Sensitivity For Prostate Cancer Detection Research Articles

The Predictive Value of Percent Free PSA Using a Chiron Assay in Patients with a PSA of 4-10 ng/ml and a Previous Negative Prostatic Biopsy

Aims : This study aims to: determine a serum percent free prostate specific antigen (% fPSA) cut-off using the Chiron assay which increases the specificity of PSA testing without detriment to the cancer detection rate. determine the predictive value of % fPSA using the Chiron assay for detecting prostate cancer on repeat prostatic biopsies. Patient and Methods : A retrospective review of transrectal ultrasound (TRUS) and prostatic biopsies performed between August 1997 and October 1998 was carried out. Eighty four consecutive patients with a serum total PSA (tPSA) of 4.1-10.0 ng/ml, a benign feeling prostate gland on digital rectal examination (DRE) and a previous prostatic biopsy negative for prostate cancer were included in the study. Measurements for tPSA and % fPSA were performed with the Chiron ACS tPSA and Chiron ACS 180 fPSA polyclonal antibody immunoassay, respectively. Results : The final cohort consisted of 53 patients, and, 8 of the 53 (15%) patients had prostate cancer diagnosed on repeat prostatic biopsies. The mean % fPSA was significantly lower in patients with cancer (14%) compared to patients without cancer (22%). Using a 20% cut-off for % fPSA, 33% of the negative biopsies could be avoided with a 95% sensitivity for detection of prostate cancer. Conclusion : Percent free PSA is a reliable predictor for detection of prostate cancer on repeat prostatic biopsies. However, individual immunoassays vary in the cut-off of % fPSA needed to provide acceptable sensitivity for prostate cancer detection and need to be clinically validated.

Diagnostic significance of digital rectal examination and transrectal ultrasonography in men with prostate-specific antigen levels of 4 ng/mL or less

Objectives. To investigate the usefulness of digital rectal examination (DRE) and transrectal ultrasonography (TRUS) for prostate cancer diagnosis and to propose a diagnostic algorithm for individual-based cancer screening in subjects with prostate-specific antigen (PSA) levels of 4.0 ng/mL or less. Methods. Between January 1992 and March 2000, 129 subjects with PSA levels of 4.0 or less and abnormal findings on DRE or TRUS underwent prostate biopsy. The subjects were divided into four groups according to the PSA range: 0 to 0.9 ng/mL, 1.0 to 1.9 ng/mL, 2.0 to 2.9 ng/mL, and 3.0 to 4.0 ng/mL. The reliability of the DRE and TRUS and the clinicopathologic features of prostate cancer were investigated among these four groups. Results. Of the 129 subjects, 17 (13.2%) patients with prostate cancer were diagnosed. The detection rate was 2.2% (1 of 45), 0% (0 of 27), 20.6% (7 of 34), and 39.1% (9 of 23) in subjects with PSA levels of less than 1.0 ng/mL, 1.0 to 1.9 ng/mL, 2.0 to 2.9 ng/mL, and 3.0 to 4.0 ng/mL, respectively. The proportion of patients with Stage II, III, and IV was 58.8%, 41.2%, and 0%, respectively. The percentage with Gleason scores of 8 to 10 was 17.6%. The detection rate of abnormal findings on DRE and TRUS was 14.4% (13 of 90) and 9.5% (7 of 74), respectively. Adding TRUS to DRE in the screening program of subjects with PSA levels of 2.0 to 4.0 ng/mL, increased the detection rate of prostate cancer to 30.8% (4 of 13). Conclusions. Routine prostate biopsy should not be undertaken except for highly suspicious DRE findings in subjects with PSA levels less than 2.0 ng/mL. The additional use of TRUS in subjects with PSA levels of 2.0 to 4.0 ng/mL would improve the sensitivity of prostate cancer detection. The diagnostic algorithm proposed in the present study is useful as a screening method for prostate cancer in subjects with PSA levels of 4.0 ng/mL or less.

New serum tests for the diagnosis of prostate cancer.

Prostate-specific antigen (PSA) has had a profound impact on the early diagnosis, treatment and follow-up of prostate cancer, the most common malignancy in men. However, it is not only a marker for prostate cancer but is also often expressed in benign conditions such as benign prostatic hyperplasia, prostatitis and other inflammatory disorders. For early detection of prostate cancer, limitations of the use of PSA become obvious; its widespread use has led to extensive expensive and often unnecessary diagnostic procedures associated with significant morbidity. New serum tests derived from total PSA may play a key role in enhancing the accuracy of prostate cancer diagnosis. The ratio of free to total PSA improves specificity while maintaining a high sensitivity for prostate cancer detection for men with a total PSA of 2.5-10 ng/ml who also have a normal digital rectal examination. Human glandular kallikrein 2 also has the potential to be a valuable tool in combination with both total and free PSA for the early diagnosis of prostate cancer. However, the optimal clinical use of human glandular kallikrein 2 still remains to be clarified. Complex PSA seems to be a reliable tool and equivalent alternative to total PSA to improve specificity at high sensitivity levels in men with suspected prostate cancer, mainly for PSA levels below 4 ng/ml. Several newly discovered isoforms of free PSA (bPSA, [-2]pPSA and inactive intact PSA) may also impact the early detection of prostate cancer, with encouraging preliminary results that warrant further clinical investigation. (c) 2001 Prous Science. All rights reserved.

PSA, PSA density, PSA density of transition zone, free/total PSA ratio, and PSA velocity for early detection of prostate cancer in men with serum PSA 2.5 to 4.0 ng/mL

Objectives. To enhance the specificity of prostate cancer (PCa) detection and reduce unnecessary biopsies in men with prostate-specific antigen (PSA) levels of 2.5 to 4.0 ng/mL, we prospectively evaluated various PSA-based diagnostic parameters. Methods. This study included 273 consecutive men with serum PSA of 2.5 to 4.0 ng/mL referred for early PCa detection or lower urinary tract symptoms. All men underwent prostate ultrasound and sextant biopsy with two additional transition zone (TZ) biopsies. If the first biopsies were negative, repeated biopsies were performed at 6 weeks. Total PSA, PSA density (PSAD), PSA density of the transition zone (PSA-TZ), free/total PSA ratio (f/t PSA), and PSA velocity (PSAV) were determined, and the sensitivity, specificity, and predictive values of these various parameters were calculated. Results. Of 273 patients, 207 had histologically confirmed benign prostatic hyperplasia (BPH) and 66 had PCa. f/t PSA and PSA-TZ were the most powerful predictors of PCa, followed by PSA, PSAD, and PSAV. Areas under the receiver operating characteristic curves for f/t PSA and PSA-TZ were 74.9% and 70.1%, respectively. With a 95% sensitivity for PCa detection, an f/t PSA cutoff of 41% and a PSA-TZ cutoff of 0.095 would result in the lowest number of unnecessary biopsies (29.3% and 17.2% specificity for f/t PSA and PSA-TZ, respectively) compared with all other PSA-related parameters evaluated. Conclusions. Compared with standard total PSA assays, f/t PSA and PSA-TZ significantly enhance the sensitivity and specificity of PCa detection in a referral patient population with a total PSA of 2.5 to 4.0 ng/mL.

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 cutoff (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.

PROSTATE SPECIFIC ANTIGEN DENSITY OF THE TRANSITION ZONE FOR EARLY DETECTION OF PROSTATE CANCER

Purpose We compare the ability of several prostate specific antigen (PSA) parameters, including PSA density of the whole prostate and of the transition zone, percent free PSA and PSA velocity, to enhance the specificity for prostate cancer detection and to reduce unnecessary biopsies in men with serum PSA levels of 4 to 10.0 ng./ml. Materials and Methods This prospective study included 559 consecutive men referred for early prostate detection or lower urinary tract symptoms who had a serum PSA of 4.0 to 10.0 ng./ml. All men underwent prostatic ultrasonography and sextant biopsy with 2 additional transition zone biopsies. Specific biopsies of abnormal findings on digital rectal examination were also performed. In all cases if first biopsies were negative an additional set of biopsies was performed within 6 weeks. The ability of PSA density, PSA transition zone, PSA velocity and percent free PSA to improve the power of PSA in the detection of prostate cancer was evaluated with univariate and multivariate analyses as well as receiver operating characteristics (ROC) curves. Results Of 559 patients 342 had histologically confirmed benign prostatic hyperplasia and 217 had prostate cancer. Mean serum PSA, PSA velocity, PSA density and PSA transition zone were statistically higher (p <0.018, p <0.037, p <0.0001 and p <0.0001, respectively) and percent free PSA was statistically lower (p <0.0001) in patients with prostate cancer than in those with benign disease. Multivariate analysis and ROC curves showed that PSA transition zone and percent free PSA were the most powerful and highly significant predictors of prostate cancer. Areas under the ROC curve for PSA transition zone and percent free PSA were 0.827 and 0.778, respectively (p = 0.01 McNemar test). Combination of free-to-total PSA with PSA transition zone significantly increased the area under the ROC curve compared to PSA transition zone alone (p = 0.020). With a 95% sensitivity for prostate cancer detection a PSA transition zone cutoff of 0.25 ng./ml./cc would result in the lowest number of unnecessary biopsies (47% PSA transition zone specificity) compared to all other PSA parameters. However, total prostate volume (greater than 30 cc in 422 men or less than 30 cc in 137) was an important factor in predicting the statistical performance of PSA transition zone. In fact, PSA transition zone did not outperform free percent PSA in sensitivity and specificity when the entire prostate gland volume was less than 30 cc (p = 0.094 McNemar test). Conclusions PSA density of the transition zone enhances the specificity of serum PSA for prostate cancer detection in referred patients with a serum PSA of 4.0 to 10.0 ng./ml. compared to other PSA parameters currently available. While PSA transition zone was more effective in prostates greater than 30 cc and percent free PSA was more effective in prostates less than 30 cc, the combination of percent free PSA with PSA transition zone further increased prostate cancer prediction.

Clinical evaluation of serum prostate-specific antigen-alpha1-antichymotrypsin complex values in diagnosis of prostate cancer: a cooperative study.

We studied the clinical significance of serum prostate-specific antigen bound to alpha1-antichymotrypsin (PSA-ACT) values determined with a newly developed enzyme immunoassay. Serum PSA-ACT values were determined in a total of 652 sera. Clinical utility for the diagnosis of prostate cancer was compared to that of Tandem-R PSA and gamma-seminoprotein (gamma-Sm). The new enzyme immunoassay is based on the use of the Stanford reference as an international standard for PSA assays. Serum PSA-ACT values ranged from less than 0.10 to 1.4 ng/mL in healthy males (n = 100) while values in patients with benign prostatic hyperplasia (n = 155) averaged 3.4 +/- 3.8 ng/mL (mean +/- SD). In patients with prostate cancer, serum PSA-ACT values increased significantly with progression of the clinical stage and there were statistically significant differences between benign prostatic hyperplasia and each stage of prostate cancer except for stage A. Using BPH levels as controls (4.8 ng/mL for PSA-ACT, 7.2 ng/mL for PSA, 3.8 ng/mL for gamma-Sm, and 2.4 ng/mL for the complexed/free PSA ratio of PSA-ACT/gamma-Sm), specificity was 80%. The sensitivity of prostate cancer detection was 79% for PSA-ACT, 77% for PSA, 57% for gamma-Sm, and 46% for the ratio between PSA-ACT/gamma-Sm. Although the determination of serum PSA-ACT showed essentially the same utility as that of PSA for the diagnosis of prostate cancer, PSA-ACT may allow prediction of the clinical stage. The PSA-ACT assay may therefore replace PSA in the detection of prostate cancer.