EFFECT OF EXOGENOUS TESTOSTERONE ON PROSTATE VOLUME, SERUM AND SEMEN PROSTATE SPECIFIC ANTIGEN LEVELS IN HEALTHY YOUNG MEN

Purpose

We investigate and define the effects of exogenous testosterone on the normal prostate.

Materials and Methods

A total of 31 healthy volunteers 21 to 39 years old were randomized to receive either 100, 250 or 500 mg. testosterone via intramuscular injection once a week for 15 weeks. Baseline measurements of serum testosterone, free testosterone and prostate specific antigen (PSA) were taken at week 1. Semen samples were also collected for PSA content and prostate volumes were determined by transrectal ultrasound before testosterone injection. Blood was then drawn every other week before each testosterone injection for the 15 weeks, every other week thereafter until week 28 and again at week 40. After the first 15 weeks semen samples were again collected, and prostate volumes were determined by repeat transrectal ultrasound.

Results

Free and total serum testosterone levels increased significantly in the 250 and 500 mg. dose groups. No significant change occurred in the prostate volume or serum PSA levels at any dose of exogenous testosterone. Total semen PSA levels decreased following administration of testosterone but did not reach statistical significance.

Conclusions

Despite significant elevations in serum total and free testosterone, healthy young men do not demonstrate increased serum or semen PSA levels, or increased prostate volume in response to exogenous testosterone injections.     

Effect of Digital Rectal Examination and Needle Biopsy on Serum Total and Percentage of Free Prostate Specific Antigen Levels

Purpose

We determined the effect of digital rectal examination and prostatic biopsy on serum total and free prostate specific antigen (PSA) concentrations in men undergoing screening for prostate cancer.

Materials and Methods

In 93 men recruited from our PSA screening program we measured the serum concentrations of total and free PSA on 3 occasions during a 30-day interval before performing digital rectal examination. Total and free PSA measurements were repeated 1 and 24 hours after the rectal examination. Serum total and free PSA also was measured immediately before, and 1 hour, 24 hours and 1 week after prostatic biopsy in 30 men.

Results

Biological variation for total and free PSA was 14.7 and 14.0%, respectively. At 1 hour after rectal examination total and free PSA increased by more than the biological variation in 31 and 48% of the men, respectively. Increases were significantly greater in men whose initial PSA concentrations were less than 4.0 ng./ml. There was a dramatic increase in total and percentage of free PSA in all men 1 hour after prostatic biopsy. Increases in percentage of free PSA were greater in men whose biopsies revealed cancer. Total PSA remained elevated for at least 1 week in most men, while percentage of free PSA returned to within or less than the biological variation of the baseline level in 90% of the men by 24 hours.

Conclusions

Digital rectal examination causes a modest increase in total and percentage of free PSA. Prostate needle biopsy causes more dramatic increases in both forms of PSA. Free PSA is preferentially released into the serum after prostatic manipulation and appears to be cleared more rapidly than complexed PSA. The differential return of the different PSA forms to baseline levels after biopsy could affect the use of measurements of the percentage of free PSA in clinical practice.     

The Influence of Ejaculation on Serum Levels of Prostate Specific Antigen

Purpose

While prostatic manipulation and surgery have been shown to increase serum prostate specific antigen (PSA), the influence of ejaculation on serum PSA remains controversial. We examined the effect of ejaculation on serum PSA levels.

Materials and Methods

We evaluated 100 men 25 to 35 years old with no history of surgery or inflammatory disease of the urogenital tract. Serum PSA was evaluated 1 and 24 hours after ejaculation, and serum testosterone and seminal fluid PSA levels were determined.

Results

In all men a baseline PSA level was detected. There were no statistically significant changes in serum PSA and testosterone 1 and 24 hours after ejaculation. Mean PSA concentration was significantly higher in seminal plasma than in serum. However, we did not observe a correlation between serum and seminal plasma PSA levels.

Conclusions

Based on our data ejaculation does not affect serum PSA concentration in young men, and there seems to be no physiological relationship between ejaculation and PSA level.     

Biological Variation of Total, Free and Percent Free Serum Prostate Specific Antigen Levels in Screening Volunteers

Purpose

We determined the biological variation of the total, free and percent free serum prostate specific antigen (PSA) in men 50 years old or older.

Materials and Methods

Between July 1995 and February 1996 we studied 84 healthy men from our PSA screening study to determine biological variation by calculating the coefficients of variation of 3 PSA measurements on blood samples drawn from each subject 2 weeks apart.

Results

The mean coefficients of variation for total, free and percent free serum PSA were 15, 17 and 14%, respectively. Age, total PSA and ejaculation were not confounding factors in this analysis (that is multivariate R² less than 5% for all indexes).

Conclusions

There is a mean variation of approximately 15% in measurements of total, free and percent free PSA that does not appear to be significantly affected by age and total PSA level.     

Comparison of the pre-treatment testosterone levels in benign prostatic hyperplasia and prostate cancer patients

Objectives

To compare serum testosterone and prostate specific antigen (PSA) levels of patients diagnosed of prostate cancer to those with benign prostatic hyperplasia (BPH).

INFLUENCE OF FINASTERIDE ON FREE AND TOTAL SERUM PROSTATE SPECIFIC ANTIGEN LEVELS IN MEN WITH BENIGN PROSTATIC HYPERPLASIA

Purpose

Finasteride therapy for benign prostatic hyperplasia (BPH) results in a marked lowering of serum prostate specific antigen (PSA) levels. However, little is known about the effect of finasteride on unbound or free serum levels of PSA. Such information would be important since percent free PSA may substantially improve the cancer specificity of PSA testing. Thus, we prospectively studied the effect of finasteride therapy on total and free serum PSA levels.

Materials and Methods

In a randomized, placebo controlled, double-blind trial 40 men with histologically confirmed BPH (age range 52 to 78 years) were treated with either 5 mg. finasteride daily (26 patients) for 9 months or placebo (14) for 6 months. Prostate volume was assessed by transrectal ultrasound. Serum levels of free and total PSA were measured from archived serum samples stored at −70C at baseline and for as long as 9 months of treatment.

Results

In the finasteride group mean total PSA levels declined from 3.0 ng./ml. at baseline to 1.5 ng./ml. after 6 months of treatment (50% decrease, p < 0.01). In the placebo group, with similar baseline levels, no significant change was observed. PSA density declined significantly in finasteride treated men (p <0.01) but not in men receiving placebo. The mean percent free PSA (13 to 17% at baseline) was not altered significantly by finasteride or placebo.

Conclusions

Total PSA serum levels decreased by an average of 50% during finasteride therapy but percent free PSA did not change significantly. This information is potentially useful in the interpretation of PSA data used for early detection of prostate cancer in men receiving finasteride. However, further studies are required to demonstrate the use of percent free PSA to detect the development of cancer.     

STABILITY OF FREE AND TOTAL PROSTATE SPECIFIC ANTIGEN IN SERUM FROM PATIENTS WITH PROSTATE CARCINOMA AND BENIGN HYPERPLASIA

Purpose

Instability of prostate specific antigen (PSA) in serum might complicate the interpretation of the free-to-total PSA ratio. We studied the in vitro stability of free PSA and total PSA in serum of patients with prostate cancer or benign prostate hyperplasia (BPH), and of elderly man without known prostate disease. Furthermore, we investigated conditions to stabilize the in vitro values in serum.

Materials and Methods

The effects of storage at 4C on free and total PSA were investigated in serum of 32 men with prostate cancer, 25 with BPH and 29 older than 70 years. All had total PSA less than 25 micro g./l. The influence of total PSA levels on in vitro changes in free-total PSA was studied in serum of 39 other prostate cancer patients (total PSA 1.7 to 298 micro g./l.). Stabilization studies were performed in yet another series of samples from 54 prostate cancer patients (total PSA 1.3 to 238 micro g./l.) by adjustment of serum pH to 5.5 before storage. Free and total PSA was measured by a commercial immunofluorometric assay, as well as by in-house immunofluorometric assays. Statistical analyses of the results were performed by analysis of variance with repeated measures.

Results

We found no difference between the results obtained by the 2 assay systems. After 7 days at 4C there was a slight decrease in total PSA in sera of prostate cancer patients, BPH patients and men older than 70 years. A decrease in mean free PSA values occurred in all groups (21.3, 15.7 and 14.6%, respectively). The decrease of free PSA with time was significant (p <0.0001) in all groups but there was no significant difference among the groups (p = 0.16). The concomitant decrease in free-to-total PSA ratio was significant in all groups (p <0.0001). This change was group dependent (p = 0.003), with the largest decrease in the prostate cancer group. Large interindividual differences were observed. Storage at 4C for 7 days of sera of 39 patients with localized and disseminated prostate cancer (total PSA 1.7 to 298 micro g./l.) gave a more pronounced decrease in free PSA than in total PSA. Adjustment of serum pH to 5.5 had a stabilizing effect on free PSA and on the free-to-total PSA ratio, giving a significantly smaller change in both values (p <0.0001).

Conclusions

In vitro instability of free PSA in serum and large interindividual differences should be considered when using the ratio of free-to-total PSA in evaluation of patients with suspected prostate cancer. Serum samples should be stored frozen if not analyzed immediately or acidified to pH 5.5. Interpretation of data from determination of free-to-total PSA ratio should be done with caution if the sampling and storage conditions are not known.     

Extraprostatic Production of Prostate Specific Antigen is Under Hormonal Control

Purpose

Prostate specific antigen (PSA) is the most useful tumor marker in urology. It is produced primarily by the epithelial cells of the ducts and acini of the prostate gland. Extraprostatic production of PSA is provided mainly by the periurethral glands, leading to measurable urine but undetectable serum levels of PSA in women and in men following radical prostatectomy for pathologically localized disease.

Materials and Methods

We investigated the effect of continuous testosterone substitution (250 mg. every 4 weeks) on urinary PSA excretion in 20 patients who converted from the female to male gender. We compared the results to urine levels in 20 women who did not receive testosterone.

Results

Mean urinary PSA plus or minus standard deviation was 1.73 +/− 1.68 ng./ml. in controls and 12.03 +/− 10.47 ng./ml. in converted patients, a statistically significant difference (p <0.0001). Serum PSA did not differ between groups.

Conclusions

Our data demonstrate that extraprostatic PSA production is under androgen control.     

Can Free and Total Prostate Specific Antigen and Prostatic Volume Distinguish Between Men With Negative and Positive Systematic Ultrasound Guided Prostate Biopsies?

Purpose

We evaluated the role of free and total serum prostate specific antigen (PSA) and prostate volume in discriminating between men with negative and positive transrectal ultrasound guided biopsies.

Materials and Methods

A total of 104 consecutive men with a positive biopsy and at least 3 mm. of prostate cancer was compared to 110 consecutive men with a negative biopsy. Prostate volume was determined by transrectal ultrasound. Total PSA was determined by the Tosoh AIA-600† PSA assay and free PSA was measured by the PSA II Dianon‡ assay. We determined the free-to-total PSA ratio, free and total PSA densities, and the relationship of free PSA and free-to-total PSA ratio to prostate volume.

Results

Using a 23% cutoff value of free-to-total PSA, only 22.7% of biopsies were preventable in patients with a negative biopsy but 9.6% of the cancers were missed. At a total PSA of 4 to 10 ng./ml. 44.4% of the biopsy negative cases were correctly identified while missing 9.1% of the cancers if a 20% free PSA cutoff is used. For total PSA more than 10 ng./ml. an 18% free PSA cutoff properly identified 30.2% of the biopsy negative cases while missing 9.3% of the cancers. Percent free PSA is a better discriminant than prostate volume for total PSA more than 4 ng./ml. and the combination was not helpful. Free PSA density was identical in patients with negative and positive biopsies. There was no relationship between free PSA or free-to-total PSA ratio levels and prostate volume.

Conclusions

Use of a single discriminant criterion of free-to-total PSA ratio in the practical clinical setting of distinguishing negative and positive biopsies appears useful in patients with a total PSA of 4 to 10 ng./ml. Since free PSA is unrelated to prostate volume in biopsy negative and positive cases the physiological basis of free PSA is an enigma.     

A comparison of the free fraction of serum prostate specific antigen in men with benign and cancerous prostates: the best case scenario

Purpose

In most previous studies of free-to-total serum prostate specific antigen (PSA) ratios, the specimens from patients with prostate cancer or those with benign prostatic hyperplasia (BPH) have not been highly characterized. We compared preoperative sera from post-radical prostatectomy patients with clinically significant cancers of at least 2 cm.³ to sera from those with BPH and large, biopsy negative prostates.

Materials and Methods

We used 2 different time resolved immunofluorometric assays for free and total PSA, and a combination of a chemoluminescent immunoassay for free PSA detection with an immunoradiometric assay for total PSA to measure free and total PSA. The serum ratios of free-to-total PSA in these assays were compared to those obtained previously from gel filtration studies. Sera from 51 men with prostate cancer volumes of 2 to 18 cm.³ were compared to those from 48 men with BPH and a mean prostate volume of 78 plus/minus 7 cm.³. The respective mean serum PSA levels plus or minus standard deviation were 10.0 plus/minus 6.3 and 8.9 plus/minus 7.2 ng./ml.

Results

Monoclonal assays for free PSA confirmed the previous study with gel filtration. For PSA 4 to 10 ng./ml., 94 to 95 percent of the men with prostate cancer were correctly diagnosed, with a cutoff of less than 15 percent for free-to-total PSA on immunofluorometric assay and less than 14 percent for chemoluminescent immunoassay with immunoradiometric assay. However, 46 percent (immunofluorometric assay) and 36 percent (chemoluminescent immunoassay and immunoradiometric assay) of men with BPH did not have enough free PSA for diagnosis of BPH (that is 36 to 46 percent false-positive rate).

Conclusions

For total PSA 4 to 10 ng./ml., the sensitivity of approximately 15 percent free-to-total PSA for prostate cancer is high (94 to 95 percent) but 36 to 46 percent of men with BPH and a large gland will not be correctly identified. For PSA 2 to 4 ng./ml., no ratio of percent free-to-total PSA discriminated BPH from prostate cancer.     

STABILITY OF SERUM TOTAL AND FREE PROSTATE SPECIFIC ANTIGEN UNDER VARYING STORAGE INTERVALS AND TEMPERATURES

Purpose

Measurement of total serum prostate specific antigen (PSA) is widely used as an aid to early detection of prostate cancer. Measurement of the ratio of free-to-total PSA (percentage of free PSA) may help increase specificity of PSA testing. We prospectively studied the effects of varying the storage temperature and interval on total and free PSA levels.

Materials and Methods

We measured the baseline total and free serum PSA levels in 36 volunteers (mean age 66 years) and then retested aliquots of these serum samples after varying storage intervals (24 hours, 2 weeks and 9 months) at 3 different temperatures (4C, −20C and −70C). Volunteers represented a spectrum of prostatic conditions (PSA levels 2.0 to 4.0 ng./ml., PSA levels greater than 4.0 ng./ml. without cancer and PSA levels greater than 2.0 ng./ml. with prostate cancer). We used repeated measures analysis of variance to test for changes in total and free PSA levels as a function of time and temperature. We also evaluated the impact of storage at different temperatures and times on the percentage of free PSA.

Results

Across groups total and free serum PSA decreased from the baseline level differentially as a function of longer storage interval and higher temperature (p <0.05). No significant difference was found for change in total PSA at 24 hours, 2 weeks or 9 months for storage temperatures of −20C compared with −70C. A significant change from baseline level was found for free PSA when stored in −20C compared with −70C for 2 weeks but the magnitude of the change was modest.

Conclusions

For storage intervals up to 9 months total PSA is more stable than free PSA under temperature conditions ranging from 4C to −70C. This differential stability has important implications for the clinical evaluation of percentage of free PSA to distinguish between benign and malignant diseases of the prostate.     

Combined finasteride and flutamide therapy in men with advanced prostate cancer

Objectives

To evaluate the efficacy of combined finasteride and flutamide therapy in men with advanced prostate cancer by determining (1 ) the short-term tolerability of finasteride monotherapy and its effect on serum prostate-specific antigen (PSA) and hormone (testosterone, dihydrotestosterone) levels, and (2) the effects of the addition of flutamide on tolerability and on serum PSA and hormone levels.

Methods

Thirteen hormone-naive men with advanced prostate cancer (4 with Stage D2, 1 with Stage D1, 1 with Stage DO, 7 with rising PSA levels after radical prostatectomy [n = 2]or definitive radiation therapy [n = 5]) were initially treated with 5 mg finasteride daily. Flutamide (250 mg three times a day) was added after serum PSA levels stabilized.

Results

Finasteride alone (median 5 weeks) had no significant effect on serum PSA levels (P>0.05). Combined finasteride and flutamide resulted in a mean 91% reduction in serum PSA levels, with 85% of men achieving a nadir serum PSA level of less than 4.0 ng/mL and 46% achieving undetectable levels (0.2 ng/mL or less). Finasteride alone had no significant effect on serum testosterone levels (P>0.05) but did result in a mean 74% reduction in serum dihydrotestosterone levels. Combined finasteride and flutamide resulted in a mean 56% increase in serum testosterone levels but had no additional effect on serum dihydrotestosterone levels (P>0.05). Side effects occurred in 85% (gynecomastia or breast tenderness in 62% [8 of 13]and diarrhea in 23% [3 of 13]) of men on combined therapy. Potency was preserved in 66%. Combined finasteride and flutamide therapy was withdrawn from 15% (2 of 13) because of flutamide-induced diarrhea and from 23% (3 of 13) because of disease progression. All remaining patients (8 of 13) have serum PSA levels below 4.0 ng/mL and 4 of these 8 have undetectable levels. These men have received combined finasteride and flutamide for a median 11 months (range 6 to 19).

Conclusions

Finasteride monotherapy is inadequate therapy for advanced prostate cancer, but combined finasteride and flutamide may be a reasonable alternative for men with advanced prostate cancer who refuse conventional hormone therapy.     

THE USE OF PERCENT FREE PROSTATE SPECIFIC ANTIGEN FOR STAGING CLINICALLY LOCALIZED PROSTATE CANCER

Purpose

The free-to-total serum prostate specific antigen (PSA) ratio (percent free PSA) has been demonstrated to have clinical use for early detection of men with prostate cancer with total PSA levels between 4.0 and 10.0 ng./ml. Several studies evaluating the usefulness of percent free PSA for the staging of clinically localized prostate cancer have provided conflicting results. We further investigate the usefulness of percent free PSA for staging of clinically localized prostate cancer.

Materials and Methods

In 263 men with clinically localized prostate cancer who underwent radical prostatectomy total PSA and free PSA were measured preoperatively. Pathological stages were classified as organ confined in 134 cases, capsular penetration in 92, seminal vesicle involvement in 7, involvement of the surgical margins in 20 and lymph node involvement in 10.

Results

Percent free PSA was significantly different between men with organ confined versus nonorgan confined tumors (p <0.0001) and between those with favorable versus unfavorable pathology (p <0.0001). A cutoff of 12% free PSA provided a 72% positive predictive value and 52% negative predictive value for favorable pathology. A cutoff of 15% free PSA provided a 76% and 53% positive and negative predictive value, respectively, for organ confined disease.

Conclusions

These data demonstrate that the use of percent free PSA may be of additional value for the staging of clinically localized prostate cancer. The recommendations for cutoff levels of percent free PSA for detection and staging of localized prostate cancer are preliminary and can only be given for this particular assay. A large multicenter trial, controlling for age, stage and grade distribution, as well as for a uniform pathological evaluation and comparable total and free PSA assays, is required to elucidate this issue further.     

SERUM FREE PROSTATE SPECIFIC ANTIGEN AND PROSTATE SPECIFIC ANTIGEN DENSITY MEASUREMENTS FOR PREDICTING CANCER IN MEN WITH PRIOR NEGATIVE PROSTATIC BIOPSIES

Purpose

We examined the usefulness of measurements of free prostate specific antigen (PSA) and PSA density for predicting prostate cancer in men who had had a prior negative biopsy, a serum PSA level of 4.1 to 10.0 ng./ml. and benign findings on prostate examination.

Materials and Methods

We measured percent free serum PSA and PSA density in 163 male volunteers age 50 years or older who were advised to have repeat prostatic biopsies for a serum PSA level of 4.1 to 10.0 ng./ml.

Results

Of 99 men who had repeat biopsies 20 (20%) had prostate cancer detected. Prostate cancer was significantly associated with lower free PSA level and higher PSA density, with overlap in 83% of the cases. The use of percent free PSA cutoffs of 28 and 30% would have detected 90 and 95% of cancers, respectively, and avoided 13 and 12% of the biopsies, respectively. PSA density cutoffs of 0.10 and 0.08 would have detected 90 and 95% of cancers, respectively, and avoided 31 and 12% of biopsies, respectively.

Conclusions

Free PSA and PSA density predict prostate cancer in men who have had prior negative prostatic biopsies, serum PSA levels of 4.1 to 10.0 ng./ml. and a benign prostate examination. Both parameters may be used to avoid unnecessary biopsies with an acceptable decrease in sensitivity. Further studies are needed to determine cutoffs to be used in clinical practice.     

Significance of Serum Free Prostate Specific Antigen in the Screening of Prostate Cancer

Purpose

The significance of serum free prostate specific antigen (PSA) in the screening of prostate cancer was examined.

Materials and Methods

A prospective clinical trial was conducted on 701 male volunteers 50 years old or older. Serum free PSA was determined and biopsies were performed if PSA was greater than 4 ng./ml. or if digital rectal examination was suspicious for cancer.

Results

Of the men 187 (27 percent) had a PSA of greater than 4 ng./ml. (11 percent) and/or a suspicious digital rectal examination (19 percent). Of 116 biopsies performed in the 701 men cancer was detected in 13 (1.9 percent). PSA detected more tumors (12 of 13, 92 percent) than digital rectal examination (9, 69 percent). Receiver operating characteristic analysis showed that the optimal free PSA-to-PSA ratio (free PSA ratio) was 12 percent. The positive predictive value for cancer according to PSA with free PSA ratio (50 percent, 10 cancers in 20 biopsies) was significantly greater (p = 0.0473) than that according to PSA alone (24 percent, 12 cancers in 50 biopsies), which indicated that 30 of 50 biopsies were avoided with only 2 cancers missed when PSA and free PSA were used for biopsy indication.

Conclusions

Free PSA determination might eliminate unnecessary biopsies in men with a PSA of more than 4 ng./ml. with minimal missed cancers.     

Pitfalls in Interpreting Prostate Specific Antigen Velocity

Purpose

The concept of prostate specific antigen (PSA) velocity as an improved marker for prostate cancer detection is intriguing. However, before this concept is applied to individual patients several confounding parameters must be addressed. We determined the variability of serum PSA levels in men without prostate cancer.

Materials and Methods

We reviewed data from a prostate cancer screening program, and determined inter-assay and individual variability of the serum PSA values for a 2-year followup period in 265 men clinically free of prostate cancer.

Results

Our average inter-assay coefficient of variation was 7.5 percent. Therefore, we considered only PSA changes exceeding plus/minus 15 percent as significant. Fluctuations in serum PSA occurred in 78 percent of the men during the observation period, and 12.5 percent had at least a single PSA increase exceeding 0.75 ng./ml. per year. Fluctuations were noted throughout the entire range of serum PSA levels but became progressively larger with an increasing mean PSA.

Conclusions

The inter-assay variability must be considered when interpreting PSA velocity. Individual fluctuations in serum PSA dictate an observation period of at least 2 years before PSA velocity is considered abnormal.     

RATIO OF FREE-TO-TOTAL PROSTATE SPECIFIC ANTIGEN IN SERUM CANNOT DISTINGUISH PATIENTS WITH PROSTATE CANCER FROM THOSE WITH CHRONIC INFLAMMATION OF THE PROSTATE

Purpose

We demonstrate the effect of chronic inflammation of the prostate on the ratio of free-to-total prostate specific antigen (PSA) in serum calculated as a percentage of free PSA and, therefore, that percentage of free PSA is an unspecific means to distinguish among prostate cancer, chronic prostatitis and benign prostatic hyperplasia (BPH).

Materials and Methods

Total, free and percentage of free PSA was measured in 66 men with prostate cancer, 119 with BPH and 17 with asymptomatic chronic prostatitis. In all patients the diagnosis was histopathologically confirmed by microscopic examination of prostatic specimens after sextant biopsy, transurethral prostatic resection or prostatectomy.

Results

The median values of total, free and percentage of free PSA were 4.11 micro g./l., 0.75 micro g./l. and 20.4% in patients with BPH, 10.0 micro g./l., 0.84 micro g./l. and 8.5% in those with prostate cancer, and 7.60 micro g./l., 1.23 micro g./l. and 10.6% in those with chronic prostatitis. Patients with prostate cancer and chronic prostatitis had a significantly lower percentage of free PSA than those with BPH. Receiver operating characteristics curve analysis showed that percentage of free PSA as a discriminator between prostate cancer and BPH was not suitable for differentiating between prostate cancer and chronic prostatitis.

Conclusions

Chronic prostatitis is not characterized by elevated total PSA concentrations alone but also by a decreased percentage of free PSA, a tendency similar to that in prostate cancer. This unspecific change in percentage of free PSA must be considered to interpret the percentage of free PSA correctly.     

Tamoxifen for flutamide/finasteride-induced gynecomastia

Objectives

Current therapies for advanced prostate carcinoma lead to a marked decrease in serum testosterone levels, which renders patients impotent. In preliminary studies, combination therapy with flutamide and finasteride has been used as an alternative therapy for the treatment of prostate carcinoma because potency can be preserved. Both of these agents can cause gynecomastia and breast/nipple tenderness.

Methods

Six men being treated for advanced prostate carcinoma with flutamide/finasteride combination therapy developed painful gynecomastia, which was treated with tamoxifen 10 to 30 mg/day for 1 month. Clinical follow-up included breast measurements and determination of prostate-specific antigen (PSA), testosterone, and estradiol levels.

Results

While on this combination therapy for prostate carcinoma, 4 of 6 patients experienced a decrease in PSA level to less than 0.5 ng/mL. All patients remained potent. Serum testosterone increased in each patient who had a baseline level drawn. Estradiol levels were noted to be elevated in 4 of 6 patients at the time of evaluation for gynecomastia. After treatment with tamoxifen, circulating estradiol levels increased in 3 patients from 1.3 to 2.2 times the baseline level. Five patients experienced complete resolution of breast and nipple pain on tamoxifen 10 mg/day within the first month. The other patient had to be treated with 30 mg/day for 1 additional month, which subsequently resulted in pain resolution.

Conclusions

These preliminary results suggest that low-dose tamoxifen is useful in treating painful gynecomastia for those patients on flutamide/finasteride combination therapy for advanced prostate carcinoma.     

Effect of Extracorporeal Shock Wave Lithotripsy on Prostate Specific Antigen

Purpose

We evaluated the effects of extracorporeal shock wave lithotripsy (ESWL^*) of distal ureteral calculi on serum prostate specific antigen (PSA).

Materials and Methods

A total of 29 consecutive men with distal ureteral calculi at a maximum of 25 mm. from the ureteral orifice, and without any history of urinary tract infection, benign prostatic hyperplasia or prostate cancer underwent ESWL with the Dornier MPL 9000 × lithotriptor. The therapeutic focus size was 48 × 7 mm. PSA was measured exactly 5 minutes before ESWL, as well as 120 minutes, 24 hours and 7 days after termination of treatment.

Results

Fragmentation rate was 100 percent and all patients were stone-free within 1 week of therapy. There was no statistically significant difference between PSA values before and after treatment. Only 15 patients had a slight increase in PSA at 120 minutes after treatment (range 0.01 to 0.41 ng./ml., mean 0.07).

Conclusions

ESWL can be performed in men at risk for prostate cancer without impairing the predictive value of 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.