Intra-individual variation of serum prostate specific antigen levels in men with benign prostate biopsies

OBJECTIVE: To determine the intra-individual (physiological) variation of prostate-specific antigen (PSA) measurements in men after a benign prostatic biopsy. PATIENTS AND METHODS: Sixty-four men were prospectively assessed, all of whom had a benign prostatic biopsy within the preceding 13 months. The degree of intra-individual variability was established by calculating the coefficient of variation on four PSA levels obtained from each patient weekly over a month. RESULTS: Six patients were subsequently diagnosed with prostate cancer and their data are presented separately. In the remaining 58 patients the median (range) individual mean PSA value was 6.3 (0.5-34.1) ng/mL. The median (range) coefficient of variation within the group was 9.5 (2.4-76.1)%. There was a clear linear relationship between mean PSA level and the standard deviation. CONCLUSION: In 48 of the 63 patients analysed, the coefficient of variation for serum PSA values in the group as a whole was greater than the variation claimed for the assay technique. The significance of the linear relationship between PSA and the standard deviation is discussed, with particular reference to those men who had a benign prostate biopsy.     

血清PSA、f-PSAR与前列腺重量相关性研究

目的：探讨前列腺增生症（ＢＰＨ）人群中前列腺重量（ＰＷ）与血清前列划抗原（ＰＳＡ）、血清液离前腺特异抗原百分率（ｆ－ＰＳＡＲ）的相关性,方法：术前测定１４６例ＢＰＨ患者血清ＰＳＡ〈其中５１例测定了血清游离前列腺特异抗原值,对血清ＰＳＡ〉１０μｇ／Ｌ患者行前列腺穿刺活检以排除前列腺癌,术后对前列腺手术标本进行称重,并按〈２５ｇ,２５￣５０ｇ、５１￣７５ｇ、〉７５ｇ分为４组,均经病理证实为ＢＰＨ,对忾     

Correlation between serum prostate specific antigen and prostate volume in Taiwanese men with biopsy proven benign prostatic hyperplasia

PURPOSE: We studied the correlation between serum prostate specific antigen and the volume of different zones of the prostate in Taiwanese men with biopsy proven benign prostatic hyperplasia. MATERIALS AND METHODS: A total of 233 patients with a mean age of 71.4 years (range 42 to 89), serum prostate specific antigen less than 10 ng/ml and pathologically confirmed benign prostatic hyperplasia were enrolled in this study. Total prostate and transitional zone volumes were measured with transrectal ultrasonography. Peripheral zone volume was determined by subtracting transitional zone volume from total prostate volume. Correlations between patient age, total serum prostate specific antigen and the volume of each prostate zone were analyzed with the Pearson correlation coefficient. A linear regression model was used to determine the relationship between prostate specific antigen and prostate volume. The prostate specific antigen-prostate volume relationship in our patients was compared with published data on white and Japanese men. RESULTS: Age did not significantly correlate with serum prostate specific antigen and prostate volume. Serum prostate specific antigen significantly correlated with the volume of each prostate zone. After log transformation the Pearson correlation coefficient between total prostate specific antigen and the volume of the whole prostate gland, the transitional zone and the peripheral zone were 0.369, 0.377 and 0.272, respectively (p <0.001). Taiwanese men had lower prostate volume per unit prostate specific antigen comparing with white men, while the prostate specific antigen-total prostate volume relationship between Taiwanese and Japanese men was similar. CONCLUSIONS: In Taiwanese men with biopsy proven benign prostatic hyperplasia the volume of each prostate zone has significantly correlates with serum prostate specific antigen. The prostate specific antigen-total prostate volume relationship in Taiwanese men is different from that in white men. However, the prostate specific antigen-total prostate volume relationship between Taiwanese and Japanese men is similar.     

Serum free prostate specific antigen: Isoenzymes in benign hyperplasia and cancer of the prostate

Prostate specific antigen (PSA) in serum of patients with benign prostatic hyperplasia (BPH) or prostate cancer (P-CA) not bound to α-1-antichymotrypsin (ACT) was analyzed by chromatofocusing. The procedure allowed the simultaneous separation of complexed and free PSA and the fractionation of the free PSA fraction into several isoenzymes. The detection of the isoenzymes was strongly dependent on the combination of antibodies introduced in the applied commercially available immunoassays (Cobas® Core, Delfia®). Isoenzymes in sera of patients with benign prostatic hyperplasia were mainly situated in the pI range of 6.6 to 7.3. Isoenzymes in sera of prostate cancer patients or in PSA from LNCAP cells were mainly situated in the pI range 7.0 to 8.3. Neuraminidase treatment of the sera shifted the isoelectric points of all three sources towards more basic pHs. An irregular glycosylation process in the dysplastic cells of the prostate is suggested to be the cause for the shift of the isoelectric points. The difference of isoenzyme distribution along the pH axis is discussed as a diagnostic tool to differentiate between BPH and P-CA. © 1995 Wiley-Liss, Inc.     

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.     

Inactive free : total prostate specific antigen ratios in ejaculate from men with suspected and known prostate cancer, compared with young control men

OBJECTIVE: To measure free : total prostate specific antigen (PSA) ratios in ejaculate from men with suspected and known prostate cancer, and in young control men, to determine if this ratio might be useful in discriminating benign from malignant prostatic conditions. Patients, subjects and methods Forty-seven men with prostate cancer (positive biopsies), 52 men with suspected prostate cancer but who had negative biopsies and 28 young men (< 30 years old) and with no family history of cancer, provided either a single ejaculate specimen (total 59) or multiple specimens (total 193) on subsequent occasions. Free and total PSA were measured using appropriate assays. All specimens were diluted in a PSA-negative female serum pool. RESULTS: The median free : total PSA ratios were 0.76-0.81 among the patient groups and control men, and there was no statistical difference between the groups. These data presumably only reflect the inactive component of free PSA, given that any alpha2-macroglobulin or alpha1-antichymotrypsin in the assay serum diluent was likely to have bound the active free PSA component in these samples. Similar results were obtained from those providing single and multiple samples, suggesting that a single specimen is sufficient to reflect the seminal plasma free : total PSA ratio over that period. There was no relationship between seminal plasma free : total PSA ratio and age for the controls or the positive biopsy group, although there was a negative relationship (i.e. a decline with age) that almost reached significance in those with negative biopsies (P = 0.058, R2 = 0.07). CONCLUSIONS: This is the first report of free : total PSA ratios in the ejaculate of men with suspected and known prostate cancer compared with young control men. Although no significant changes were detected in the free : total PSA ratios in ejaculate, these results may be confounded by differences in ratios with age, as is the case for serum PSA or different molecular forms of PSA. Indeed, these data suggest that a large proportion of free PSA in seminal plasma may be inactive. Further studies are needed to determine the potential utility of measuring free : total PSA, or other candidate markers, in ejaculate to better discriminate benign from malignant prostate disease.     

Relationship between serum prostate specific antigen and histological prostatitis in patients with benign prostatic hyperplasia

The relationship between the serum values of prostate specific antigen (PSA) and the extent of histological prostatitis was investigated in 42 patients undergoing transurethral resection of the prostate for benign hyperplasia (BPH) without clinical evidence of prostatitis. Histological prostatitis was divided into three groups: acute, chronic-active, and chronic-inactive inflammation. The extent of histological prostatitis was expressed as the number of prostatic acinar and ductal glands with inflammatory infiltrate per total number of glands (%). The serum PSA values significantly correlated with the extent of acute and chronic-active prostatitis (correlation coefficient r = 0.765 and 0.656, P < 0.01). A relationship between PSA values and the extent of chronic-inactive prostatitis was not found. In the immunohistochemical study, prostatic epithelial cells with acute and chronic-active inflammation showed negative staining for PSA antigen. These results indicate that histological acute and chronic-active prostatitis is considered an important factor for inducing the high increase in serum PSA values via the leak phenomenon. © 1994 Wiley-Liss, Inc.     

Influence of prostate volume and percent free prostate specific antigen on prostate cancer detection in men with a total prostate specific antigen of 2.6 to 10.0 ng/ml

PURPOSE: Percent free prostate specific antigen and prostate specific antigen density have been independently shown to increase the specificity of prostate cancer screening in men with prostate specific antigen levels between 4.1 and 10.0 ng/ml. Recent data suggest the total prostate specific antigen cutoff for performing a biopsy should be 2.6 ng/ml. We assessed the influence of percent free prostate specific antigen and prostate volume on cancer detection in men with a prostate specific antigen between 2.6 and 10.0 ng/ml. MATERIALS AND METHODS: From 1991 to 2005 all transrectal ultrasound guided prostate biopsies (5,587) for abnormal digital rectal examination and/or increased age specific prostate specific antigen were evaluated. A total of 1,072 patients with a prostate specific antigen between 2.6 and 10.0 ng/ml and any percent free prostate specific antigen were included in study. The cancer detection rate was calculated for each percent free prostate specific antigen/volume stratum. RESULTS: Prostate cancer was detected in 296 patients (27.6%). The mean age and prostate specific antigen of the patients with benign pathology and prostate cancer were similar. Mean percent free prostate specific antigen was 17.5% and 14.1% (p>0.05), and the mean volume was 62.0 and 46.0 cc (p=0.001), respectively. The strongest risk factors for a positive biopsy were percent free prostate specific antigen (odds ratio 0.004, p<0.001), volume (OR 0.977, p<0.001) and digital rectal examination (OR 1.765, p=0.007), but not total prostate specific antigen (p=0.303). When stratified by volume and percent free prostate specific antigen, distinct risk groups were identified. The probability of detecting cancer inversely correlated with prostate volume and percent free prostate specific antigen. CONCLUSIONS: In men with prostate specific antigen levels between 2.6 and 10.0 ng/ml, the probability of detecting cancer was inversely proportional to prostate volume and percent free prostate specific antigen. This table may assist in predicting patient risk for harboring prostate cancer.     

Prostate specific antigen measurements after minimally invasive surgery of the prostate in men with benign prostatic hypertrophy

There is a trend of minimally invasive surgery in the treatment of benign prostatic hypertrophy (BPH). Studies have examined levels of prostate specific antigen (PSA) in patients after open prostatectomy or transurethral resection of prostate (TURP) and noted reset of PSA to lower values after surgery. We reviewed PSA levels in patients after minimally invasive procedures to determine if levels were reset. There were 120 patients (age 45-70) enrolled in the study. Fifty patients underwent laser ablation, 20 patients had electrovaporization (TVP) and 50 patients underwent TURP. PSA measurements were obtained prior to and after surgical procedures in a three-year follow-up. Mean pre-operative PSA was 2.8 (+/-0.34) ng/ml for laser cohort, 3.2 (+/-0.31) ng/ml for the TURP group and 2.3 (+/-0.42) ng/ml for TVP patients (P=0.33). At 1 y follow-up, mean PSA decreased 32% for laser patients, 46% for the TURP cohort and 8% for TVP group. The largest mean decrease in PSA velocity was-1.5 (+/-0.31) ng/ml per y for TURP followed by 0.9 (+/-0.29) ng/ml per y for laser patients and-0.1 (s.d.+/-1.2) ng/ml per y for TVP group in y 1. The TURP group maintained the largest decrease in PSA velocity in y 2,-0.6 (+/-0.26) ng/ml per y. Three patients (2-TURP, 1-TVP) were diagnosed with prostate cancer during follow-up. In conclusion, serum PSA levels were reset at lower levels following different surgical interventions. This lower level of PSA remained decreased for 2 y post-procedure. Urologists should be cognizant of this reset level and monitor PSA levels for possible increases to screen for prostate cancer in this patient population. Prostate Cancer and Prostatic Diseases (2000) 3, 200-202     

Radiotherapy for men with isolated increase in serum prostate specific antigen after radical prostatectomy

PURPOSE: In this retrospective study we determined the results of salvage external beam radiation therapy (RT) to the prostate bed for isolated increase of serum prostate specific antigen (PSA) after radical prostatectomy. MATERIALS AND METHODS: A total of 60 patients underwent RT for PSA failure after radical prostatectomy from 1993 to 1999. Median followup was 51 months. Biochemical disease-free survival (bDFS) with a serum PSA of 0.3 ng/ml or less was estimated using the Kaplan-Meier method. Potential prognostic factors were evaluated for significant associations with bDFS. RESULTS: Median PSA before RT was 0.69 ng/ml. Median radiation dose was 64.8 Gy. The 5-year actuarial bDFS was 45%. There were 32 patients with a minimum followup of 4 years (median 73 months) who experienced a 5-year bDFS rate of 43%. PSA before RT (p = 0.016), RT dose (p = 0.026), surgical margin involvement (p = 0.017) and Gleason score (p = 0.018) were identified as prognostic factors for bDFS. A significant association with bDFS was present at 5 years of 65%, 34% and 0% for PSA before RT less than 0.6, 0.6 to 1.2, and greater than 1.2 ng/ml, respectively (p = 0.036). Patients with PSA before RT less than 0.6 ng/ml and total RT dose greater than 64.8 Gy had improved bDFS at 5 years compared to all others (77% vs 32%, p = 0.04). Of 60 patients 3 (5%) experienced chronic grade 3 toxicity. CONCLUSIONS: Optimal benefit from salvage RT was achieved in patients with a PSA less than 0.6 ng/ml and doses of RT greater than 64.8 Gy. Early treatment with a sufficiently high dose of RT maximizes the potential for salvage.     

The value of the measurement of serum prostate specific antigen in patients with benign prostatic hyperplasia and untreated prostate cancer

Serum prostate specific antigen (PSA) levels were measured in 139 patients with benign prostatic hyperplasia (BPH) and in 88 patients with prostate cancer who were managed by deferred treatment. Acute urinary retention and large prostate glands tended to be associated with high PSA levels, but at levels greater than 10 ng/ml there was a significant risk of carcinoma being found on subsequent histological examination. The risk of progression of untreated prostate cancer was associated with levels of PSA greater than 20 ng/ml and with a high rate of change of PSA level. The value of measuring PSA in these patients is discussed.     

前列腺活检对血清T-PSA F-PSA及F/T比值的影响

目的 :研究经直肠前列腺穿刺活检对血清总前列腺特异抗原 (T PSA)、游离前列腺特异抗原 (F PSA)及游离 /总前列腺特异抗原 (F/T)比值的影响。方法 :对 36例前列腺活检示良性病变的患者 ,分别于活检前及活检后 0 .5h、1周、30d检测T PSA、F PSA值 ,并计算F/T比值。结果 :活检前及活检后 0 .5h、1周、30d患者血清T PSA分别为 (11.76± 7.82 ) μg/L、(36 .90± 2 4 .76 ) μg/L、(2 4 .36± 16 .18) μg/L和 (12 .2 1± 6 .4 9) μg/L ;F PSA分别为 (2 .4 1± 0 .96 ) μg/L、(2 5 .14± 12 .5 6 ) μg/L、(4 .0 2± 1.90 ) μg/L和 (2 .6 1± 0 .87) μg/L ;F/T比值分别为 0 .2 1± 0 .0 6、0 .6 8± 0 .18、0 .15± 0 .0 4和 0 .2 2± 0 .0 5。与活检前相比 ,活检后 0 .5h、1周T PSA、F PSA值显著升高 (P <0 .0 1、P <0 .0 5 ) ;F/T比值活检后 0 .5h显著升高 (P <0 .0 1) ,活检后 1周时显著降低 (P <0 .0 5 ) ;活检后 30d时 ,以上指标与活检前相比 ,差异均无统计学意义 (均P >0 .0 5 )。结论 :前列腺穿刺活检 ,会导致血清T PSA、F PSA及F/T比值的显著升高 ,临床上要获得有意义的PSA的指标 ,最好在活检 30d后检测     

Performance of prostate‐specific antigen mass in estimation of prostate volume in Japanese men with benign prostate hyperplasia

Objectives: Obese men with benign prostate hyperplasia might have lower serum prostate‐specific antigen because of hemodilution, resulting in underestimation of total prostate volume by serum prostate‐specific antigen. The aim of this study was to compare the performance of prostate‐specific antigen mass as the absolute amount of prostate‐specific antigen protein secreted into circulation with that of serum prostate‐specific antigen in the prediction of total prostate volume. Methods: A total of 1517 men with serum prostate‐specific antigen up to 10 ng/mL, including 1425 with biopsy‐proven benign prostate hyperplasia, were enrolled in this study. Height and weight were used to estimate body mass index, body surface area and plasma volume. Prostate‐specific antigen mass was calculated as serum prostate‐specific antigen multiplied by plasma volume. The association between serum prostate‐specific antigen or prostate‐specific antigen mass and transrectal ultrasound‐measured total prostate volume were evaluated by Pearson's correlation coefficient (Υ), linear regression analyses and receiver operating characteristic curves. Results: Serum prostate‐specific antigen had an inverse relationship with plasma volume, decreasing as plasma volume increased, after adjustment of total prostate volume. Larger total prostate volume per serum prostate‐specific antigen was found in men with higher body mass index or plasma volume. Among all participants, the correlation (Υ = 0.456) between prostate‐specific antigen mass and total prostate volume was apparently stronger than that (Υ = 0.442) between serum prostate‐specific antigen and total prostate volume. Prostate‐specific antigen mass outperformed serum prostate‐specific antigen at estimating total prostate volume cut‐off values of 30 and 40 mL. These findings were more significant in men aged ≥60 years. Conclusions: Prostate‐specific antigen mass performs better than serum prostate‐specific antigen in estimating TPV, especially in men aged ≥60 years.     

Prostatic acid phosphatase, beta-glucuronidase and prostate specific antigen assays in fine needle aspirates from benign and malignant prostates.

Enzymatic assays for tartrate-sensitive acid phosphatase and beta-glucuronidase, and radio-immunoassay for prostate-specific antigen, were modified for application to fine-needle aspirate samples from benign and malignant human prostates. When compared to samples from benign prostates, the ratio of acid phosphatase to beta-glucuronidase activities was significantly decreased in needle aspirates from malignant prostates. Prostate-specific antigen values in the aspirates did not correlate with malignancy.     

"PSA-itis": knowledge of serum prostate specific antigen and other causes of anxiety in men with metaststic prostate cancer

PURPOSE: High or increasing prostatic specific antigen (PSA) levels may be a source of anxiety in patients with metastatic prostate cancer. MATERIALS AND METHODS: Patients with metastatic prostate cancer completed questionnaires, including the Prostate Cancer Specific Quality of Life Instrument, Hospital Anxiety and Depression Scale, and a questionnaire to assess the impact of the knowledge of PSA levels on anxiety. These were completed at home more than 3 days before or after a clinic appointment and returned by mail. Patient medical history was obtained from the record. RESULTS: Of the 65 patients who consented to the study 52 returned the completed questionnaires. Median age was 70 years (range 55 to 86) and median time since diagnosis was 53 months. Of the patients 81% had hormone resistant disease. Most reported good overall quality of life with a median Prostate Cancer Specific Quality of Life Instrument score of 93 (maximum 100). Of the patients 77% indicated that PSA levels were one of the ways and 44% indicated they were the only way that they knew whether disease was progressing. When asked to rate preferences for treatment outcome, 25% of the men rated decreasing PSA and worse physical symptoms above increasing PSA and better physical symptoms. If measurement of PSA levels ceased, 52% of patients would believe that their doctor was giving up on them and only 1 would be relieved. Before receiving PSA results 76% reported some level of anxiety and 15% reported extreme anxiety. CONCLUSIONS: PSA related anxiety represents a substantial problem in patients with metastatic prostate cancer.     

血清PSA、PSAD和PSAT在前列腺穿刺活检中的意义

目的探讨血清前列腺特异性抗原(PSA)、前列腺特异性抗原密度(PSAD)和前列腺移行带特异性抗原密度(PSAT)在前列腺穿刺活检中的意义。方法对192例患者行前列腺穿刺活检,其中PSA≥4ng/ml者184例,PSA<4ng/ml且直肠指诊及经直肠B超有阳性发现者8例。对PSA、PSAD和PSAT与前列腺穿刺活检的关系进行分析。结果192例患者中经前列腺穿刺诊断为前列腺癌(PCa)100例,活检阳性率52.1%,其中8例PSA<4ng/ml者中,活检结果为前列腺横纹肌肉瘤1例,良性前列腺增生7例;93例PSA>20ng/ml者中80例为PCa,活检阳性率86.0%;91例PSA4~20ng/ml者中19例为PCa,活检阳性率20.9%。血清PSA4~20ng/ml患者,PSAD>0.10或PSAT>0.10时,敏感性均为100%,特异性为11.1%或4.2%,阳性预测值为22.9%或21.6%,可避免8.8%(8/91)或3.3%(3/91)阴性穿刺结果。血清PSA4~20ng/ml时,前列腺穿刺阳性组和阴性组PSA分别为(13.2±4.7)和(11.4±4.6)ng/ml(P>0.05);PSAD分别为0.36±0.18和0.19±0.09(P=0.001);PSAT分别为0.67±0.36和0.32±0.18(P=0.000)。血清PSA、PSAD和PSAT的ROC曲线下面积分别为0.613、0.810和0.833,PSAD和PSAT的ROC曲线下面积与PSA比较,差异均有统计学意义(P<0.05)。结论PSA>20ng/ml时应做前列腺穿刺活检;PSA4~20ng/ml时,PSAD和PSAT对预测患者是否行前列腺穿刺活检有较大帮助。