The effect of finasteride on prostate-specific antigen in men with benign prostatic hyperplasia

Finasteride is a specific 5-α-reductase inhibitor that has been shown to reduce prostate size and decrease serum levels of prostate specific antigen (PSA). Among men who received finasteride (5 mg/day) for 12 months in North American clinical trials and in whom prostate cancer was not diagnosed the median percentage change in PSA was ?50% (5–95% range: ?81% to + 20%). At baseline 72% had PSA ? 4.0 ng/ml and 93% had PSA ? 10.0 ng/ml. After 12 months on finasteride, 75% had PSA ? 2.0 ng/ml and 95% had PSA ? 5.0 ng/ml. Thus, the proportion of BPH patients with PSA levels of 2.0 ng/ml and 5.0 ng/ml after 12 months of treatment was comparable to the proportion with pretreatment PSA levels of 4.0 ng/ml and 10.0 ng/ml. Among the 10 men in these trials subsequently diagnosed with prostate cancer while on long-term finasteride therapy (5 mg/day), the median percentage change in PSA was ?26% (range: ?48% to + 12%). Limited experience with finasteride in men with prostate cancer suggests that the reduction in PSA of malignant origin appears to be no greater than the percentage reduction in PSA of benign origin. These effects on PSA have not been shown to confer any therapeutic benefit. Physicians using finasteride should be aware of its effect on PSA levels. © 1993 Wiley-Liss, Inc.     

Significance of examination of prostate-specific antigen and prostate-specific antigen density in patients with prostatic hyperplasia and prostate cancer

Authors investigated PSA concentration and preoperative prostate volume in 113 histologically proved BPH and 31 prostatic cancer patients. PSA concentration was measured with the Hybritech kit, the prostate volume by ultrasound with the help of an ellipse and calculated by computer. There was no correlation between the age of patients and volume of the prostate, whereas a correlation was proved between marker concentration and prostate volume (p<0.0001). The difference obtained by the correlation of the prostate volume and the PSA concentration ratio between the BPH and 31 tumorous patients (PSA density) was highly significant (0.143 vs. 0.699, p<0.001). The use of PSAD further improves the diagnostic value of PSA.     

High-dose intravenous estrogen therapy in advanced prostatic carcinoma. Use of serum prostate-specific antigen to monitor response

High-dose intravenous estrogen therapy was shown to be effective in relieving bone pain due to metastatic disease in 22 of 29 (75.9%) men with advanced hormone-resistant prostate cancer. This clinical response was accompanied by significant falls in serum prostate-specific antigen (PSA) levels in 13 (44.8%) patients. It is suggested that this clinical benefit is due to a direct inhibitory effect of estrogen on prostate cancer cells.     

Correlation between tissular levels of prostatic acid phosphatase and prostate-specific antigen and hormonal response of metastatic prostatic cancer

A correlation between the serum levels of testosterone and the tissular intensity of prostatic acid phosphatase (PAP) and prostate-specific antigen (PSA) in normal prostates has been demonstrated. In prostatic cancer patients, we studied the correlation between the percentage of neoplastic cells secreting PAP and PSA and the response to androgen deprivation, and found no relationship between them. Therefore it is not possible to predict the response to hormone therapy through the grade of tissular PAP or PSA.     

Experience with prostate-specific antigen in prostatic carcinoma

A total of 71 prostatic tumour patients and 45 prostatic adenoma patients were tested for prostate-specific antigen (PSA), immunological prostatic acid phosphatase (PAP) concentration as well as serum prostatic phosphatase (SPP) and enzymic serum phosphatase. It was found among untreated patients that PSA showed the highest percentage of pathologic affection in each stage. PSA, on the evidence of clearance test in the initial days of therapy and after a follow-up period of several months, gave a good picture of the course that the disease had taken.     

Changes in molecular forms of prostate-specific antigen during treatment with finasteride

OBJECTIVE: To study the influence of finasteride treatment on the molecular forms of prostate-specific antigen (PSA) in patients with benign prostatic hyperplasia (BPH). PATIENTS AND METHODS: Total PSA, free PSA and PSA complexed to alpha1-antichymotrypsin (PSA-alpha1ACT) were measured in plasma and serum from 40 men with BPH and a total PSA of < 20 ng/mL, using in-house and commercial immunoassays, before and during treatment with finasteride (30 men) or placebo (10 men). RESULTS: The baseline values were not significantly different between the groups, with mean (sd) total plasma PSA levels of 3.6 (4.3) and 4.8 (5.9) ng/mL in the finasteride and placebo groups, respectively. Finasteride, but not placebo, induced a significant reduction in total PSA, free PSA and PSA-alpha1ACT levels in plasma and serum (P < 0.001). However, complexed-to-total (c/t) and free-to-total (f/t) PSA ratios remained constant in both groups, both in plasma and serum, during the follow-up. CONCLUSION: The decrease in total PSA after finasteride treatment results from a proportional reduction in its two major molecular forms, free PSA and PSA-alpha1ACT, which explains why the c/t and f/tPSA ratios do not change significantly despite treatment. This suggests that routine analysis of molecular forms of PSA could improve the utility of the change in total PSA associated with finasteride for the early diagnosis of prostate cancer. It also suggests that any subsequent change in both ratios, particularly an increase in c/tPSA or a decrease in f/tPSA ratio, could be considered an early sign of neoplastic degeneration rather than a therapeutic consequence.     

Relationship between benign prostatic hyperplasia and lower urinary tract symptoms and correlation between prostate volume and serum prostate-specific antigen in clinical routine

OBJECTIVES: To evaluate how often benign prostatic hyperplasia (BPH) was diagnosed in men referred as a result of lower urinary tract symptoms (LUTS) and to investigate the correlation between prostate volume and serum prostate-specific antigen (s-PSA). MATERIAL AND METHODS: The study subjects comprised men (n = 119; mean age 68 years) consecutively referred to a urological clinic as a result of LUTS for whom the information in the referral forms gave no indications of malignant disease or infection. The patients were evaluated according to regional guidelines. RESULTS: BPH was estimated to be the main etiological agent in less than every second man. There was a statistically significant correlation between s-PSA and prostate size. However, among men with s-PSA < 1.5 ng/ml, one-third had a prostate volume of > 30 ml and 17% a prostate volume of > 40 ml. Among men with s-PSA > or = 1.5 ng/ml, as many as 18% had a prostate volume of < or = 30 ml and 42% a prostate volume of < or = 40 ml. Bladder and/or prostate cancer was diagnosed in 8% of men, mostly as a coincidental finding. CONCLUSIONS: BPH was considered to be the etiological factor in < 50% of men referred as a result of LUTS. The correlation between prostate volume and s-PSA was verified. However, interindividual variation in s-PSA was so large that its usefulness for making treatment decisions in men with LUTS must be questioned.     

Evaluation of prostate-specific antigen in untreated prostatic carcinoma

A study was performed on 290 men to compare the level of serum prostate-specific antigen (PSA) in controls, patients with benign prostatic hyperplasia (BPH) and patients with prostatic cancer. The upper limit of normal was 5.0 micrograms/l as determined in 110 elderly hospitalized males (mean age 62 years) without urological complaints. Of the 106 patients with BPH, 33% had raised values above 5.0 micrograms/l. Values above 10 micrograms/l were found in 18 BPH patients. A positive correlation was found between prostate volume (grams of tissue removed during transurethral resection) and preoperative PSA levels (r = 0.55, n = 106, p less than 0.001). PSA levels above 10 micrograms/l were found in 4% of BPH patients with a prostate volume of less than 20 g (n = 54), in contrast with 45% of patients with a prostate volume above 40 g (n = 20). The sensitivity of this PSA assay (cutoff level 10 micrograms/l) as established in 74 prostate carcinoma patients was 31% for category T0 (n = 13), 56% for category T1-2 (n = 16), 75% for category T3-4 (n = 20) and 100% for category M1 or N1-4 (n = 25). In an earlier study prostatic acid phosphatase (PAP) was measured in these same samples. PSA appeared to be much more sensitive than PAP. Seventeen of the 74 prostatic carcinoma patients (23%) had normal PAP levels but their PSA values were raised above 10 micrograms/l, while in only 2 patients an increased PAP level was combined with a normal PSA.(ABSTRACT TRUNCATED AT 250 WORDS)     

Relationship between prostate specific antigen density, microvessel density and prostatic volume in benign prostatic hyperplasia and advanced prostatic carcinoma

The aim of this study was to investigate the relationship between prostate specific antigen density and prostate volume with microvessel density in patients with benign prostatic hyperplasia and advanced prostatic carcinoma. Sixty-eight patients with benign prostatic hyperplasia and 11 patients with advanced prostatic carcinoma participated in the study. The paraffin blocks of all patients were stained with CD34 by the standard immunohistochemical technique and microvessel density, prostate specific antigen density and prostatic volume were determined. In patients with benign prostatic hyperplasia the mean microvessel density, mean prostate specific antigen density and mean prostatic volume were 74±89±22.73, 0.12±0.10 and 59.97±27.0 ml, respectively. There was no correlation between prostate specific antigen density and mean prostatic volume or microvessel density (r=0.079 and −0.095, respectively). In patients with advanced prostatic carcinoma the mean microvessel density, mean prostate specific antigen density and mean prostatic volume were 147.90±47.55, 0.63±0.41 and 54.00±22.42 ml, respectively. In this group, while there was a good correlation between prostate specific antigen density and microvessel density (r=0.785), no significant correlation was found between prostatic volume and microvessel density (r=−0.07). There was significant statistical difference in patients with advanced prostatic carcinoma compared to patients with benign prostatic hyperplasia in terms of mean microvessel density (p<0.0001). The findings that there was no correlation between prostatic volume and MVD either in benign prostatic hyperplasia or in prostatic carcinoma suggest that microvessel development is not correlated with prostatic volume but may be correlated with morphology.     

Production of serum-free and total prostate-specific antigen due to prostatic intraepithelial neoplasia

OBJECTIVE: High serum total prostate-specific antigen (PSA) levels have proven to be predictive of concurrent cancer but the role of prostatic intraepithelial neoplasia (PIN) in the production of total (t) and free (f) PSA is still the subject of research. In this study we wanted to discover whether variations in serum fPSA and tPSA levels are caused by PIN. MATERIAL AND METHODS: We reviewed the medical records of 87 patients: in 32 of them the diagnosis of isolated PIN was made from surgical samples (simple prostatectomy, n = 19; radical cystectomy, n = 13); in 30 patients a diagnosis of benign prostatic hyperplasia (BPH) without PIN or prostatic carcinoma was made after simple prostatectomy (n = 20) or radical cystectomy (n = 10); and in 25 patients a clinically significant prostatic cancer was diagnosed and these patients underwent radical prostatectomy. All patients underwent a standard preoperative evaluation, including serum fPSA and tPSA determinations and PSA density. RESULTS: The frequency of isolated PIN in simple prostatectomy specimens was 6.3%. The mean f/t PSA ratios were 17.66% in the 32 patients with PIN, 19.2% in the 8 patients with low-grade PIN, 17.6% in the 24 patients with high-grade PIN, 24.2% in patients with BPH and 13% in patients who underwent radical prostatectomy. CONCLUSIONS: We believe that to make a definitive diagnosis of isolated PIN without carcinoma, study of the whole prostate gland is necessary, in order to definitively exclude the presence of concurrent neoplastic foci. Our data show that PIN does not contribute to tPSA levels and density; however, it may be responsible for a slight reduction in the f/t PSA ratio, with a significant reduction in cases with high-grade PIN (17.6%) compared to those with BPH (24.2%).     

Primary prostatic carcinoid tumor with intracytoplasmic prostatic acid phosphatase and prostate-specific antigen

A case of prostatic carcinoid tumor with lymph node metastases is reported. The patient was a 78-year-old male who died in ventricular fibrillation. At autopsy, a 2 X 2 cm, white, irregular tumor was found in the prostate and there were several enlarged para-aortic lymph nodes. Both specimens contained a characteristic carcinoid tumor. Argyrophil stains revealed strong positivity in the primary as well as in the metastatic tumors. Electron micrographs prepared from formalin-fixed tissue demonstrated numerous membrane-bound dense-core granules. Immunoperoxidase-labeled antibodies against both prostatic acid phosphatase and prostate-specific antigen localized in the tumor cells. The ultrastructural and immunohistochemical results support differentiation of the tumor cells toward both prostatic epithelial cells and endocrine cells. We believe that this is the first reported case of a prostatic carcinoid tumor in which specific prostatic tissue markers have been demonstrated in the tumor cells.     

Seminal plasma prostate-specific antigen level in benign prostatic hyperplasia

INTRODUCTION: We evaluated the role of the seminal plasma PSA level in the prediction of the response to alpha-blocker treatment in patients with benign prostatic hyperplasia. MATERIALS AND METHODS: 18 male patients with lower urinary tract symptoms were enrolled in the study. After their blood was sampled for PSA, ejaculates of all the subjects were obtained. Serum and seminal plasma PSA levels were calculated by Active PSA IRMA kit. Patients were given 4 mg/day doxazosin for a period of 6 weeks, following which their International Prostate Symptom Score (IPSS) evaluation was repeated. The correlation between serum PSA, seminal plasma PSA and PSA density levels and the percentage improvement in IPSS was investigated. RESULTS: The mean serum PSA level, the mean PSA density and the mean seminal PSA level of the patients were 2.7 +/- 1.2 ng/ml, 0.05 +/- 0.02 ng/ml/cm(3) and 0.7 +/- 0.39 g/l, respectively. The percentage improvement in IPSS varied from 26.9 to 53.5%. Serum PSA and serum PSA density were not useful in the prediction of the response to alpha-blocker treatment, but the seminal PSA levels correlated with the percentage improvement in the IPSS (p = 0.017). CONCLUSIONS: Seminal plasma PSA has been found to be a better predictor of the response to alpha-blocker treatment when compared to serum PSA and PSA density.     

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.     

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.     

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.     

Contribution of bone scintigraphy, prostatic acid phosphatase and prostate-specific antigen to the monitoring of prostatic cancer

Changes in the serial measurements of serum prostatic acid phosphatase (PAP), and prostatic specific antigen (PSA) have been compared against changes in serial bone scans in 120 patients with prostatic cancer. Of 54 patients who presented with negative bone scans 10 developed skeletal metastases, the PAP and PSA levels were rising in 5 and 9 of these patients, respectively. Local progression occurred in a further 9 patients in whom PAP was rising in 8 and PSA in all 9. In the 66 patients with previously documented skeletal metastases bone scan evidence of progression was seen in 36. At the time of the first evidence of progression PAP was rising in 20 (55%) and PSA was rising in 26 (72%). In 4 patients neither marker was raised at the time of first evidence of progression. We discuss the value of 'routine' serial bone scintigraphy in monitoring patients with prostatic cancer.     

Prostate-specific antigen and prostate-specific antigen derivatives as predictors of benign prostatic hyperplasia progression

Benign prostatic hyperplasia (BPH) is the most common urologic affliction in aging men, leading to adverse clinical outcomes in a significant proportion of the population. Serum prostate-specific antigen (PSA) has been established as a marker for prostate cancer for the past two decades but more recently has been recognized as an equally important marker of BPH presence and progression. Over this time, the discovery and study of multiple isoforms of PSA have led to even more sensitive and specific methods to differentiate BPH from prostate cancer. Herein we review the expression, processing, and biochemistry of PSA and its derivatives and discuss the potential of these isoforms, both individually and in combination, to serve as determinants of BPH severity and progression.     

An algorithm for prostate cancer detection in a patient population using prostate-specific antigen and prostate-specific antigen density

Summary Prostate-specific antigen (PSA) is the most accurate serum marker for cancer of the prostate (CaP). However, its sensitivity and specificity are suboptimal, especially at values ranging between 4.1 and 10.0 ng/ml (monoclonal), because benign prostatic hypertrophy and hyperplasia (BPH) and CaP frequently coexist in this range. This study was undertaken to determine the value of incorporating prostate volume measurements with serum PSA levels in a quotient (PSA/volume) entitled PSA density (PSAD). A total of 3140 patients were analyzed and stratified by serum PSA, digital rectal examination (DRE), transrectal prostate ultrasound (TRUS), TRUS volume determination and PSAD. All patients were referred for evaluation and therefore do not represent a screened population. Patients underwent prostate biopsies when abnormalities in TRUS or DRE were detected. Although both PSA and PSAD have statistical significance when the serum PSA value is 4.0 ng/ml, neither has clinical significance in differentiating BPH from CaP. At serum levels ranging between 4.1 and 10.0 ng/ml, PSA has no ability to differentiate BPH from CaP, whereas PSAD does so with statistical and clinical significance. When the PSA value is between 10.1 and 20.0 ng/ml, only PSAD is statistically significant. When PSA exceeds 20 ng/ml, PSAD is redundant. We conclude that all patients with an abnormality on DRE or TRUS should undergo prostate biopsy. If the PSA value is 4.0 ng/ml, TRUS and PSAD are not warranted and routine biopsy is not recommended. For intermediate PSA levels, 4.1–10.0 ng/ml, TRUS, TRUS prostate volume, and PSAD are important. The use of PSAD provides unique information regarding the need for biopsy and the likelihood of CaP. At PSA levels ranging between 10.1 and 20.0 ng/ml, PSAD will identify those patients who are less likely to have CaP, but all should undergo biopsy. If the PSA value is >20 ng/ml, all patients should undergo a biopsy.     

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.