Medline ® Abstracts for References 71-73

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.

OBJECTIVES: To study retrospectively whether the prostate-specific antigen (PSA) velocity, that is, the change in PSA level over time, might serve as a screening tool in this PSA range. It is estimated that 40% of detectable prostate cancers are present in men with a PSA level of 4.0 ng/mL or less. Digital rectal examination and/or transrectal ultrasonography have been used as screening tools at these low PSA levels, but this approach is not very efficient.

METHODS: The possible predictors (including PSA velocity) for biopsy outcome were studied using univariate and multivariate logistic regression analysis in 774 men who underwent biopsy between November 1997 and January 2002 in the second screening round of the European Randomised Study of Screening for Prostate Cancer (ERSPC). The clinical stage of the tumors was determined, and the Gleason scores of the biopsies were studied.

RESULTS: A total of 149 cancers were found (positive predictive value 19.2%). The odds ratio for the PSA velocity determined by univariate logistic regression analysis was 2.2 (95% confidence interval 0.7 to 6.9, P = 0.19) and was 0.73 (95% confidence interval 0.20 to 2.6, P = 0.64) by multivariate analysis. The distribution of the clinical stage of the detected tumors was 64.4% T1c, 32.2% T2, and 3.4% T3. The biopsy Gleason score was 6 in 84.5%, 7 in 14.2%, and 8 in 1.3%.

CONCLUSIONS: The number of cancers detected in this study and the distribution of clinical stage and biopsy Gleason score confirmed that a relatively large proportion of potentially curable cancers can be found in the low PSA ranges. The PSA velocity did not appear to be a useful screening tool for the identification of these cancers.

BACKGROUND: Prostate-specific antigen (PSA) testing is the primary method used to diagnose prostate cancer in the United States. Methods to integrate other risk factors associated with prostate cancer into individualized risk prediction are needed. We used prostate biopsy data from men who participated in the Prostate Cancer Prevention Trial (PCPT) to develop a predictive model of prostate cancer.

METHODS: We included 5519 men from the placebo group of the PCPT who underwent prostate biopsy, had at least one PSA measurement and a digital rectal examination (DRE) performed during the year before the biopsy, and had at least two PSA measurements performed during the 3 years before the prostate biopsy. Logistic regression was used to model the risk of prostate cancer and high-grade disease associated with age at biopsy, race, family history of prostate cancer, PSA level, PSA velocity, DRE result, and previous prostate biopsy. Risk equations were created from the estimated logistic regression models. All statistical tests were two-sided.

RESULTS: A total of 1211 (21.9%) menwere diagnosed with prostate cancer by prostate biopsy. Variables that predicted prostate cancer included higher PSA level, positive family history of prostate cancer, and abnormal DRE result, whereas a previous negative prostate biopsy was associated with reduced risk. Neither age at biopsy nor PSA velocity contributed independent prognostic information. Higher PSA level, abnormal DRE result, older age at biopsy, and African American race were predictive for high-grade disease (Gleason score>or =7) whereas a previous negative prostate biopsy reduced this risk.

CONCLUSIONS: This predictive model allows an individualized assessment of prostate cancer risk and risk of high-grade disease for men who undergo a prostate biopsy.