Prostate specific antigen and benign prostatic hyperplasia

Benign prostatic hyperplasia is a common condition in males over 50 years, but prostate cancer can develop in the same population. Prostate specific antigen, the best marker for prostate cancer, is also produced by benign epithelial cells, and there is an overlapping phenomenon between both conditions. The better we understand the relationships between benign prostatic hyperplasia and prostate specific antigen, the higher will be the discrimination power of prostate specific antigen measurement as a marker for prostate cancer. Our scope includes a review of the latest published material to date on this subject.     

Prostate specific antigen density for discriminating prostate cancer from benign prostatic hyperplasia in the gray zone of prostate-specific antigen.

Serum prostate specific antigen (PSA) is currently the best blood marker for prostate cancer. However, low specificity for detection of prostate cancer, especially in the gray zone of PSA, is a problem. We evaluated the clinical significance of PSA density (PSAD) in gray zone PSA cases with conversion of serum PSA to a Stanford reference value. In a series of histologically confirmed 63 benign prostatic hyperplasia (BPH) patients and 234 prostate cancer patients, 36 BPH patients and 25 prostate cancer patients had gray zone PSA levels. Serum PSA was measured with the Markit-F or Markit-M PA assay. All data were converted to Stanford reference values. We used transabdominal ultrasound to determine prostate volume. PSAD was determined as the serum PSA/prostate volume ratio. The mean PSA values for BPH and prostate cancer were 6.42 +/- 1.80 and 7.80 +/- 2.15 ng/ml (p = 0.0116), respectively, and prostate volume was 33.4 +/- 14.1 ml and 17.1 +/- 8.2 ml, respectively (p < 0.0001). The mean PSAD for prostate cancer was 0.572 +/- 0.363 while that for BPH was 0.218 +/- 0.085 (p = 0.0001). Cut-off values with sensitivity > 90% were 0.218 for PSAD and 30 ml for prostate volume. At these cut-off values, specificity reached 56% for each marker. In discriminating prostate cancer from BPH in the gray zone of PSA, PSAD demonstrated better performance than PSA.     

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.     

前列腺体积对前列腺特异抗原的影响

目的：研究前列腺特异怕（ＰＳＡ）与前列腺增生腺体体积的关系及其在前列腺癌（ＰＣａ）诊断中的价值。方法：７５例前列腺增生症（ＢＰＨ）患者根据其ＰＳＡ〉或≤４μｇ／Ｌ分为两组,另有２５例ＰＣａ患者,术后用放射免疫法测定血清ＰＳＡ《所有患者经Ｂ超测出前列腺体积,用ｔ检验和相关分析研究各组间的差异及相关性。结果：ＰＳＡ〉４μｇ／Ｌ的ＢＰＨ较之ＰＳＡ≤４μｇ／Ｌ者,腺体体积显著增大且ＰＳＡ和ＰＳＡ密度（ＰＳ     

Local staging of prostate cancer by tumor volume, prostate-specific antigen, and transrectal ultrasound.

Conventional methods of staging prostate tumors are highly inaccurate. To improve clinical staging, prostate-specific antigen (PSA) levels (> 10 ng/mL), sonographic tumor volume (> 3 cc), maximum tumor diameter, length of capsular tumor abutment, and overall impression of capsular irregularity suggesting periprostatic tumor spread were assessed in 29 men prior to undergoing radical prostatectomy for clinically localized tumor. After surgery, 18 men had tumor confined to the prostate, while 11 men had histologic evidence of extracapsular disease. Analysis of the parameters measured showed these were the most helpful factors in predicting the presence of extracapsular disease. However, the positive and negative predictive values were only 70 to 90 percent. Therefore, the clinical usefulness of any one measurement alone in determining treatment for the individual patient is limited. However, combining these parameters yields an improved prediction of extracapsular disease. All 6 patients with PSA < 10 ng/mL, tumor volume < 3 cc, and no capsular irregularity on ultrasound had localized disease (neg. predictive value = 100%), while all 7 patients who had more than one of these parameters had extracapsular disease (pos. predictive value = 100%). Thus, using the factors in combination may provide more accurate staging and thereby help in counseling patients regarding therapy.     

良性前列腺增生症发生急性尿潴留的相关因素分析

目的:应用临床常用指标,探讨BPH发生急性尿潴留(AUR)的相关因素。方法:回顾分析538例BPH患者相关资料。分为曾发生AUR(A组)260例,从未发生AUR(B组)278例。分别比较两组间在年龄(AGE)、前列腺总体积(PV)、前列腺移行区体积(TZV)、移行区指数(TZI)和前列腺特异抗原(PSA)、游离前列腺特异抗原(F-PSA)、游离与总前列腺特异抗原比值(F/T-PSA)等指标上的差异性。结果:A组平均PV、TZV和PSA值皆明显高于B组,上述3个指标在两两组间差异有统计学意义,且PSA与PV、TZV均有正相关性。结论:PV、TZV及PSA可作为预测BPH发生AUR的良好指标。     

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.     

Increased discrimination between benign prostatic hyperplasia and prostate cancer with equimolar total prostate specific antigen measurement

Although prostate specific antigen (PSA) is widely used in the discrimination of benign prostatic hyperplasia (BPH) and prostate cancer, its diagnostic value is controversial due to an appreciable false positive rate. In the present study, we compared a recently introduced assay method, equimolar PSA measurement, to non-equimolar PSA measurement and also determined the diagnostic value of percent free PSA with changing total PSA (tPSA) measurements. Between April 1999 and December 2001, the sera of 61 patients with BPH and 41 with prostate cancer were examined. Total PSA and free PSA was determined using the Immulite 2000 assay system, whereas equimolar tPSA measurement was performed using Bayer PSA Q for the Chiron ACS 180 system. Comparative analysis of the two different assays revealed better diagnostic sensitivity and specificity values for equimolar tPSA measurement, which in turn would have led to 10% of the patients avoiding an unnecessary biopsy. Additionally, percent free PSA with the changing denominator of tPSA assays showed that the free PSA/equimolar tPSA ratio was the best tumor marker among the studied forms of PSA. It was concluded that equimolar tPSA measurement using recombinant Fab fragments is superior to the classical measurements with monoclonal antibodies, and that the use of percent free PSA with the equimolarly measured tPSA has better sensitivity and specificity in the discrimination of benign and malignant diseases of the prostate.     

The relationship of prostate specific antigen levels and residual tumor volume in stage A prostate cancer.

Preoperative serum prostate specific antigen correlates well with morphometrically determined prostate tumor volume in prostatectomy specimens. However, since prostate specific antigen is produced by hyperplastic as well as malignant prostatic epithelium, the contribution of hyperplastic epithelium (benign prostatic hyperplasia) to serum prostate specific antigen interferes with the ability of serum prostate specific antigen to predict tumor volume in individual patients. We wondered if the removal of benign prostatic hyperplasia tissue would increase the correlation between prostate specific antigen and tumor volume, and, thus, make prostate specific antigen a more accurate predictor of residual cancer volume after transurethral resection of the prostate. A total of 67 patients with clinical stage A cancer underwent radical retropubic prostatectomy (22, or 33%, with stage A1 and 45, or 67%, with stage A2 disease), and had pre-radical prostatectomy measurement of serum prostate specific antigen and morphometric determination of residual cancer volume in the radical prostatectomy specimen. The correlation between serum prostate specific antigen and residual cancer volume for all 67 patients was 0.66, and for stages A1 and A2 disease it was 0.64 and 0.70, respectively. All stage A1 cancer patients with a serum prostate specific antigen value of 1 ng./ml. or less had residual tumor volumes of less than 0.5 cc and all stage A cancer patients with a serum prostate specific antigen value of more than 10 ng./ml. had residual tumor volumes of greater than 0.5 cc. Of the patients 51% had levels of 1 to 10 ng./ml. and serum prostate specific antigen was not useful to predict residual tumor volume in this group. Serum prostate specific antigen measurements may be helpful in stage A1 cancer patients with levels of 1 ng./ml. or less, or greater than 10 ng./ml. in choosing the most appropriate therapy.     

Change in International Prostate Symptom Score, prostrate-specific antigen and prostate volume in patients with benign prostatic hyperplasia followed longitudinally

OBJECTIVE: The natural history of benign prostatic hyperplasia (BPH) in Japan resembles Western studies in that symptoms worsen, improve or stabilize in equal proportions of patients. We sought to determine if this pattern persisted in men seeking care at a urology referral center and if worsening of symptoms was due to increase in prostate volume (PV). METHODS: We reviewed the records of all BPH patients who attended the Urology Clinic of Sapporo Medical University Hospital, during December 2003 and June 2004 with the inclusion criterion that they have at least two PV and lower urinary tract symptoms measurements using the International Prostate Symptom Score (IPSS). Patients who had prostate cancer or who underwent hormone therapy or prostate surgery between the two visits were excluded. Correlation (Spearman's rank) was used to assess interrelationships among variables at baseline and follow up; the strength of association between change in IPSS and change in PV were modeled by multiple linear regression. RESULTS: Sixty-seven patients were eligible. Baseline PV correlated with residual urine volume (r = 0.37, P < 0.05) and prostate-specific antigen (PSA; r = 0.65, P < 0.001) but not IPSS (r =-0.16). PV increased in 46 (70%) men, remained the same in 10 and decreased in 11; in the former group, the mean prostate enlargement generally increased as baseline PV increased. In multiple linear regression models that included baseline IPSS, correlation between change in IPSS and change in PV was 0.47 (P = 0.05) based on 25 patients with measures at concurrent visits. Change in PV was also correlated with change in quality of life score (0.46, P = 0.02) but not with change in PSA (r = 0.38, P = 0.07, maximum flow rate (-0.24) or residual urine volume (-0.06). CONCLUSIONS: IPSS were not correlated with any laboratory measure of urinary function at baseline; however, change in IPSS was associated with change in PV. PV was also moderately correlated to PSA levels and residual urine volume at baseline.     

Prostate specific antigen bounce phenomenon after external beam radiation for clinically localized prostate cancer

PURPOSE: We characterize the prostate-specific antigen (PSA) bounce in patients who underwent external beam radiation therapy for prostate cancer and correlate the PSA bounce with the development of biochemical disease progression. MATERIALS AND METHODS: In this study 964 patients received full dose radiation therapy alone. Followup PSA values were obtained 3 months after completion of radiotherapy and every 3 to 6 months thereafter. Median followup of the entire study group was 48 months. All time intervals were calculated from the completion date of radiation therapy. PSA bounce was defined as an initial increase in serum PSA of at least 0.5 ng./ml., followed by a decrease to pre-bounce baseline serum PSA values no more than 60 months after external beam radiation therapy. RESULTS: Of the 964 patients 119 (12%) had a PSA bounce. PSA bounce was unrelated to age, race, pretreatment PSA, Gleason score, clinical T stage or radiation dose. Mean time to PSA bounce was 9 months from the time of therapy. The respective 1 and 5-year biochemical disease-free survival rates were 100% and 82.1% for patients with PSA bounce and 93.9% and 57.7% for those without PSA bounce (p = 0.0001). CONCLUSIONS: Of men with prostate cancer treated with external beam radiation therapy 12% experienced a transient increase in PSA (PSA bounce) followed by a return to pre-bounce levels after radiation. The PSA bounce phenomenon was not predictive of time to biochemical recurrence.     

Prostate specific antigen only progression of prostate cancer

PURPOSE: Introduction of the prostate specific antigen (PSA) serum marker for prostate cancer and the subsequent PSA era from 1988 to the present have dramatically altered the diagnosis of the disease. The early to mid 1990s diagnosis boom resulted in a huge increase in clinically localized and early stage disease treatments. Radical prostatectomy rates increased from 17.4 to 54.6/100,000 between 1988 and 1992, and age adjusted rates increased 2 to 4-fold for men in the fifth and sixth decades of life. Since the late 1990s clinicians have been seeing the effects of this diagnosis and localized treatment boom, in that many men each year are experiencing PSA only disease recurrence. Given that the majority are relatively young and otherwise healthy, treatment of PSA only recurrence requires approaches that not only improve survival, but also preserve quality of life. A comprehensive overview of the definition of PSA only recurrence, staging controversies and the wide variety of treatments to be considered is provided. MATERIALS AND METHODS: A literature review and overview of the topic of PSA only recurrence after prior clinically localized prostate cancer treatment were performed. RESULTS: For radical prostatectomy cases PSA only recurrence is broadly defined as any elevation of PSA postoperatively. For radiation treated patients the 1997 American Society for Therapeutic Radiology and Oncology guidelines specify 3 consecutive elevations of PSA after posttreatment PSA nadir is achieved. As localized treatment series in the PSA era have matured, and database and statistical support have improved, a number of useful models to predict PSA only recurrence have emerged. These models are based on traditional prognostic markers, such as pretreatment PSA, and grade and stage of disease as well as emerging molecular and cellular biomarkers. Although bone scans and pelvic computerized tomography are commonly used for re-staging at PSA only recurrence, recent study suggests that their value is limited unless PSA recurrence exceeds 30 to 40 ng./ml. 111Indium capromab pendetide radionuclide scan, which has been approved for radical prostatectomy PSA only recurrence, may be helpful to determine cases best suited for salvage radiotherapy versus systemic hormonal therapy, although more study is needed. Treatment of PSA only recurrence is divided into 2 main categories of salvage local treatments and systemic therapy. The principal dilemma is the inability to determine definitively whether PSA only recurrence is solely due to local progression or distant micrometastases. External beam radiation is the main local salvage treatment for radical prostatectomy recurrence, and cryotherapy, salvage prostatectomy and salvage brachytherapy are options for radiation recurrence. Proper patient selection is critical to the success of all salvage local treatments. Traditional hormonal therapy is the mainstay of systemic treatment for PSA only recurrence, although nontraditional approaches, such as intermittent and low dose hormonal therapy, are under study. Emerging chemopreventive agents, such as vitamins, minerals and other supplements, may have a future role in treatment. CONCLUSIONS: PSA only recurrence after prior local prostate cancer treatment remains a common problem facing clinicians.     

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.     

Serum prostate specific antigen levels during hyperthermia treatment of benign prostatic hyperplasia.

To understand better the tissue and cell changes occurring in the human prostate as a reaction to heat, we used circulating prostate specific antigen as a marker to detect cell injury. The prostate in 18 patients with benign prostatic hyperplasia was heated to 42 +/- 1.5C with local microwaves at 915 MHz. Each treatment sessions lasted 1 hour and the patients underwent 5 treatment sessions. A total of 90 treatment sessions was performed among 18 patients. No significant difference was observed between pre-treatment and post-treatment serum prostate specific antigen levels. We conclude that local hyperthermia is an atraumatic treatment modality that does not exert its effect on the hyperplastic prostate via a cytotoxic insult to prostate epithelial tissues.