Percent Free Prostate-specific Antigen Levels Research Articles

Individualized prostate-specific antigen threshold values to avoid overdiagnosis of prostate cancer and reduce unnecessary biopsy in elderly men.

To individualize prostate-specific antigen threshold values to avoid overdiagnosis of prostate cancer and reduce unnecessary biopsy in elderly men. A total of 406 men aged over 70 years old with prostate-specific antigen levels between 4.0 and 20.0 ng/ml, normal digital rectal examination results and diagnosed by transrectal needle biopsy were retrospectively analyzed. The patients were divided into a no/favorable-risk cancer group or an unfavorable-risk cancer group based on their Gleason score and the number of positive cores. Prostate-specific antigen levels, percent free prostate-specific antigen level, prostate transition zone volume and the number of previous biopsies were used to discriminate between the two groups. The optimal individualized prostate-specific antigen threshold values based on the other variables that gave a sensitivity of 95% for the detection of unfavorable-risk cancer were calculated using a boosting method for maximizing the area under the receiver operating characteristic curve. A total of 66 men had favorable-risk cancer, and 139 had unfavorable-risk cancer. The area under the receiver operating characteristic curve of the combination model determined by the boosting method for maximizing the area under the receiver operating characteristic curve was 0.852. The sensitivity and specificity of the threshold values for the detection of unfavorable-risk cancer were 95 and 36%, respectively. By using the threshold values, 100 (25%) of the subjects with no/favorable-risk cancer could have avoided undergoing biopsies, with a <5% risk of missing the detection of unfavorable-risk cancer. These individualized prostate-specific antigen threshold values may be useful for determining an indication of prostate biopsy for elderly men to avoid overdiagnosis of prostate cancer and reduce unnecessary biopsy.

Association between percent-free prostate-specific antigen and glomerular filtration rate in transrectal ultrasound-guided biopsy-proven patients with prostate-specific antigen levels ranging from 4 to 10 ng/ml

The aim of this study was to investigate the relationship between percent-free prostate-specific antigen (PSA) and estimated glomerular filtration rate (GFR) in men whose PSA level was 4-10 ng/ml with biopsy-proven prostate status. Between 2004 and 2010, the medical records of 495 cases (404 cases without prostate cancer and 91 cases with prostate cancer) who underwent prostate biopsy were reviewed and their GFR was calculated using the Cockcroft-Gault equation, adjusted for body surface area. Correlation and multivariate regression analyses were conducted among percent-free PSA, body mass index, prostate size, and GFR in patients with and without prostate cancer, respectively. The mean patient age was 64.6 years, and the median PSA and free PSA were 5.64 and 0.87 ng/ml. The mean GFR was 61.02 mL/min/1.73 m2, and mean percent-free PSA was 18.9%. Correlation analysis showed that percent-free PSA was correlated with GFR, age, and prostate size in the non-cancer cohort and correlated with only prostate size in the cancer cohort. Multivariate regression analysis showed that percent-free PSA was influenced by GFR (p < 0.001) and prostate size (p < 0.001) independently in the non-cancer cohort, while only by prostate size (p = 0.008) in the cancer cohort. Percent-free PSA has a negative relationship with GFR in the benign prostate group, while it does not in the prostate cancer group. Screening with current cutoff value of percent-free PSA can be applied to the patients with impaired renal function.

Effect of Flexible Cystoscopy on Serum Prostate-Specific Antigen Values

To determine the effect of flexible cystoscopy on the total, free, and percent-free prostate-specific antigen (PSA) values in male volunteers. Flexible cystoscopy is the standard method of evaluation of the bladder and urethra. PSA measurement is currently used in conjunction with the digital rectal examination to detect and guide management of prostate cancer. Thus, we must understand the effect of flexible cystoscopy on serum PSA levels. Healthy men who were undergoing flexible cystoscopy and provided informed consent were enrolled in the study. The volunteers had blood taken for PSA measurement before cystoscopy and 1 and 24 hours after. The mean PSA values were compared using the paired t test. A total of 40 volunteers (age 22-82 years) enrolled in the study. Statistically significant increases in the total, free, and percent-free PSA values were noted at 1 and 24 hours after cystoscopy. The differences of 0.113 and 0.112 ng/mL (P < .05) in the mean total PSA level at 1 and 24 hours after cystoscopy were not clinically significant. The interassay variability was 0.053 ng/mL, with a standard deviation of 0.150 ng/mL. The standard deviation of 0150 ng/mL was greater than the 0.113- and 0.112-ng/mL differences seen in the total PSA values at 1 and 24 hours after cystoscopy. Statistically significant differences were noted in the total, free, and percent-free PSA levels before and after cystoscopy. Although these small differences achieved statistical significance, none were clinically significant. We have concluded that the serum PSA values are not affected by diagnostic flexible cystoscopy.

The Influence of Prostate Volume on the Serum Prostate-specific Antigen Levels and the Percentage of the Free Prostate-specific Antigen Levels during Finasteride Medication

Purpose: Little is known about the effect of the prostate volume on the free prostate-specific antigen (PSA) level and the percent of the free PSA level with administering finasteride medication. We studied the effect of finasteride therapy on the levels of serum PSA, the free PSA and the percentage of free PSA according to the prostate volume. Materials and Methods: Patients with lower urinary tract symptoms (LUTS) and benign prostatic hyperplasia (BPH) and who were over 50 years old were treated with finasteride 5mg for 6 months. Male patients with a PSA level between 3.5ng/ml and 15ng/ml were included and these patients were biopsied. α-blockers were prescribed to treat them for LUTS. The serum levels of the total PSA and free PSA were measured at baseline and after 6 months. We analyzed the changes of PSA and fre-PSA before and after finasteride administration. We also analyzed the patients' changes based on the prostate volume. Results: The analysis included 44 patients with a mean age of 71.7 years, a baseline prostate volume of 56.0cc and a baseline total PSA level of 6.74ng/ml. The total PSA and free PSA levels declined from 6.74ng/ml and 2.57ng/ml at baseline to 3.83ng/ml and 1.45ng/ml after 6 months of treatment, respectively (p<0.05). The mean percent free PSA was not significantly altered by finasteride treatment. Those patients with a small prostate volume showed larger decrements in the PSA and free PSA than did the patients with a large prostate volume, but the prostate volume at baseline did not affect the percent free PSA levels. Conclusions: It is debatable that the application of the 'double's rule' without considering the volume of the prostate is appropriate for the treatment of patients who are taking finasteride medication. (Korean J Urol 2007;48:1242-1246) 󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏

Absence of Lower Urinary Tract Symptoms Is an Independent Predictor for Cancer at Prostate Biopsy, but Prostate-Specific Antigen Is Not: Results from a Prospective Series of 569 Patients

PurposeProstate needle biopsy (PNB) is the definitive method for the diagnosis of prostate cancer. Our objective was to evaluate prebiopsy parameters, including lower urinary tract symptoms, that may be predictive of positive biopsy. Patients and MethodsWe performed a prospective review of 569 consecutive men who underwent transrectal ultrasound (TRUS)–guided PNB. The prebiopsy variables recorded included age, prostate-specific antigen (PSA) levels, prostate volume (PV), percent free PSA levels, suspicious digital rectal examination (DRE) findings, TRUS-detected lesions, race, and American Urologic Association Symptom Score (AUASS). ResultsLow AUASS, PV, patient age, and abnormal TRUS findings were independent predictors of positive PNB results (P < 0.05). In patients with PSA levels between 4 and 10 ng/mL, the positive predictive value of a low AUASS (< 8) in predicting a positive PNB result is 68.7%. When race was considered (black vs. white), univariate analysis (UVA) indicated that race was a significant predictor (P = 0.034) of positive PNB. A subgroup analysis was performed for black men undergoing PNB (n = 256). Multivariate analysis (MVA) indicates that abnormal TRUS findings; low AUASS, PV, and PSA levels; and absence of prior biopsy are all independent predictors of PNB in the black patient group. A final subgroup analysis (UVA and MVA) was performed for white men (n = 310). Only patient age and PV demonstrated significance as independent predictors of PNBs in this group. ConclusionThis prospective analysis of 569 men demonstrates that traditional indicators for PNB (abnormal DRE findings and PSA levels) are not significant predictors of prostate cancer. Independent predictors for prostate included age, low AUASS, low PV, and abnormal TRUS findings. A low AUASS (indicative of the absence of benign disease) is an important predictor of prostate cancer.

Clinical utility of proPSA and “benign” PSA when percent free PSA is less than 15%

Objectives To investigate the clinical utility of the subforms of free prostate-specific antigen (PSA), namely proPSA and “benign” PSA (BPSA), to improve cancer detection when the percent free PSA level is less than 15%. Percent free PSA, while maintaining sensitivity, has greatly improved the specificity of PSA for the early detection of prostate cancer. A low percent free PSA value indicates a greater risk of cancer, but only 30% to 50% of men with percent free PSA levels of less than 15% actually have cancer at biopsy. Methods Archived sera from 161 consecutive men who were prospectively enrolled in our Early Detection Research Network prostate cancer early detection biomarker program with a percent free PSA value of less than 15% were included in the study. Total PSA, free PSA, proPSA, and BPSA were measured for each sample. Results The mean total PSA was 6.1 ng/mL (range 1.8 to 24.0). The mean age of the study group was 62 ± 7 years. Prostate cancer was detected in 66 (41%) of 161 men. The area under the curve-receiver operating characteristic for total and percent free PSA was 0.51 and 0.54, respectively. BPSA and proPSA/BPSA both improved cancer detection compared with percent free PSA alone; the improvement was statistically significant ( P <0.001) . The area under the curve-receiver operating characteristic for proPSA/BPSA was 0.72, giving a sensitivity and specificity of 90% and 46%, respectively. Conclusions The results of our preliminary studies have suggested that the ratio of proPSA and BPSA can distinguish cancer with greater accuracy when the percent free PSA value is very low (less than 15%), and may, therefore, provide better clinical utility in this lower range of percent free PSA.

Effectiveness of percent free prostate specific antigen as a predictor of prostate cancer detection on repeat biopsy.

The aim of this study was to identify predictors that can increase the accuracy of detecting prostate cancer on subsequent biopsies. Between 1998 and 2003, a total of 235 men with prostate specific antigen (PSA) levels between 4.0 and 20 ng/mL underwent one or more systematic needle biopsies of the prostate. Of these men, 73 (31.1%) underwent one repeat biopsy and 26 (11.1%) underwent two or more repeat biopsies. We evaluated the results of prostate biopsies in relation to the morbidity of prostate cancer detected on repeat biopsies. Of the 73 men who underwent repeat biopsy, 16 (21.9%) had prostate cancer. Twenty-six men with one negative re-biopsy underwent two or more repeat biopsies, and five of these patients were found to have early stage prostate cancer. On repeat biopsy, there was a significant difference in percent free PSA between the cancer-detected group and the no-cancer-detected group (P < 0.01). A receiver operating characteristics (ROC) curve gave an optimal cut-off value for percent free PSA of 11%, demonstrating a significant difference in the cancer detection rate on repeat biopsy (P = 0.0009). Analysis of the data for re-biopsies showed that cancer-detected cases showed a raised PSA value and a simultaneously reduced percent free PSA (these differences were statistically significant). A low percent free PSA level increased the probability of a positive result in repeat biopsy. An increase in the accuracy of detecting cancer, especially on repeat biopsy, will promote the detection of more early stage prostate cancer.

Early detection of prostate cancer with low PSA cut-off values leads to significant stage migration in radical prostatectomy specimens.

The introduction of prostate-specific antigen (PSA) contributed to a shift in tumor stage at diagnosis in patients with prostate cancer. The aim of the present study was to evaluate the effects of PSA screening with low PSA cut-off values on mean total and percent-free PSA levels in patients with prostate cancers at the time of diagnosis as well as on pathologic stage and mean Gleason scores in positive biopsies and radical prostatectomy specimens. Data of 875 patients who were diagnosed with prostate cancers between 1996 and 2001 were analyzed. Patients were stratified into six groups according to the year of biopsy. Annual changes in total and percent-free PSA values, in Gleason scores of biopsies and radical prostatectomy specimens, and in pathologic stages of radical prostatectomy specimens were assessed. Mean PSA of patients diagnosed with prostate cancer decreased from 13.11 ng/ml (percent-free PSA: 11.89%) in 1996 to 7.33 ng/ml (percent-free PSA: 12.58%) in 2001 (P < 0.05). The percentage of organ-confined prostatectomy specimens increased from 64.3% in 1996 to 81.5% in 2001 (P < 0.05). However, mean Gleason scores increased from 5.23 to 6.33 over the 6 years (P < 0.05). The percentage of patients with biopsy-proven prostate cancers and PSA values below 4 ng/ml increased from 14.0% in 1996 to 39.2% in 2001. In the group with PSA values below 4 ng/ml organ-confined cancers were found in 80.0-95.2% of patients. PSAg screening with low cut-off levels has led to a significant reduction of mean baseline PSA levels in prostate cancer patients and to a significant increase in the percentage of organ-confined radical prostatectomy specimens, whereas mean Gleason scores have remained relatively constant.

Free prostate-specific antigen improves prostate cancer detection in a high-risk population of men with a normal total PSA and digitalrectal examination

Objectives Uncertainty exists regarding optimal prostate cancer screening parameters for high-risk populations. The purpose of this study is to report the use of percent free prostate-specific antigen (PSA) as an indication for biopsy in men at increased risk for developing prostate cancer who have a normal digital rectal examination (DRE) and total PSA level between 2 and 4 ng/mL. Methods African-American men and men with at least one first-degree relative with prostate cancer are eligible for enrollment into the Prostate Cancer Risk Assessment Program (PRAP) at our institution. Between October 1996 and April 2002, 310 asymptomatic high-risk men with no history of prostate cancer, benign prostatic hyperplasia (BPH), or prostatic intraepithelial neoplasia (PIN) were screened in the PRAP with DRE and total PSA. Percent free PSA was obtained in men with a total PSA between 2 and 10 ng/mL. Men with a normal DRE and total PSA between 2 and 4 ng/mL were advised to undergo transrectal ultrasound-guided (TRUS) biopsies of the prostate if the percent free PSA was less than 27%. Other indications for biopsy included an abnormal DRE or a total PSA greater than 4 ng/mL. The primary endpoint evaluated was prostate cancer detection in high-risk men with a benign prostate examination, a normal total PSA between 2 and 4 ng/mL, and percent free PSA less than 27%. Results Of the 310 men, 174 (56%) were African American and 202 (65%) had at least one first-degree relative with prostate cancer. Sixty-two of the 310 men were referred for prostate biopsy, and 40 of 62 had biopsy performed. Twenty-one of 40 men were diagnosed with prostate cancer for a cancer detection rate of 53% in all men undergoing biopsy and an overall cancer detection rate of 6.8% in this high-risk population. Thirty-seven high-risk men (median age 54 years) with a total PSA level between 2 and 4 ng/mL (median 2.7 ng/mL) and a normal DRE were found to have a percent free PSA level of less than 27% (median 16%, range 8% to 25%). Twenty-three of these 37 men (62%) proceeded with the recommended prostate biopsy. Prostatic adenocarcinoma was diagnosed in 12 of 23 men for a cancer detection rate of 52% in men undergoing biopsy and 32% in all men with a normal DRE, a total PSA between 2 and 4 ng/mL, and a percent free PSA less than 27%. All positive biopsies demonstrated clinically significant Gleason score 6 or 7 disease. In all men electing radical prostatectomy, bilateral organ-confined disease (pT2bN0M0) was confirmed. Conclusions In this unique population of men at high risk for prostate cancer, a percent free PSA of less than 27% was found to be useful for detecting early-stage but clinically significant cancers in men with a total PSA value between 2 and 4 ng/mL and normal DRE findings.

Predictors of cancer in repeat extended multisite prostate biopsy in men with previous negative extended multisite biopsy

Objectives To evaluate the factors influencing the cancer detection rate in men whose initial and repeat biopsies were both performed using an extended multisite biopsy scheme.Sextant biopsy of the prostate is associated with a significant false-negative rate, as evident from the high cancer detection rate after repeat prostate biopsy. Extended multisite biopsy schemes have therefore been recommended to maximize cancer detection. Methods Between June 1997 and August 2001, 939 men underwent prostate biopsy for early detection of prostate cancer using the extended multisite scheme (10 or 11 cores incorporating the anterior horn of the peripheral zone with or without midline peripheral zone and/or the transition zone). Of these 939 men, 89 (9.5%) underwent a repeat extended multisite prostate biopsy. The median prostate-specific antigen level was 6.9 ng/mL (range 0.7–36.1). Twenty-four men (27%) had an abnormal digital rectal examination at presentation. Most men (86%) in the group undergoing repeat biopsy had two or more risk factors for a positive biopsy. The median interval between biopsies was 4 months. Results Of the 89 men, 15 (17%) had prostate cancer in the repeat biopsy specimen. Seven cancers (47%) were found only in the alternate biopsy sites, 5 (33%) cancers were found only in the sextant sites, and 3 in both sextant and alternate sites. Cancer was present in only one biopsy core in 11 (73%) of the 15 men, and the median Gleason score was 6 (range 6–8). On multivariate analysis, the presence of atypical glands suspicious for carcinoma (AGSC) was the only independent predictor of cancer in repeat biopsy ( P <0.004). Of the 79 men without AGSC in the initial biopsy, 8 (10%) had a positive repeat biopsy. The total and percent free prostate-specific antigen level, digital rectal examination, ultrasound findings, and presence of high-grade prostatic intraepithelial neoplasia were not predictive of cancer detection. Conclusions The probability of a positive result for a repeat prostate biopsy is lower after an initial extended multisite biopsy compared with an initial sextant biopsy. The presence of AGSC was the only significant predictor of cancer in the repeat biopsy. Because nearly 50% of cancers detected in the repeat biopsy were in alternate sites only, using a sextant biopsy scheme for repeat biopsy would have missed these cancers.

Correlation between inflammatory cells (T and B lymphocytes, macrophages) in prostate biopsies and elevated PSA levels in a PSA screening population

Objectives. To investigate the relationship between inflammatory cells in prostate biopsies and total serum prostate-specific antigen (PSA) levels in a screening population. Methods. In the study, transrectal ultrasound-guided prostate biopsy specimens from 49 patients were assessed. All patients undergoing biopsy had elevated serum PSA levels (as defined by the biopsy criteria of the Tyrol PSA Screening Project) and/or abnormal findings on digital rectal examination. The prostate biopsy specimens were histologically negative for carcinoma. Immunohistologic characterization of the inflammatory cells was performed using CD3, CD4, and CD8 antibodies for the detection of T lymphocytes, CD20 antibodies for B lymphocytes, and CD68 antibodies for macrophages. The percentage of inflammatory cells and their distribution in stromal and glandular tissue was estimated using morphometric methods. Results. Inflammatory cells in the stroma contained significantly larger numbers of T lymphocytes than B lymphocytes and macrophages. T lymphocytes were also predominant in the glandular region. A significant positive correlation was found between the relative volume (vol%) of macrophages and total PSA levels ( P <0.05) and a significant negative correlation between the percent free PSA levels and the relative volumes of T and B lymphocytes. Conclusions. The results indicate a significant positive correlation between total PSA levels and macrophages and a significant negative correlation between percent free PSA levels and T and B lymphocytes. No statistically significant correlation was found between total serum PSA levels and the presence of inflammatory cells in the stromal and glandular compartment. Additional studies are needed to compare the amount and types of inflammatory cells with the stage and grade of prostate cancer in positive biopsies and radical prostatectomy specimens.

Effect of antibiotic treatment on serum PSA and percent free PSA levels in patients with biochemical criteria for prostate biopsy and previous lower urinary tract infections.

Controversy exists as to the influence of inflammatory foci on total and free prostate-specific antigen (PSA) concentrations. The objective was to analyze the biological variations of PSA and percent free PSA (%f-PSA) in patients with biochemical criteria for prostate biopsy (PSA higher than 4 ng/mL and normal rectal examination) and compare them with the variation induced by antibiotic treatment in a cohort of patients with a history of lower urinary tract infections and no clinical evidence of prostatitis. Ninety patients with a history of lower urinary tract infections, non-suspicious digital rectal examination and PSA between 4 and 20 ng/mL were analyzed. PSA concentration and %f-PSA were determined. Forty-five patients were treated with three weeks of ofloxacin, following which marker determination was repeated. All patients underwent ultrasound-controlled transrectal six-core prostate biopsy. Sixty-seven patients presented benign prostatic hyperplasia (BPH) (30 with prostatitic foci) and 23 cancer. Significant variations in PSA (6.97 ng/mL vs. 5.82 ng/mL, p=0.001) and %f-PSA (14.84% vs. 17.53%, p=0.01) were found only in the treated patients. These differences were significant for patients with BPH-associated prostatitic foci and not for patients with BPH or cancer. The tendency was for PSA to decrease (15 treated patients with PSA <4 ng/mL vs. six non-treated patients) and for %f-PSA to increase. The median variation of %f-PSA was greater than that of PSA. When the cutoff for %f-PSA was set at 25%, 18.9% of unnecessary biopsies after the first determination and 20% after the second could be avoided. By associating the reduction in PSA, up to 46% could be avoided in treated patients. Biochemical criteria for prostate biopsy may be modified in patients with a history of lower urinary tract infections due to variations greater than those explained by intraindividual biological variations, and may be influenced by the antibiotic treatment. These results suggest that subclinical inflammatory foci may influence PSA and %f-PSA.

PREDICTIVE VALUE OF TOTAL AND PERCENT FREE PROSTATE SPECIFIC ANTIGEN IN HIGH GRADE PROSTATIC INTRAEPITHELIAL NEOPLASIA LESIONS: RESULTS OF THE TYROL PROSTATE SPECIFIC ANTIGEN SCREENING PROJECT

We evaluate the predictive values of total and percent free prostate specific antigen (PSA) in regard to high grade intraepithelial lesions in volunteers who participated in the Tyrol PSA Screening Project. Between June 1995 and December 1998, 1,474 patients undergoing transrectal biopsy of the prostate were evaluated. The primary detection rates of prostate cancer and high grade intraepithelial lesions were evaluated. In addition, the rate of prostate cancer detected on biopsy in patients diagnosed with high grade prostatic intraepithelial neoplasia on the previous biopsy was assessed. Mean total PSA values and mean percent free PSA levels were determined for each study group and compared using the Mann-Whitney U test. A total of 1,077 (73.1%) volunteers had benign prostatic hyperplasia or prostatitis, and 327 (22.2%) had prostate cancer. The primary detection rate for high grade intraepithelial lesions was 4.7% (70 patients) and on repeat biopsy was 38.6% (27). Mean total PSA for the benign prostatic hyperplasia, prostate cancer, high grade and intraepithelial cancer groups were 6.0, 8.7, 5.9 and 5.2 ng./ml., respectively. Mean percent free PSA values for the various groups were 21.9, 12.1, 15.0 and 12.0, respectively. In regard to total PSA there was a statistically significant difference between the prostate cancer and high grade prostatic intraepithelial neoplasia groups (p = 0.016), as well as the prostate cancer and intraepithelial cancer groups (p = 0.028). However, the high grade and intraepithelial cancer groups did not differ significantly. In regard to percent free PSA there were statistically significant differences between the prostate cancer and high grade prostatic intraepithelial neoplasia groups (p = 0.0001), and the high grade and intraepithelial cancer groups (p = 0.013). In regard to percent free PSA our data indicate a significant difference between high grade intraepithelial lesion and intraepithelial cancer. Due to a substantial overlap in percent free prostate specific antigen between the 2 groups, a clinically useful cutoff point could not be established. Therefore, we recommend repeat biopsy in all patients with high grade intraepithelial lesions regardless of the percent free PSA.

Comparison of the percent free prostate-specific antigen levels in the serum of healthy men and in men with recurrent prostate cancer after radical prostatectomy

The percentage of free PSA in serum is currently used to better discriminate between patients with prostate cancer and patients with benign prostatic hyperplasia, in prostate cancer screening programs. We measured using non-competitive immunological techniques, the total PSA and free PSA in post-surgical serum of prostate cancer patients who underwent radical prostatectomy and then relapsed. We compared these data with those of a group of 40 age-matched men with no evidence of prostatic disease. Although in general, patients with prostate cancer had lower percentage of free PSA in serum in comparison to the controls, a subset of these patients (approximately 20%) had percent free PSA significantly higher than the levels considered as exclusive of prostate cancer in screening programs. We also found that percent free PSA does not correlate significantly with most of the standard clinical or pathological indicators of prostate cancer aggressiveness. Only a weak negative association with Gleason Score was observed. The percent free PSA in serum of relapsing prostate cancer patients varies within a relatively wide range and does not correlate significantly with indicators of cancer aggressiveness. The use of percent free PSA for excluding prostate cancer in screening programs must be approached with caution until the mechanism of low percent free PSA in the majority but not all prostate cancer patients is elucidated.

PREDICTION OF POST-RADICAL PROSTATECTOMY PATHOLOGICAL OUTCOME FOR STAGE T1c PROSTATE CANCER WITH PERCENT FREE PROSTATE SPECIFIC ANTIGEN: A PROSPECTIVE MULTICENTER CLINICAL TRIAL

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. 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. 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. 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.

Correlation between preoperative predictors and pathologic features in radical prostatectomy specimens in PSA-based screening.

Measurement of percent free prostate-specific antigen (PSA), PSA density, and PSA-transition zone density (PSA-TZ density) in addition to total PSA is known to improve the specificity of PSA-based prostate cancer screening. We evaluated the ability of total PSA, percent free PSA, PSA density, and PSA-TZ density to predict pathologic features in radical prostatectomy specimens. The levels of total PSA, percent free PSA, PSA density, and PSA-TZ density assessed prior to the diagnosis of prostate cancer were correlated with the pathologic findings in 102 prostate glands with cancer obtained at radical prostatectomy. The entire organs were examined histologically; Pearson correlation coefficients were used for statistical analysis. High levels of total PSA, PSA density, and PSA-TZ density correlated significantly with capsular penetration, high Gleason scores, and large cancer volumes in the prostatectomy specimens. Free PSA was found to correlate well with high Gleason scores, high percentages of cancer, and large cancer volumes, but not with capsular penetration. The four parameters were evaluated by means of logistic regression, which showed that only percent free PSA and total PSA were significant predictors of Gleason scores > or =7 and cancer volumes > or =0.5 cc. With regard to clinically insignificant cancers, only percent free PSA and the Gleason score obtained at biopsy were significant predictors. In men whose prostate cancers are detected by PSA-based screening, high total PSA levels in combination with low percent free PSA levels are suggestive of a potentially more aggressive type of prostate cancer. This may help both patient and clinician in selecting the most appropriate therapeutic approach.

THE EFFECT OF PROSTATE VOLUME, AGE, TOTAL PROSTATE SPECIFIC ANTIGEN LEVEL AND ACUTE INFLAMMATION ON THE PERCENTAGE OF FREE SERUM PROSTATE SPECIFIC ANTIGEN LEVELS IN MEN WITHOUT CLINICALLY DETECTABLE PROSTATE CANCER

Purpose We determine the influence of age, prostate volume, total serum prostate specific antigen (PSA) level and histological evidence of acute inflammation in biopsy specimens on the percent free serum PSA level in men without clinically detectable prostate cancer. Materials and Methods We studied 70 men with total PSA levels of 2.6 to 9.9 ng./ml. who had undergone at least 3 sets of prostate biopsies that were negative for cancer as part of our PSA based prostate cancer screening program. Total and free PSA levels were measured using Hybritech immunoassays. Prostate volume and the presence of acute inflammation were determined from the most recent transrectal ultrasonography and prostate needle biopsy. Results Percent free PSA levels correlated significantly with age (r = 0.48, p = 0.0001) and prostate volume (r = 0.44, p = 0.0002) but not with total PSA (r = 0.04, p = 0.7). The mean percent free PSA did not differ for those with or without acute inflammation. Multivariate regression models demonstrated that age and prostate volume were significant predictors of percent free PSA. Conclusions Among men without detectable prostate cancer and a total PSA level between 2.6 and 9.9 ng./ml. percent free serum PSA was higher in older men and in men with a larger prostate gland but was not influenced by total PSA level or the presence of acute inflammation in the prostatic biopsy specimen.

Comparison of percent free prostate-specific antigen levels in men with benign prostatic hyperplasia treated with finasteride, terazosin, or watchful waiting

Objectives Finasteride is known to lower total serum prostate-specific antigen (PSA) levels by approximately 50%. Terazosin is thought to have little or no effect on serum PSA concentration. The objective of our study was to determine the effect of finasteride and terazosin on serum total and serum free PSA levels and the ratio of free to total PSA. Methods We identified 69 men with symptomatic benign prostatic hyperplasia (BPH) who had been receiving 5 mg/day (n = 33) of finasteride or 2 to 5 mg/day (n = 14) of terazosin or no therapy (“watchful waiting”) (n = 22). The three groups were compared with respect to pretreatment total serum PSA levels and post-treatment total, free, and percent free serum PSA levels. Results Median (± semi-interquartile range [SIR]) pretreatment total serum PSA levels (ng/mL) were not significantly different in men taking finasteride (2.8 ± 1.9), terazosin (2.2 ± 2.5), or undergoing watchful waiting (5.5 ± 1.4) ( p = 0.12). The median (± SIR) post-treatment total serum PSA levels (ng/mL) were significantly lower in the finasteride group (1.1 ± 1) when compared with the terazosin (2.5 ± 1.5) or watchful waiting (4.3 ± 2.8) groups ( p = 0.016). Only the finasteride group had significantly lower post-treatment total serum PSA levels compared with pretreatment levels. The median (± SIR) post-treatment free PSA levels were significantly lower in the finasteride group (0.26 ± 0.16) compared with the terazosin (0.54 ± 0.5) and watchful waiting (0.85 ± 0.5) groups ( p = 0.0015). However, the median (± SIR) percent free PSA was not significantly different in the finasteride (23 ± 6), terazosin (22 ± 4), and watchful waiting (25 ± 5) groups ( p = 0.66). Conclusions Finasteride appears to lower total and free PSA levels equally in men with BPH and does not appear to change the ratio of free to total serum PSA. Terazosin does not appear to alter total or free serum PSA levels in men with BPH. The percent free PSA could potentially be used to screen for prostate cancer in men taking finasteride. Prospective studies are needed to further evaluate this issue.