancer. There was no benefit if we excluded men with higher velocities, which were associated with lower risk. These results apply to men in a screening program with elevated PSA; men with prior negative biopsy were not evaluated in this study.

Conclusions

In men with PSA of about ≥3 ng/ml, we found little justification for formal calculation of PSAV or for use of PSAV cut points to determine biopsy. Informal assessment of PSAV will likely aid clinical judgment, such as a sudden rise in PSA suggesting prostatitis, which could be further evaluated before biopsy.
Keywords:Cancer detection   Predictive models   Prostate biopsy   Prostate cancer   Prostate-specific antigen   PSA velocity
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