Comparison of percent free PSA, PSA density, and age-specific PSA cutoffs for prostate cancer detection and staging.

OBJECTIVES: Various methods have been proposed to increase the specificity of prostate-specific antigen (PSA), including age-specific PSA reference ranges, PSA density (PSAD), and percent free PSA (%fPSA). In this multicenter study, we compared these methods for their utility in cancer detection and their ability to predict pathologic stage after radical prostatectomy in patients with clinically localized, Stage T1c cancer. METHODS: Seven hundred seventy-three men (379 with prostate cancer, 394 with benign prostatic disease), 50 to 75 years old, from seven medical centers were enrolled in this prospective blinded study. All subjects had a palpably benign prostate, PSA 4.0 to 10.0 ng/mL, and a histologically confirmed diagnosis. Hybritech's Tandem PSA and free PSA assays were used. RESULTS: %fPSA and age-specific PSA cutoffs enhanced PSA specificity for cancer detection, but %fPSA maintained significantly higher sensitivities. Age-specific PSA cutoffs missed 20% to 60% of cancers in men older than 60 years of age. %fPSA and PSAD performed equally well for detection (95% sensitivity) if cutoffs of 25% fPSA or 0.078 PSAD were used. The commonly used PSAD cutoff of 0.15 detected only 59% of cancers. %fPSA and PSAD also produced similar results for prediction of the post-radical prostatectomy pathologic stage. Patients with cancer with higher %fPSA values (greater than 15%) or lower PSAD values (0.15 or less) tended to have less aggressive disease. CONCLUSIONS: The results of this study demonstrated that cancer detection (sensitivity) is significantly higher with %fPSA than with age-specific PSA reference ranges. %fPSA and PSAD provide comparable results, suggesting that %fPSA may be used in place of PSAD for biopsy decisions and in algorithms for prediction of less aggressive tumors since the determination of %fPSA does not require ultrasound.

Percentage of free PSA in black versus white men for detection and staging of prostate cancer: a prospective multicenter clinical trial.

OBJECTIVES: In predominately white populations, measurement of the percentage of free prostate-specific antigen (%fPSA) has been shown to enhance the specificity of total PSA testing for prostate cancer while maintaining high sensitivity and to aid in prostate cancer staging. This study evaluated whether the %fPSA cutoff that maintained a 95% sensitivity in a white population yielded the same sensitivity and specificity in a black population and whether %fPSA was useful in predicting postoperative pathologic features in blacks. METHODS: We evaluated 647 white and 79 black men, prospectively enrolled at prostate cancer screening and surgical referral centers. Subjects were 50 to 75 years old with digital rectal examination findings that were not suspicious for prostate cancer and total PSA values between 4.0 and 10.0 ng/mL. All had undergone needle biopsy of the prostate. Hybritech's Tandem total and free PSA assays were used. RESULTS: Ninety-five percent sensitivity was attained with a %fPSA cutoff of 25% in both races. Use of this cutoff could have avoided unnecessary biopsies in 20% of white and 17% of black subjects (P = 0.69). In receiver operating characteristic (ROC) curve analysis, the area under the curve (AUC) for %fPSA was significantly higher than for total PSA in both blacks (0.76 versus 0.56, P <0.01) and whites (0.70 versus 0.54, P <0.001). In both races, higher %fPSA values indicated a lower risk of cancer and also predicted favorable pathologic features in radical prostatectomy specimens. CONCLUSIONS: A 25% fPSA cutoff detected 95% of cancers and reduced unnecessary biopsies in both races. Higher %fPSA values were associated with favorable postoperative histopathologic findings in both races.

Prediction of post-radical prostatectomy pathological outcome for stage T1c prostate cancer with percent free prostate specific antigen: a prospective multicenter clinical trial.

PURPOSE: Prostate specific antigen (PSA) exists in bound (complexed) and unbound (free) forms in serum. The percentage of free PSA enhances the specificity of PSA testing for prostate cancer detection. We evaluated the use of percent free PSA preoperatively to predict pathological stage. MATERIALS AND METHODS: A total of 379 men with prostate cancer and 394 with benign prostatic disease 50 to 75 years old were enrolled in this prospective study at 7 medical centers. All subjects had a palpably benign prostate gland, serum PSA 4.0 to 10.0 ng./ml. and a histologically confirmed diagnosis. The Hybritech Tandem PSA and free PSA assays were used. Of the 379 cancer patients 268 (71%) underwent radical prostatectomy. RESULTS: Higher percent free PSA levels were associated with more favorable histopathological findings in prostatectomy specimens. A value of 15% free PSA provided the greatest discrimination in predicting favorable pathological outcome. Organ confined cancer, Gleason sum less than 7 and small tumors (10% or less involvement of the prostate) were noted in 75% of patients with greater than 15% and only 34% with 15% or less free PSA (p<0.001). Multivariate logistic regression analysis revealed percent free PSA to be the strongest predictor of postoperative pathological outcome (odds ratio 2.25), followed by biopsy Gleason sum (2.06) and patient age (1.35). Total PSA was not predictive in this cohort but has been shown in prior studies to be predictive of outcome when a broader range of PSA values is evaluated. CONCLUSIONS: Percent free PSA may be used for risk assessment of the presence (diagnosis) and stage of prostate cancer in men with PSA between 4 and 10 ng./ml. Percent free PSA may be combined with PSA, digital rectal examination and biopsy findings to help predict postoperative pathological stage and grade, and may assist the patient and physician in making more informed treatment decisions.

Use of the percentage of free prostate-specific antigen to enhance differentiation of prostate cancer from benign prostatic disease: a prospective multicenter clinical trial.

CONTEXT: The percentage of free prostate-specific antigen (PSA) in serum has been shown to enhance the specificity of PSA testing for prostate cancer detection, but earlier studies provided only preliminary cutoffs for clinical use. OBJECTIVE: To develop risk assessment guidelines and a cutoff value for defining abnormal percentage of free PSA in a population of men to whom the test would be applied. DESIGN: Prospective blinded study using the Tandem PSA and free PSA assays (Hybritech Inc, San Diego, Calif). SETTING: Seven nationwide university medical centers. PARTICIPANTS: A total of 773 men (379 with prostate cancer, 394 with benign prostatic disease) 50 to 75 years of age with a palpably benign prostate gland, PSA level of 4.0 to 10.0 ng/mL, and histologically confirmed diagnosis. MAIN OUTCOME MEASURES: A percentage of free PSA cutoff that maintained 95% sensitivity for prostate cancer detection, and probability of cancer for individual patients. RESULTS: The percentage of free PSA may be used in 2 ways: as a single cut-off (ie, perform a biopsy for all patients at or below a cutoff of 25% free PSA) or as an individual patient risk assessment (ie, base biopsy decisions on each patient's risk of cancer). The 25% free PSA cutoff detected 95% of cancers while avoiding 20% of unnecessary biopsies. The cancers associated with greater than 25% free PSA were more prevalent in older patients, and generally were less threatening in terms of tumor grade and volume. For individual patients, a lower percentage of free PSA was associated with a higher risk of cancer (range, 8%-56%). In the multivariate model used, the percentage of free PSA was an independent predictor of prostate cancer (odds ratio [OR], 3.2; 95% confidence interval [CI], 2.5-4.1; P < .001) and contributed significantly more than age (OR, 1.2; 95% CI, 0.92-1.55) or total PSA level (OR, 1.0; 95% CI, 0.92-1.11) in this cohort of subjects with total PSA values between 4.0 and 10.0 ng/mL. CONCLUSIONS: Use of the percentage of free PSA can reduce unnecessary biopsies in patients undergoing evaluation for prostate cancer, with a minimal loss in sensitivity in detecting cancer. A cutoff of 25% or less free PSA is recommended for patients with PSA values between 4.0 and 10.0 ng/mL and a palpably benign gland, regardless of patient age or prostate size. To our knowledge, this study is the largest series to date evaluating the percentage of free PSA in a population representative of patients in whom the test would be used in clinical practice.

Analytical performance of the Tandem-R free PSA immunoassay measuring free prostate-specific antigen.

The analytical performance of the Tandem-R free PSA assay available from Hybritech Inc. was evaluated. Comparison of recoveries of purified free (unbound) prostate-specific antigen (PSA) diluted in female serum in the Tandem-R free PSA assay and the Tandem-R (total) PSA assay demonstrated a link in calibration between the assays and an accurate determination of percent free PSA. The cross-reactivity of the assay to purified PSA-alpha 1-antichymotrypsin was determined to be < 1%. The minimum-detectable concentration was < 0.05 microgram/L. The within-run and between-day CVs were < or = 5% for samples with > 0.3 microgram/L free PSA. Dilution and recovery showed no significant deviations from linearity across the assay range. The assay was insensitive to interference from blood components. The Tandem-R free PSA kit was shown to be an accurate, precise, and reliable assay for the measurement of free PSA.