Effect of high-grade prostatic intraepithelial neoplasia on total and percent free serum prostatic-specific antigen

OBJECTIVE: To analyze the influence of high-grade prostatic intraepithelial neoplasia (HGPIN) on total serum prostatic-specific antigen (PSA) and percent free PSA. METHODS: Total and free serum PSA were determined in 81 consecutive patients with clinical T1c prostate cancer who underwent radical prostatectomy. HGPIN was detected in 62 specimens (76.5%). RESULTS: Median total PSA was 9.2 ng/ml when there was not HGPIN and 8.1 ng/ml when it existed, p>0.05. Median percent free PSA was 11.7 and 9.1%, respectively, p<0.03. However, a multiple linear regression analysis demonstrated there was no effect of HGPIN on total PSA nor on percent free PSA. Percent free serum PSA was significantly influenced by total PSA and the pathological tumor stage. CONCLUSION: HGPIN does not seem to contribute significantly on serum total PSA and percent free PSA.     

Influence of high-grade prostatic intra-epithelial neoplasia on total and percentage free serum prostatic specific antigen.

OBJECTIVE: To analyse the influence of high-grade prostatic intra-epithelial neoplasia (HGPIN) on total and percentage free serum prostatic specific antigen (PSA). PATIENTS AND METHODS: The total and free serum PSA levels were measured (using a double-monoclonal antibody immunoassay, Tandem and Tandem free PSA, Hybritech Inc, Liège, Belgium) in 570 consecutive patients undergoing sextant ultrasound-guided prostatic biopsy because of an abnormal digital rectal examination or a serum PSA concentration of > 4.0 ng/mL. The main diagnosis was benign disease in 321 (56%) and prostate cancer in 249 (44%). HGPIN was detected in 85 (15%) of the patients; in 17 (20%) it was associated with benign tissue and in 68 (80%) with prostate cancer. RESULTS: Patients with benign disease had a median total serum PSA level of 7.2 with no HGPIN and 7.7 ng/mL when HGPIN was present (P>0.05); the corresponding values in patients with prostate cancer were 16.0 and 15.9 ng/mL (P>0.05). The median percentage free serum PSA was 15.8 in patients with HGPIN-free benign disease and 14.1 when HGPIN was present (P>0.05); the corresponding values in patients with prostate cancer were 9.7 and 11.0 (P>0.05). In a multivariate analysis, prostate cancer was the major contributor to total and percentage free serum PSA levels. CONCLUSION: The presence of HGPIN does not contribute significantly to total and percentage free serum PSA levels.     

Intraindividual variations of total and percent free serum prostatic-specific antigen levels in patients with normal digital rectal examination.

PURPOSE: To analyze intraindividual variations of total and percent free serum prostate-specific antigen (PSA) in patients with normal digital rectal examination. MATERIAL AND METHODS: Total and free serum PSA were determined in two blood samples corresponding to 107 nonconsecutive patients. The period between both determinations ranged from 23 to 60 days. Prostatic biopsy was done after both determinations in all except 17 patients because the two serum PSA concentrations were <4 ng/ml. Total and free PSA were determined using double monoclonal antibody immunoassay Tandem and Tandem free (Hybritech Inc.). The diagnosis was benign prostatic hyperplasia (BPH) in 63 patients and prostate cancer (PCA) in 44. RESULTS: The variations of PSA ranged between -6.8 and +3.2 ng/ml in BPH patients and between -2.8 and +9.0 in patients with PCA. The median coefficients of variation were 15.4 and 15.7% respectively. The variations in the percent free PSA were between -30.7 and +40.9 in the BPH group and between -17.9 and +15.8 in the PCA group. The median coefficients of variation were 32.2 and 32.3% respectively. If prostatic biopsy had been indicated when percent free PSA had been 相似文献   

The percentage of free prostatic-specific antigen is also useful in men with normal digital rectal examination and serum prostatic-specific antigen between 10.1 and 20 ng/ml

OBJECTIVE: The percentage of free prostatic-specific antigen (PSA) has been introduced as a tool to avoid unnecessary biopsies in men with normal digital rectal examination (DRE) and serum PSA between 4.1 and 10 ng/ml. In this series we also analyze its utility in men with normal DRE and serum PSA between 10.1 and 20 ng/ml. MATERIALS AND METHODS: A series of 1149 consecutive men with normal DRE and serum PSA between 4.1 and 20 ng/ml submitted for the first ultrasound guided sextant biopsy is analyzed. In 921 (80.2%) the serum PSA was from 4.1 to 10 ng/ml and in 228 (19.8%) from 10.1 to 20 ng/ml. Total and free serum PSA determinations were done by the inmunoradiometric assays Tandem and Tandem free PSA (Hybritech Inc.). RESULTS: The overall detection rate of prostate cancer was 27.9%. In the group of men which serum PSA ranged from 4.1 to 10 ng/ml the rate of detection was 25.4% and 37.7% when it was between 10.1 and 20 ng/ml. Using 25% or less of percent free PSA as a criterion for performing prostatic biopsy it would have detected 95.3% and 95.4% of the prostate cancers, respectively. The rate of unnecessary avoided biopsies would be 17.5% when serum PSA ranged from 4.1 to 10 ng/ml and 17.6% between 10.1 and 20 ng/ml. CONCLUSIONS: This prospective study demonstrates that the percentage of free PSA seems to have similar utility when serum PSA levels are between 4.1 and 10 ng/ml and between 10.1 and 20 ng/ml, at the time of the first prostatic biopsy indication.     

Efecto del tratamiento antibiótico sobre el psa y porcentaje de psa libre en pacientes con criterios bioquímicos de biopsia prostática

IntroductionPSA serum level measurement in the most important tool in the early diagnosis of prostate cancer patients. However, it is recognised it low specificity is due mainly to prostatic benign diseases. Although it is known that immflamation can contribute on this lack of specificity, there is disagreement in the effect of no symptomatic prostatic immflamatory focus on total PSA and percent free PSA serum levelsAimTo analyse the biological variability in total PSA and percent free PSA serum levels in patients with biochemical criteria of prostatic biopsy and to compare them with the antibiotic induced variability in a previous urinary infections cohort patientsPatients and methodsWe analysed 60 patients with previous urinary infections, normal digital rectal examination and PSA between 4 and 20 ng/ml. We measured total PSA and percent free PSA serum levels. Thirty were treated with 3 weeks of ofloxacin and following a new marker determination. Sextant ultrasound guided prostatic biopsy was performed in all casesResults45 patients demonstrated BPH (29 with prostatitis) and 15 prostate cancer (T1c). Significant variations were found on total PSA serum levels (6.97 ng/ml vs 5.82 ng/ml, p = 0,001) and percent free PSA (14.73% vs 17.77%, p = 0,01) only in treated patients. These differences were significant in BPH and BPH with prostatitis patients but not in prostate cancer patients. Treated patients trend was to decrease PSA (13 treated patients shown PSA < 4 ng/ml vs 2 control patients) and to increase percent free PSA. The median variation of percent free PSA was higher than total PSA and was not influenced by PSA level or prostatic volume. Taking 25 as cut-off of percent free PSA, 18.3% of prostatic biopsies could be avoided in the first determination and 20% in the second. Adding the total PSA reduction, 56% of prostates biopsies in the treated patients could be avoidedConclusionsBiochemical criteria of prostatic biopsy could be modified in patients with previous urinary infections due to higher variations on serum markers than those explained by biological variations. These variations could be induced by the antibiotic treatment. These results suggested that the immflamatory focus could influence on total PSA and percent free PSA serum levels     

Determination of the percentage of free prostate-specific antigen helps to avoid unnecessary biopsies in men with normal rectal examinations and total prostate-specific antigen of 4-10 ng/ml

OBJECTIVE: To assess the usefulness of measuring the percentage of free prostate-specific antigen (PSA) in serum to reduce the number of prostate biopsies in men with serum PSA levels between 4 and 10 ng/ml and benign prostate examinations. MATERIALS AND METHODS: The percentage of free PSA (Immulite((R))) in serum was analyzed prospectively in 180 men with benign digital rectal examinations and total PSA serum levels of between 4 and 10 ng/ml. All patients underwent ultrasound-guided sextant prostatic biopsies. Sensitivity, specificity and positive and negative predictive values were calculated as well as the percent of patients in which biopsies could have been avoided for various cutoff values of the percentage of free PSA as an indicator for biopsy. Influence of age in the determination of cut points was evaluated. RESULTS: Cancer was detected in 22.2% (40/180) of the patients. Mean percentage of free PSA was 13.4% in patients with cancer and 18.9% in patients with benign prostatic hyperplasia (p = 0.001). Using a percentage of free PSA cutoff of 22% or less as a criterion for performing prostatic biopsy would have detected 95% of cancers, avoided 25% of benign biopsies and yielded a positive predictive value of 29% in patients who underwent biopsy. Mean percent of free PSA values increased as mean subject age increased, influencing the calculation of cut points, sensitivity and specificity. Leaving the cut point constant across all age groups will oblige older patients to undergo an increased number of unnecessary biopsies, although allowing for higher sensitivity in younger men. CONCLUSIONS: Measurement of the percentage of free serum PSA improves specificity of prostate cancer detection in patients with elevated total serum PSA levels and benign prostate examinations. Subject age seemed to influence the determination of optimal cut points.     

Diagnostic accuracy of percent free prostate-specific antigen in prostatic pathology and its usefulness in monitoring prostatic cancer patients.

INTRODUCTION: The aim of our study was to evaluate the clinical usefulness of percent free prostate-specific antigen (PSA) [ratio of free PSA (fPSA) to total PSA (tPSA); f/tPSA] in prostatic pathology and its usefulness in monitoring prostatic cancer patients. PATIENTS AND METHODS: Our prospective study was carried out on 470 consecutive male patients referred to our outpatient urological clinic for observation. We looked for relationships between tPSA, fPSA and percent free PSA and the patient's age, prostatic volume and histologic diagnosis as assessed by prostatic biopsies or surgical specimens (benign prostatic hypertrophy, carcinoma, hypertrophy with inflammation). In all cases, we calculated the specificity, sensitivity and diagnostic accuracy of percent free PSA in the diagnosis of prostatic diseases, using cutoff values ranging from 14 to 20%. In prostatic cancer patients, we considered the relationships between the various PSA molecular forms and staging, grading and follow-up values. We also evaluated the effects of hormonosuppressive therapy on the serum markers and noted for which tPSA value percent free PSA possessed the greatest diagnostic accuracy. RESULTS: While tPSA and fPSA values appeared to be correlated with patient age and prostatic volume, percent free PSA did not show a relationship with these parameters. The specificity, sensitivity and overall diagnostic accuracy were better assuming a 16% cutoff value for percent free PSA than with other cutoff values. Prostatic inflammation associated with benign hypertrophy can cause false positives in both tPSA and f/tPSA measurements, since 60% of these patients have an f/tPSA ratio below 16%. In diagnosing carcinoma, the diagnostic accuracy of percent free PSA is 100% when tPSA is between 2.5 and 4.0 ng/ml. Percent free PSA is not linked with staging in prostatic cancer, but it does appear to be related to the Gleason score. In patients receiving hormonosuppressive treatment, f/tPSA decreased significantly, and more so in patients with a higher Gleason score. In patients with disease in rapid progression, percent free PSA was lower than in patients in a stable condition. CONCLUSIONS: Based on our experience, 16% as the f/tPSA cutoff value for discriminating between benign and malignant pathologies is the best possible choice, as it provides the highest overall values of sensitivity, specificity and diagnostic accuracy (80, 61.5 and 84.5%, respectively) in the diagnosis of prostatic cancer. We believe that f/tPSA is not a definitive test for diagnosing prostatic cancer. Our observations on the behavior of percent free PSA in relation to prostatic carcinoma grading and staging and in the follow-up of carcinoma patients are interesting; however, further studies are needed to define the appropriate role of f/tPSA in patients with an established diagnosis of prostatic carcinoma and in the follow-up of patients with prostatic cancer.     

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

PURPOSE: 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. MATERIALS AND METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.     

Percent free prostate specific antigen and cancer detection in black and white men with total prostate specific antigen 2.5 to 9.9 ng./ml

PURPOSE: The ratio of free-to-total prostate specific antigen (PSA), or percent free PSA, is a useful adjunct to total PSA for estimating the risk of prostate cancer when total PSA is 2.5 to 9.9 ng./ml. Relationships between cancer detection and total PSA are influenced by race but to our knowledge relationships between cancer detection and percent free PSA have not been studied. MATERIALS AND METHODS: A total of 222 black and 298 white consecutive and evaluable men with total PSA 2.5 to 9.9 ng./ml. underwent prostate biopsy for suspected cancer at a Veterans Affairs Medical Center. Clinical measurements included digital rectal examination, total and free serum PSA, prostate volume, PSA density and Gleason score of malignant biopsy specimens. RESULTS: Median percent free PSA was 14.1 (range 3.6 to 49.2) in 201 men with prostate cancer and 21.9 (range 5.7 to 83.3) in 319 without detectable cancer (p <0.0001). Significant racial differences in demographic characteristics and clinical measurements were limited to total PSA, which was higher in black men (p = 0.03). Cancer was detected in 156 black (47%) and 206 white (33%) men (p = 0.001). Areas under receiver operating characteristics curves for percent free PSA and total PSA were 0.66 and 0.58, respectively, for black men (p = 0.15), and 0.76 and 0.58, respectively, for white men (p <0.00001). Percent free PSA was 35.2 in black men and 29.2 in white men, and specificity was 9.1% and 28.7%, respectively, when sensitivity for percent free PSA was set at 95%. Of 156 black and 206 white men with percent free PSA less than 25, 83 (53%) and 85 (41%), respectively, had detectable cancer (p = 0.03). Of 66 black and 92 white men with percent free PSA 25 or greater 21 (32%) and 12 (13%), respectively, had detectable cancer (p = 0.005). CONCLUSIONS: Our study demonstrates racial differences in relationships between percent free PSA and cancer detection in men with suspected prostatic carcinoma and total PSA 2.5 to 9.9 ng./ml. Clinical application of the commonly used percent free PSA cutoff of less than 25 to determine the advisability of prostate biopsy may lead to under diagnosis of early stage prostate cancer in black men, who are at greater risk of morbidity and mortality from disease than white men.     

Relation between acute urinary retention, chronic prostatic inflammation and accompanying elevated prostate-specific antigen

OBJECTIVE: To determine if there is a relationship between acute urinary retention (AUR), the prostate-specific antigen (PSA) level and chronic inflammation of the prostate. We therefore studied patients with benign prostatic obstruction (BPO) with (n = 64) or without (n = 168) acute urinary retention (AUR) who underwent transurethral resection of the prostate (TURP) in a retrospective case control study. MATERIAL AND METHODS: Between 2001 and 2004, a total of 232 patients underwent TURP due to BPO with or without AUR. The mean values of age, prostate volume, weight of resected prostate and PSA level and the histopathologic results of patients with and without AUR were compared. Chi(2) analysis was used to examine the relationship between prostatic inflammation and AUR. The contribution of each variable to AUR was assessed by means of multiple linear regression. RESULTS: A total of 64 patients (28%) were operated on for AUR due to BPO. There were no statistical differences between patients with or without AUR with respect to the mean values of PSA, percent free PSA, prostate size or weight of the resected prostate tissue. Elevated PSA values (>or=4.0 ng/ml) were detected in 64% and 38% of the patients in the AUR and non-AUR groups, respectively (p = 0.01). Histopathological re-evaluation demonstrated that chronic prostatic inflammation was present in 56% and 37% of the specimens in the AUR and non-AUR groups, respectively (p = 0.014). In the AUR group, the mean PSA level was significantly higher in patients with than without prostatic inflammation (7.75+/-5.26 vs 5.07+/-3.21 ng/ml; p = 0.022). The odds ratio of AUR for patients with chronic prostatic inflammation and elevated PSA was determined as 4.14 (95% CI 1.65-10.41). Multiple linear regression revealed that prostatic inflammation made a significant contribution to AUR. CONCLUSIONS: Chronic prostatic inflammation may be histopathological evidence of both elevated PSA level and AUR; hence it may play a role in the pathophysiology of AUR.     

Complexed prostate specific antigen provides significant enhancement of specificity compared with total prostate specific antigen for detecting prostate cancer

PURPOSE: Determining serum total prostate specific antigen (PSA) has proved to be a valuable diagnostic aid for detecting prostatic carcinoma, although the lack of specificity has limited its usefulness. Studies indicate that the use of percent free PSA would improve specificity while maintaining sensitivity. Since complexed PSA represents the major proportion of measurable PSA in serum, we determined whether it represents a single test alternative to the use of percent free PSA for the early detection of prostate cancer. MATERIALS AND METHODS: Archival serum was obtained from 385 men with no evidence of malignancy on biopsy and 272 with biopsy confirmed prostate cancer. We determined the concentration and proportion of total, complexed and free PSA. RESULTS: Receiver operating characteristics analysis using total PSA results from all samples (range 0.32 to 117 ng./ml.) indicated that the areas under the curve for complexed PSA alone as well as the free-to-total and complexed-to-total PSA ratios were similar and significantly greater than those for total PSA alone. Within the range of 85% to 95% sensitivity receiver operating characteristics analysis revealed that the specificity of complexed PSA was higher than that of total PSA and equivalent to that of the free-to-total PSA ratio. We noted a similar improvement in specificity in the 4 to 10 ng./ml. total PSA range. Using published cutoff values for complexed, total and percent free PSA when total PSA was in the 4 to 10 ng./ml. range the sensitivity and specificity of complexed and percent free PSA were similar. Within the 4 to 10 ng./ml. total PSA range the population of patients with no evidence of malignancy and complexed PSA below the upper limit was different with respect to total PSA from that with no evidence of malignancy and free PSA greater than 25%. CONCLUSIONS: The measurement of complexed PSA represents an alternative to the use of percent free PSA, although the patient populations identified by the 2 tests are different.     

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.     

Effects of antibacterial therapy on PSA change in the presence and absence of prostatic inflammation in patients with PSA levels between 4 and 10 ng/ml

We investigated the effect of prostatic inflammation on prostate-specific antigen (PSA) and per cent-free PSA levels changing after antibacterial therapy. We evaluated 48 patients whose PSA levels were between 4 and 10 ng/ml, without any suspicious findings on digital rectal examination, with no infection findings in urine analysis. Prostatic inflammation was assessed with prostatic massage. All the patients were given antibiotic therapy for 3 weeks. Patients were re-evaluated 3 weeks after antibacterial therapy with PSA (free/total) and urinalysis. Ten core biopsies were taken with transrectal ultrasound. No differences were found in terms of age, pre- and post-treatment PSA, and PSA varying between patients with and without inflammation in the prostatic massage. In 18 patients, PSA decreased below 4 ng/ml. Prostate cancer was found in 10.8% of the patients with PSA between 4 and 10 ng/ml and none of the patients with PSA values below 4 ng/ml. We suggest an antibiotic therapy for 3 weeks without regarding inflammation findings when PSA is in the gray zone, for biopsy decision.     

超声引导下经会阴穿刺活检在前列腺癌诊断中的价值

目的：探讨超声引导下经会阴道前列腺穿刺活检诊断前列腺癌的价值。方法：对376例临床怀疑前列腺癌患者行直肠腔内超声引导下经会阴前列腺穿刺活检。分3组。A组：184例,为指检前列腺触及结节或前列腺增大、质硬怀疑前列腺癌者;B组：84例,为因前列腺增生行直肠腔内超声检查发现有异常回声区域者;C组：108例,为指检未及明显硬节而血中PSA＞10ng/ml者。结果：3组穿刺活检阳性率分别为44．5％（82／184）,29．8％（25／84）,57．4％（62／108）。结论：直肠腔内超声引导下经会阴穿刺活检取材准确,能清楚显示穿刺针的径路和深度,避免损伤邻近脏器,可重复操作,明显提高穿刺活检的阳性率。     

Percent of free serum prostate-specific antigen and histological findings in patients undergoing open prostatectomy for benign prostatic hyperplasia

PURPOSE: To determine which pathologic features of the surgical specimen in men undergoing open prostatectomy for benign prostatic hyperplasia (BPH) correlate with preoperative and postoperative total, free prostate-specific antigen (PSA) levels and the free-to-total PSA ratio. METHODS: Forty-four patients, undergoing open prostatectomy for BPH without evidence of prostate cancer in systematic biopsies and clinical prostatitis, were included in this prospective study. Each prostatectomy specimen was weighed and each slide was evaluated for inflammation (acute prostatitis, chronic-active prostatitis and chronic-inactive prostatitis), prostatic intraepithelial neoplasia, transitional/squamous metaplasia, cystic ductal dilation, leiomyoma-resembling stromal cell proliferation, leakage of prostatic secretion, infarction and prostatic calculi. RESULTS: The mean preoperative (and postoperative) total PSA and free PSA levels were 6.1 +/- 4.3 (1.14 +/- 0.87) and 1.7 +/- 1.6 (0.24 +/- 0.19) ng/ml, respectively. The mean prostatic and transition zone volume was 83.9 +/- 28.4 and 55.4 +/- 27.6 cm(3), respectively. Both total PSA and free PSA levels were correlated with total gland volume (p = 0.0001; p = 0.002) and the volume of the surgical specimen (p = 0.003; p < 0.05) and, upon stepwise logistic analysis, patients with a total gland volume of <50 cm(3) had an odds ratio of 11 (CI 1.6-71.3) for having a free-to-total ratio of <18%. No minimal change pathology or prostatic inflammation were associated with preoperative total or free PSA levels. The free-to-total PSA ratio was higher in the group of patients with histologically acute and moderate to severe chronic-active prostatitis (mean ratio 27 +/- 12%) than in patients with chronic-inactive prostatitis and minimal chronic-active prostatitis (mean ratio 0.19 +/- 13%; p = 0.05), showing an odds ratio of 5 (CI 1.1-22.1) for having a free-to-total PSA ratio of <18%. CONCLUSIONS: Prostate volume and, in particular, transition zone volume seem to influence both free and total PSA levels in men with BPH. The free-to-total PSA ratio seems to be influenced by the presence of histological prostatitis in the surgical specimen. In particular, patients with a prostate volume of <50 cm(3) and an inactive form of prostatitis seem to have a relatively higher risk of having a free-to-total PSA ratio of <18%.     

Inflammation in prostate biopsies of men without prostatic malignancy or clinical prostatitis: correlation with total serum PSA and PSA density

OBJECTIVE: Inflammation is a frequent histological finding in prostate biopsies, performed on men without prostatic malignancy or clinical prostatitis. We investigated the relationship between morphological parameters of inflammation in prostatic tissue and total serum prostate-specific antigen (PSA) and prostate-specific antigen density (PSAD) levels to determine if subclinical inflammation can cause elevation of PSA and PSAD. METHODS: We reviewed 268 prostate biopsies, performed on 238 men with elevated PSA and/or abnormal digital rectal examination of the prostate. All premalignant and malignant biopsies and cases of clinical prostatitis were excluded. The inflammation in the remaining 145 prostate biopsies was scored for extent of inflammation and aggressiveness of inflammation, using the four-point scale designed by Irani and co-workers. In this prostatic inflammation scoring system, extent of inflammation is graded from 0 up to 3 according to the degree of invasion of inflammatory cells in prostatic tissue. Aggressiveness of inflammation is graded from 0 up to 3 according to the degree of contact or disruption of prostatic glandular epithelium by inflammatory cells. RESULTS: Each of the studied biopsies showed inflammatory cells. Median PSA levels in grades 1, 2 and 3 of extent of inflammation were, respectively, 5.7, 6.8 and 13. 0. Median PSAD levels in these groups were 0.13, 0.16 and 0.33. There was no significant difference between these grades for PSA nor for PSAD. Median PSA levels in grades 0, 1 and 2 of aggressiveness of inflammation were, respectively, 3.9, 5.9 and 8.9. Median PSAD levels in these groups were 0.12, 0.18 and 0.17. For both parameters, there was a significant difference between grades (respectively, p = 0.0028 and p = 0.0330). CONCLUSION: Inflammation of the prostate is a histological finding in almost every set of prostate biopsies, even when there are no signs of clinical prostatitis. This subclinical inflammation can cause PSA elevation. Not the extent of inflammation is of importance, but the disruption of epithelial integrity caused by the inflammatory infiltrate. When confronted with a patient with an elevated PSA level whose prostate biopsies reveal no malignancy but only inflammation, this concept can help in determining the need for quick repeat biopsies.     

Influence of prostatic disease and prostatic manipulations on the concentration of prostate-specific antigen.

We examined the influence of different factors [benign prostatic hyperplasia (BPH), prostatic carcinoma (PCA), organ volume, weight of resected tissue, transurethral catheter] on the serum prostate-specific antigen (PSA) levels in 253 patients with BPH (n = 138; 54%) and PCA (n = 115; 46%). Only in 57.2% of the BPH patients, PSA values were < 4 ng/ml, in 74.6% < 7 ng/ml. In 108 patients with BPH, a transurethral prostatectomy was performed. PSA values correlated significantly with the sonographically determined prostatic volumes and less precisely with the weight of the resected tissue. The PSA concentration per milliliter of prostatic volume was 0.12 ng/ml, per gram of resected tissue it was 0.21 ng/ml. An incidental PCA was found in 12/108 patients (11%). The PSA values were identical with those of the total collective in regard to volume and tissue weight. In 11 patients, we examined possible alterations of the PSA values before and until 24 h after prostatic massage. Only insignificant alterations were seen, a massive increase was not found in any patient. Searching for an absolutely valid 'normal value' appears hardly appropriate. However, the usefulness of PSA is increased when the sonographically determined prostatic volume is included. A rectal examination of the prostate has no influence on the PSA value.     

Comparative analysis of complexed prostate specific antigen, free prostate specific antigen and their ratio in detecting prostate cancer

PURPOSE: We evaluate the diagnostic use of total, free and complexed serum prostate specific antigen (PSA), and their ratios for enhancing the specificity in detecting prostate cancer. MATERIALS AND METHODS: A total of 354 nonconsecutive men undergoing prostate biopsy were eligible for this retrospective and prospective study. Cancer was found in 122 of these 354 men (34%). Receiver operating characteristics curve analyses were used to calculate and compare the performance of total PSA (Hybritech, San Diego California and Bayer, Tarrytown, New York), complexed PSA (Bayer), percent complexed PSA and percent free PSA. In addition, sensitivity and specificity were calculated and compared. RESULTS: The area under the receiver operating characteristics curve was highest for percent free PSA, followed by percent complexed PSA, complexed PSA and the 2 total PSA assays (Hybritech and Bayer). The cutoff value of 3.45 ng./ml. for complexed PSA detected the same number of cancers and resulted in 1 additional false-positive case compared with a Hybritech total PSA threshold of 4.0 ng./ml. At sensitivities of 80% to 95%, there were no significant differences for detection comparing the corresponding specificities between Hybritech total PSA and complexed PSA for all 354 men. Complexed PSA alone did not enhance the overall diagnostic accuracy compared with percent free PSA in the Hybritech total PSA range between 4.01 and 6.00 ng./ml., between 6.01 and 10.00 ng./ml., and between 2.50 and 6.00 ng./ml. At sensitivities of 80% to 95% specificity of percent complexed PSA was almost identical to that of percent free PSA except for the Hybritech total PSA range less than or equal to 4.00 ng./ml. CONCLUSIONS: This study suggests complexed PSA is equivalent to total PSA for the early detection of prostate cancer. Percent free PSA outperforms complexed PSA and percent complexed PSA performed equivalently to percent free PSA in all total PSA ranges analyzed between 2.5 and 10 ng./ml.     

Robustness of free prostate specific antigen measurements to reduce unnecessary biopsies in the 2.6 to 4.0 ng./ml. range

PURPOSE: Prostate specific antigen (PSA) cutoffs lower than 4.0 ng./ml. are being evaluated more frequently but lower PSA cutoffs increase the number of prostatic biopsies. PSA exists in several forms free and complexed to proteins. Percent free PSA is lower in men with prostate cancer. Accordingly, free PSA and complexed PSA have been used to distinguish between cancer and benign disease in the diagnostic gray zone of 4 to 10 ng./ml. to eliminate unnecessary biopsies. There are limited data on the robustness of free PSA measurements in the 2.6 to 4.0 ng./ml. total PSA range. MATERIALS AND METHODS: We evaluated percent free PSA measurements to discriminate between cancer and benign conditions in 965 consecutive volunteers in a prostate cancer screening study who underwent prostatic biopsy for a PSA of 2.6 to 4.0 ng./ml. and had benign digital rectal examination. RESULTS: Overall 25% of men had cancer detected. A 25% free PSA cutoff detected 85% of cancers and avoided 19% of negative (cancer-free) biopsies, while a 30% free PSA cutoff detected 93% of cancers and avoided only 9% of negative biopsies. Of those men who underwent radical prostatectomy 132 (80%) had pathologically organ confined tumors. Only 5% of these tumors fulfilled the published pathological criteria for possibly clinically unimportant tumors. CONCLUSIONS: Percent free PSA provides risk assessment but does not eliminate many unnecessary prostatic biopsies while maintaining a high sensitivity in the narrow total PSA range of 2.6 to 4.0 ng./ml.     

Intraepithelial prostatic neoplasia

44 patients seeked medical advice for low urinary symptoms. Their examination consisted of digital rectal investigation, test for prostate-specific antigen (PSA) in the serum, transurethral ultrasonic investigation, fine needle multifocal biopsy of the prostate. Three groups were identified by the PSA levels. 7 patients of group 1 had PSA up to 6 ng/ml. Cancer was diagnosed in 3 of them, prostatic intraepithelial neoplasia (PIN) in 4 patients. 16 patients of group 2 had PSA within 7-10 ng/ml. In this group only 1 patient had cancer, the rest 15 had PIN. 21 patients of group 3 with PSA at least 10 ng/ml had cancer, benign prostatic hyperplasia, PIN (12, 2 and 7 patients, respectively). 3 patients with high-grade PIN and PSA above 10 ng/ml in 6 months were diagnosed to have adenocarcinoma, in 6 such patients signs of dysplasia disappeared after antiandrogenic therapy. Further investigations on diagnosis and treatment of PIN are desirable.