Prostate-specific antigen velocity for early detection of prostate cancer: result from a large, representative, population-based cohort

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.

Fig. 1

[en] Flow of participants through the study.

Fig. 2

[en] Predicted probability of a positive biopsy with increasing prostate-specific antigen (PSA) velocity, controlling for PSA. Probabilities are for a subject with a PSA level of 4.3 ng/ml, which was the mean PSA for the cohort. Black line: modeled with nonlinear terms; gray line: modeled with only a linear term; dashed lines: 95% confidence intervals.

Fig. 3

[en] Decision curve analysis. The curves show the clinical benefit for basing biopsy decisions on the models with total prostate-specific antigen (PSA) plus age (dotted line), total PSA plus age plus free-to-total PSA ratio (%fPSA; dashed line), and total PSA plus age plus %fPSA plus PSA velocity (thin solid line); biopsy all men (thick grey line); and biopsy no man (thick black line).

Fig. 4

[en] Decision curve analysis for men with prostate-specific antigen (PSA) velocity <0.75 ng/ml per year. Total PSA plus age (dotted line), total PSA plus age plus free-to-total PSA ratio (%fPSA; dashed line), total PSA plus age plus %fPSA plus PSA velocity (thin solid line), biopsy all men (thick grey line), biopsy no man (thick black line).