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PubMed1996

Do prostate specific antigen and prostate specific antigen density enhance the detection of prostate carcinoma after initial diagnosis of prostatic intraepithelial neoplasia without concurrent carcinoma?

BACKGROUND: Prostatic intraepithelial neoplasia (PIN) is considered to be a precursor of prostate carcinoma in which serum levels of prostate specific antigen (PSA) have been correlated with PIN grades. The aim of this study was to determine whether PSA and prostate specific antigen density (PSAD), obtained at the time of initial diagnosis of PIN without concurrent carcinoma, can be used as predictive factors to discriminate patients with subsequent cancer on repeat biopsy. METHODS: We studied, retrospectively, the records of 93 patients with PIN (low and high grade) without concurrent carcinoma at the time of their first needle biopsy. We assessed the relationship between initial PIN grade, PSA, and PSAD with later detection of carcinoma on repeat biopsy. Patients were divided into 3 subgroups for analysis according to their initial PSA level (0-4, 4.1-10, >10 ng/mL). RESULTS: Carcinoma detection rate on repeat biopsy was 13.3% for patients with low grade PIN and 47.7% for patients with high grade PIN (P < 0.006). High grade PIN was frequently associated with subsequent carcinoma whatever the PSA level (33.3-61.9%). Low grade PIN was associated with subsequent carcinoma in 42.8% of the cases when PSA was greater than 10 ng/mL. When PSA was between 4 and 10 ng/mL, low grade PIN carcinoma was found on repeat biopsies in only 10.7% of the cases (P = 0.05). In none of the PSA subgroups did PSAD enhance later cancer detection. CONCLUSIONS: For patients with high grade PIN, the incidence of subsequent carcinoma is high, whatever the PSA values. For these cases repeat biopsies should be recommended. Patients with low grade PIN and PSA greater than 10 ng/mL should have repeat biopsies because the incidence of subsequent carcinoma is high and comparable to high grade PIN. PSAD did not provide additional information.

Biopsy, Needle↗
PubMed1997

Radiotherapy for localized prostate carcinoma. The correlation of pretreatment prostate specific antigen and nadir prostate specific antigen with outcome as assessed by systematic biopsy and serum prostate specific antigen.

BACKGROUND: The objective of this study was to correlate the failure pattern of localized prostate carcinoma after radiotherapy (RT) with pretreatment (preTx) PSA and post-RT nadir PSA, using systematic biopsies and serum PSA in the assessment of outcome. METHODS: From January 1990 to February 1994, 207 patients treated with external beam RT were followed prospectively with systematic transrectal ultrasound-guided biopsies and measurements of serum PSA levels. Three hundred forty-three biopsies were performed, with 4-7 samples taken per session. The distribution of T classification was as follows: 19 patients had T1b, 15 had T1c, 34 had T2a, 79 had T2b/c, 53 had T3, and 7 had T4. Median follow-up was 36 months (range, 12-70 months). Failures were categorized as biochemical (chemF) (PSA > 2.0 ng/mL and > 1 ng/ mL over nadir), local (LF) (positive biopsy and PSA > 2), and distant (DF). The Cox proportional hazards model was used for multivariate analysis (MVA). RESULTS: Overall, failures were seen in 68 of 207 patients: 20 LF, 24 DF, 7 LF + DF, and 17 chemF. In univariate analysis, failures correlated significantly with preTx PSA, post-RT nadir PSA, T classification, and Gleason's score (GS). The total failure rate was 12% for T1b, T1c, and T2a; 39% for T2b and T2c; and 60% for T3 and T4 (P < 0.0001). By evaluation with preTx PSA, at 36 months the total failure rate was 3% for preTx PSA < or = 5 ng/mL 16% for 5.1-10 ng/mL, 32% for 10.1-15 ng/mL, 42% for 15.1-20 ng/mL, 63% for 20.1-50 ng/mL, and 88% for > 50 ng/mL (P < 0.0001). By evaluation with post-RT nadir PSA, at 36 months the total failure rate was 4% for nadir PSA < or = 0.5 ng/ mL, 26% for 0.6-1 ng/mL, 33% for 1.1-2 ng/mL, and 92% for > 2 ng/mL (P < 0.0001). In MVA, nadir PSA (P < 0.0001) and T classification (P < 0.0005) were independent predictors for any failure. LF occurred in 13% of patients (27 of 207). For these 27 patients, the categorization of T classification was: T1b/T1c/T2a, 7%; T2b/T2c, 16%; and T3/T4, 15% (P = not significant). In MVA, only nadir PSA (P = 0.0004) predicted for LF. DF occurred in 15% of patients (31 of 207). In MVA, nadir PSA (P < 0.0001) and T classification (P < 0.0001) predicted for DF, with pretreatment PSA of borderline significance (P < 0.05). To assess preTx predictors of outcome, post-RT nadir PSA was removed from the model. PreTx PSA then became the dominant variable to predict any failure (P < 0.0001), LF (P = 0.05), chemF (P = 0.0001), and DF (P < 0.003), while T classification also predicted for any failure (P = 0.03), chemF (P = 0.05), and DF (P < 0.0001). CONCLUSIONS: Systematic prostate biopsies, performed as part of the rigorous followup of prostate carcinoma after RT, define the patterns of failure and confirm the prognostic value of preTx PSA, post-RT nadir PSA, and T classification. Prior to treatment, preTx PSA is the overwhelming independent predictor of failure, but it is surpassed by post-RT nadir PSA when this is added to the model.

Aged↗
PubMed1997

The additional value of free prostate specific antigen to the battery of age-dependent prostate-specific antigen, prostate-specific antigen density and velocity.

This study describes the value of using the fraction of free prostate-specific antigen as a further marker in the early detection of prostate cancer. This newly introduced marker is compared to the usual battery of age-dependent total prostate-specific antigen, prostate-specific antigen density (microg/l x g tissue) and prostate-specific antigen velocity (microg/l x year). Determination of total prostate-specific antigen and free prostate-specific antigen was performed on fresh serum samples obtained from 3470 symptomatic patients aged 45-80 attending the Urology Clinics, or their General Practitioners. Among them, 310 patients had total prostate-specific antigen above the age-dependent cut-off, and/or free/total prostate-specific antigen under 11%, with different prostate-specific antigen densities and velocities. Only 147 patients complied to undergo biopsy: in 72 of those patients, benign prostatic disease was histologically confirmed, while in 75 patients primary prostate cancer was histologically confirmed. Total and free prostate-specific antigen levels were determined using the third generation DPCs prostate-specific antigen assay performed on the Immulite automated immunoassay instrument. Total prostate-specific antigen age reference values were adopted from Oesterling et al. (J Am Med Ass 1993; 270:860-4); the prostate-specific antigen density was considered suspicious of prostate cancer if it was greater than 0.15 microg/l prostate-specific antigen per gram tissue (Seaman et al. Urol Clin N Am 1993; 20:653); prostate-specific antigen velocity greater than 0.75 microg/l x year (Carter et al., J Am Med Ass 1992; 267:215) was considered suspicious for prostate cancer. Of the 147 patients, 75 had prostate cancer and 72 had benign prostatic hypertrophy. The difference between prostate cancer and benign prostatic hypertrophy was significantly reflected only by free/total prostate-specific antigen and prostate-specific antigen velocity. These parameters also provided the best sensitivity and specificity. Only these parameters proved to be significant when using a backwards logistic regression model (prostate-specific antigen velocity, p = 0.007 odds ratio 2.782; free/total prostate-specific antigen %, p = 0.016 odds ratio 2.678). Combinations of various parameters became significant when including free/total prostate-specific antigen, increasing prostate cancer detection to 88%. We conclude that free/total prostate-specific antigen is the most significant among prostate-specific antigen quantities (total age-dependent prostate-specific antigen, prostate-specific antigen density and prostate-specific antigen velocity). Adding this parameter to other prostate-specific antigen parameters improves the discrimination between prostate cancer and benign prostatic hypertrophy for the population at risk.

Aged↗
PubMed2001

Comparison of the clinical validity of free prostate-specific antigen, alpha-1 antichymotrypsin-bound prostate-specific antigen and complexed prostate-specific antigen in prostate cancer diagnosis.

OBJECTIVE: To evaluate the diagnostic utility of free prostate specific antigen (fPSA), alpha-1- antichymotrypsin-bound PSA (PSA-ACT), complexed PSA (cPSA), and including their associated ratios to total PSA (tPSA) in serum for discrimination between prostate cancer (PCa) and benign prostatic hyperplasia (BPH). METHODS: A total of 166 white men (age: 65-88 years) with a tPSA between 2 and 20 microg/l were retrospectively analysed. Serum concentrations of tPSA, fPSA, PSA-ACT and cPSA were measured in 118 untreated PCa patients and 48 patients with BPH. The tPSA and cPSA concentrations were measured with the Bayer Immuno 1 system (Bayer Diagnostics, Tarrytown, USA). The Elecsys system 2010 (Roche Diagnostics, Mannheim, Germany) was used for determination of tPSA and fPSA. The PSA-ACT assay is a newly, developed prototype assay on the ES system (Roche Diagnostics, Mannheim, Germany). RESULTS: For statistical analysis only patients with tPSA between 2 and 20 microg/l were enrolled. The median concentrations of tPSA (Bayer: PCa 7.36 microg/l, BPH 4.03 microg/l; Roche: PCa 7.75, BPH 4.13), PSA-ACT (PCa 6.98, BPH 3.18) and cPSA (PCa 6.46, BPH 3.20) were significantly different. The median ratios of fPSA/tPSA (PCa 12.8 vs. BPH 22.4%), PSA-ACT/tPSA (PCa 89.8 vs. BPH 76.1%) and cPSA/tPSA (PCa 90.5 vs. BPH 81.7%) were significantly different between PCa and BPH patients. Using the areas under the curves, receiver operating characteristics analysis (tPSA: 2-20 microg/l) for discrimination between PCa and BPH showed that the ratios fPSA/tPSA (area under the curve: 0.77), PSA-ACT/tPSA (0.72) and cPSA/tPSA (0.78) were significantly different from tPSA (Bayer: 0.53; Roche: 0.55). PSA-ACT (0.64) and cPSA (0.59) alone were not significantly different from tPSA. The calculated ratios fPSA/tPSA, PSA-ACT/tPSA and cPSA/tPSA were not significantly different. CONCLUSION: The determination of PSA-ACT or cPSA and the associated ratios do not improve the diagnostic impact to discriminate between PCa and BPH compared to fPSA/tPSA ratio. The ratios PSA-ACT/tPSA or cPSA/tPSA can be considered to be alternative tools of fPSA/tPSA.

Aged↗
PubMed1996

Value of transrectal prostatic echography, prostate-specific antigen and rectal examination in the diagnosis of prostate cancer. Relationship with the result of prostatic biopsies.

UNLABELLED: We retrospectively reviewed the files of patients who had undergone a prostatic biopsy between July 1992 and December 1994. A total of 368 biopsies of 340 patients between 36 and 89 years old, could be used. The pathological examination was used to make the diagnosis of prostate cancer. The specificity and sensitivity values of the diagnostic examinations (TRUS, DRE, PSA and PSAD) were calculated. An abnormal TRUS image (hypodens or hyperdens area or irregular prostate) has the best sensitivity: 91.3%. PSA has the best specificity: 57.2%. The specificity and sensitivity of PSA can be improved by using the PSAD: a PSAD limit of 0.15 has a specificity of 66.4% and a sensitivity of 88.9%. The specificity and sensitivity values are also calculated for several combinations of tests. The combination of abnormal DRE or PSAD higher than 0.15 has a sensitivity of 96.2% and a specificity of 35.0%. CONCLUSION: the combination of abnormal DRE or high PSAD has a high sensitivity with a relatively good specificity. We advise to take biopsy if two or more of the examinations are suspect or if one of them is clearly abnormal.

Adult↗
PubMed2006

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.

Adult↗
PubMed2004

Comparison of prostate-specific antigen adjusted for transition zone volume versus prostate-specific antigen density in predicting prostate cancer by transrectal ultrasonography.

OBJECTIVE: Prostate-specific antigen is an excellent tumor marker, but it is not specific for prostate cancer. We evaluated the efficacy of prostate-specific antigen adjusted for transition zone volume calculated by transrectal ultrasonography in predicting prostate cancer in men with intermediate prostate-specific antigen levels of 4.1 to 10.0 ng/mL compared with prostate-specific antigen density. METHODS: Between June 1998 and December 2001, prostate-specific antigen adjusted for transition zone volume was obtained from 131 patients who underwent ultrasonographically guided biopsies and had prostate-specific antigen of 4.1 to 10.0 ng/mL. Prostate-specific antigen density was calculated by dividing total serum prostate-specific antigen by total prostate volume, and total serum prostate-specific antigen was divided by transition zone volume to yield prostate-specific antigen adjusted for transition zone volume. This was compared with prostate-specific antigen density via receiver operating characteristic curves. RESULTS: Of 131 patients, 34 (26%) had prostate cancer, and 97 (74%) had benign prostatic hyperplasia on pathologic examination. Total prostate volume was correlated with transition zone volume (P < .001). Mean prostate-specific antigen adjusted for transition zone volume and prostate-specific antigen density were 0.71 +/- 0.25 and 0.27 +/- 0.09 ng x mL(-1) x mL(-1) in patients with prostate cancer and 0.32 +/- 0.09 and 0.16 +/- 0.05 ng x ml(-1) x mL(-1) in patients with benign prostatic hyperplasia. With a cutoff value of 0.35 ng mL(-1) x mL(-1), prostate-specific antigen adjusted for transition zone volume had sensitivity of 82% and specificity of 84%. Receiver operating characteristic curve analysis showed that prostate-specific antigen adjusted for transition zone volume predicted biopsy outcome significantly better than prostate-specific antigen density (P < .05). CONCLUSIONS: Prostate-specific antigen adjusted for transition zone volume is more accurate than prostate-specific antigen density in distinguishing prostate cancer from benign prostatic hyperplasia in men with intermediate serum prostate-specific antigen of 4.1 to 10.0 ng/mL. Determination of transition zone volume by transrectal ultrasonography may be helpful for predicting the probability of positive biopsy results.

Biopsy↗
PubMed2007

Age adjusted prostate specific antigen and prostate specific antigen velocity cut points in prostate cancer screening.

PURPOSE: We identified age adjusted prostate specific antigen and prostate specific antigen velocity cut points for prostate cancer biopsy. MATERIALS AND METHODS: A cohort of 33,643 men was retrieved from the Duke Prostate Center database. Of this group 11,861 men with 2 or more prostate specific antigen values within 2 years were analyzed for age adjusted prostate specific antigen and prostate specific antigen velocity performance in cancer risk assessment using a receiver operating characteristic curve. RESULTS: In the 11,861 men prostate cancer prevalence was 273 (8.0%), 659 (14.9%) and 722 (17.9%) in the groups of men 50 to 59 years old, 60 to 69 and 70 years old or older. In prostate cancer groups median prostate specific antigen and prostate specific antigen velocity in men 50 to 59 vs 70 years old or older were 5.6 vs 8.1 ng/ml and 1.37 vs 1.89 ng/ml per year (<0.0001). In men 50 to 59 years old the sensitivity and specificity were 82.1% and 80.7% at prostate specific antigen 2.5 ng/ml, and 84.3% and 72.4% at prostate specific antigen velocity 0.40 ng/ml per year, higher than those in men 70 years old or older at prostate specific antigen 4.0 ng/ml or prostate specific antigen velocity 0.75 ng/ml per year. Decreasing the prostate specific antigen cut point to 2.0 ng/ml and the prostate specific antigen velocity cut point to 0.40 ng/ml per year in men 50 to 59 years old improved the cancer detection rate but decreased the positive predictive value. CONCLUSIONS: Current biopsy guidelines (prostate specific antigen 4.0 ng/ml or greater, or prostate specific antigen velocity 0.75 ng/ml or greater per year) underestimated cancer risk in men 50 to 59 years old. Prostate specific antigen and prostate specific antigen velocity cut points should be age adjusted. In men 50 to 59 years old prostate specific antigen and prostate specific antigen velocity cut points could be decreased to 2.0 ng/ml and 0.40 ng/ml per year, respectively. Factors of age, sensitivity, specificity, positive predictive value and cancer prevalence are critical for obtaining the desired balance between cancer detection and negative biopsy.

Age Factors↗
PubMed2006

Prostate tissue and leukocyte levels of n-3 polyunsaturated fatty acids in men with benign prostate hyperplasia or prostate cancer.

OBJECTIVE: To compare the levels of n-3 polyunsaturated fatty acids (PUFAs) in leukocytes and prostate tissue in men with prostate cancer or benign prostatic hyperplasia (BPH), as dietary intake of n-3 PUFAs has been linked to the risk of prostate cancer; the prostate-specific antigen (PSA) level was also compared to prostate tissue levels of n-3 PUFAs. PATIENTS AND METHODS: Prostate tissue was obtained and leukocytes isolated from 20 men with prostate cancer and 35 with BPH. The n-3 PUFAs alpha-linolenic acid (ALA), eicosapentanoic acid (EPA) and docosahexaenoic acid (DHA) were measured in prostate tissue and in peripheral blood leukocytes using gas chromatography. PSA levels were measured in all of the men. RESULTS: There was a strong positive correlation between EPA and DHA in leukocytes and in prostate tissue (EPA: r = 0.80, DHA: r = 0.53, both P < 0.001) in all the men, whereas there was no association between the content of ALA in leukocytes and in prostate tissue (r = -0.15). Men with BPH had similar levels of ALA in leukocytes and in prostate tissue, but men with prostate cancer had more ALA in prostate tissue than in leukocytes. The PSA level was significantly positively correlated with ALA level in prostate tissue (r = 0.42, P < 0.01) but there was no significant correlation between PSA level and EPA and DHA levels. There were no significant correlations between PSA level and n-3 PUFA levels in leukocytes. CONCLUSION: Dietary intake of the marine n-3 PUFAs reflected in EPA and DHA levels in leukocytes are also reflected in EPA and DHA levels in prostate tissue in men with and without prostate cancer. However, there is a discrepancy between the levels of ALA in leukocytes and in prostate tissue, with higher levels in men with prostate cancer. This is in accordance with the strong positive association between PSA and ALA levels in prostate tissue. This study therefore does not support the hypothesis that intake of marine n-3 PUFAs might protect against prostate cancer, but lends support to the deleterious role of ALA in the development of prostate cancer.

Aged↗
PubMed1998

Prostate cancer and prostate bed SPECT imaging with ProstaScint: semiquantitative correlation with prostatic biopsy results.

BACKGROUND: ProstaScint (Cytogen Corporation, Princeton, NJ) murine monoclonal antibody imaging is FDA-approved for imaging of prostate cancer patients at high risk for metastatic disease and patients postprostatectomy with a rising serum prostate-specific antigen (PSA) level. ProstaScint is a murine monoclonal antibody which targets prostate-specific membrane antigen (PSMA). PSMA expression is upregulated in primary and metastatic prostate cancer. FDA Cytogen (Princeton, NJ) protocol studies using 111indium-labeled ProstaScint revealed correlation between areas of increased concentration in the prostate and biopsy-proven tumors in patients imaged pretherapy. METHODS: In our study, four transverse, single-photon emission tomography (SPECT) images were isolated and regions of interest were selected and correlated with pretherapy prostate biopsy results. Prostate cancer and normal tissue prostate/muscle background (P/M) ratios were derived, so that postprostatectomy/radiation therapy patients could be evaluated for the presence of residual prostate cancer. Twenty-three pretherapy prostate cancer patients with quadrant/sextant biopsies had SPECT 96-hr 111indium ProstaScint pelvic images. The four transverse 1-cm slices above the midline penile blood pool were chosen, and four to six 27-30-pixel regions of interest were placed over the prostate bed. The background muscle region of interest was placed over the external obturator muscle region. The P/M ratio was calculated and compared to the quadrant/sextant prostatic biopsy result. The same procedure was applied to 17 posttherapy prostate cancer patients with rising PSA. RESULTS: In the 23 pretherapy prostate cancer patients, there was a correlation between the P/M ratio of at least 3.0 in 32 of 35 prostatic cancer biopsy regions, and there was correlation with P/M ratios less than 3.0 in 82 of 89 negative biopsy regions. Seventeen posttherapy patients underwent ProstaScint studies. Six underwent biopsy, with typically one biopsy site per patient. All 6 had P/M ratios greater than 3.0 in the biopsied region. Five out of six biopsies revealed residual prostate cancer. CONCLUSIONS: A prostate/muscle ratio was developed from 111indium ProstaScint regions of interest obtained on 1-cm SPECT transverse slices through the prostate bed in 23 patients preprostatic cancer therapy. A P/M ratio above 3.0 correlated in the majority of positive cases, and a P/M ratio below 3.0 was demonstrated in negative prostatic biopsy cases. The P/M ratio of above 3.0 or below 3.0 also separated those posttherapy prostate cancer patients with rising PSA who had residual prostate carcinoma in the prostate bed.

Aged↗
PubMed2002

Accumulation of [11C]acetate in normal prostate and benign prostatic hyperplasia: comparison with prostate cancer.

Carbon-11 acetate positron emission tomography (PET) has been reported to be of clinical value for the diagnosis of prostate cancer. However, no detailed analysis has yet been carried out on the physiological accumulation of [(11)C]acetate in the prostate. The purpose of this study was to elucidate the physiological accumulation of [(11)C]acetate in the prostate using dynamic PET. The study included 30 subjects without prostate cancer [21 with normal prostate and nine with benign prostatic hyperplasia (BPH)] and six patients with prostate cancer. A dynamic PET study was performed for 20 min after intravenous administration of 555 MBq of [(11)C]acetate. The standardised uptake value (SUV) at 16-20 min post tracer administration and the early-to-late-activity ratio of the SUV (E/L ratio), which was determined by dividing the SUV(6-10 min) by the SUV(16-20min), were calculated to evaluate the accumulation of [(11)C]acetate. The prostate was clearly visualised and distinguished from adjacent organs in PET images in most of the cases. The SUV of the prostate (2.6+/-0.8) was significantly higher than that of the rectum (1.7+/-0.4) or bone marrow (1.3+/-0.3) ( P<0.0001 in each case). The SUV of the normal prostate of subjects aged <50 years (3.4+/-0.7) was significantly higher than both the SUV for the normal prostate of subjects aged > or =50 years (2.3+/-0.7) and that of subjects with BPH (2.1+/-0.6) ( P<0.01 in each case). The primary prostate cancer in six cases was visualised by [(11)C]acetate PET. However, the difference in the SUV between subjects aged > or =50 with normal prostate or with BPH and the patients with prostate cancer (1.9+/-0.6) was not statistically significant. There was also no significant difference in the E/L ratio between subjects aged > or =50 with normal prostate (0.98+/-0.04) or BPH (0.96+/-0.08) and patients with prostate cancer (1.02+/-0.12). In conclusion, a normal prostate exhibits age-related physiological accumulation of [(11)C]acetate. Careful interpretation of [(11)C]acetate PET images of prostate cancer is necessary because the SUV and the E/L ratio for the normal prostate and for BPH overlap significantly with those for prostate cancer.

Acetates↗
PubMed1999

Serum prostate-specific antigen as a predictor of prostate volume in men with benign prostatic hyperplasia.

OBJECTIVES: To assess the utility of prostate-specific antigen (PSA) as a predictor of prostate volume by characterizing the relationship between prostate volume and serum PSA in men with symptomatic benign prostatic hyperplasia (BPH) and no evidence of prostate cancer, stratified by decade of life. METHODS: Placebo-controlled multicenter trials in patients with BPH and a safety study in normal young men provided baseline measurements of serum PSA and prostate volume. The analyses included patients with a baseline prostate volume measured by either transrectal ultrasound (TRUS) or magnetic resonance imaging and baseline serum PSA. A common central laboratory was used for all but one of the individual studies; both laboratories used the Hybritech method. Patients 80 years of age or older were excluded. Patients with a baseline serum PSA greater than 10 ng/mL were excluded to reduce the likelihood of including occult prostate cancer cases. The patients in the BPH trials were screened at baseline by digital rectal examination (DRE) and serum PSA. Those with suspicious findings underwent TRUS-guided biopsy; only patients with negative biopsies are included in these analyses. RESULTS: The analyses included 4627 patients, 4448 from the BPH trials and 179 from the safety study. The men in the BPH trials were older (mean age+SE, 63.7+0.10 years) than the men in the safety study (mean age + SE, 30.8+/-0.43), had larger prostates (mean volume+/-SE, 43.7+/-0.38 mL versus 26.3+/-0.49 mL in the safety study), and had higher serum PSA values (mean+/-SE, 2.6+/-0.03 ng/mL versus 0.7+/-0.39 ng/mL in the safety study). The relationship between prostate volume and serum PSA was evaluated using only the BPH trial data. Prostate volume and serum PSA have an age-dependent log-linear relationship (ie, their logarithms are linearly related, and the parameters of the relationship depend on age). Older men tend to have a steeper rate of increase in prostate volume with increasing serum PSA (P < 0.00 for differences between slopes), and there was a slight tendency for PSA density to increase with age. Receiver operating characteristic (ROC) curves were constructed to evaluate the ability of serum PSA to predict threshold prostate sizes in men with BPH. The ROC curve analyses revealed that PSA had good predictive value for assessing prostate volume, with areas under the curve ranging from 0.76 to 0.78 for various prostate volume cutoff points (30, 40, and 50 mL). Conclusions. Prostate volume is strongly related to serum PSA in men with BPH and no evidence of prostate cancer, and the relationship depends on age. Since treatment outcome or risk of long-term complications depend on baseline prostate volume, serum PSA can estimate the degree of prostate enlargement sufficiently accurately to be useful for therapeutic decision making. To achieve a specificity of 70% while maintaining a sensitivity between 65% and 70%, approximate age-specific criteria for detecting men with prostate glands exceeding 40 mL are PSA > 1.6 ng/mL, >2.0 ng/mL, and >2.3 ng/mL for men with BPH in their 50s, 60s, and 70s, respectively.

Adult↗
PubMed1994

The use of prostate specific antigen density to improve the sensitivity of prostate specific antigen in detecting prostate carcinoma.

BACKGROUND: Prostate specific antigen (PSA) is useful as a tumor marker for monitoring patients with prostate cancer after definitive therapy. Limitations have been noted when PSA was used for the early detection of prostate cancer. The use of prostate specific antigen density [PSAD = PSA (ng/ml)/prostate volume (cc)] has been suggested to differentiate benign from malignant prostate disease. METHODS: A retrospective analysis of 559 men who underwent transrectal prostate ultrasound and biopsy for an abnormal PSA value (> 4.0 ng/ml) and/or an abnormal prostate gland by digital rectal examination (DRE) was performed. Prostate specific antigen density evaluation was performed on all men, and its utility for diagnosing prostate cancer was compared with those of PSA and DRE. RESULTS: Two hundred, sixty seven (47%) of the 559 men had positive biopsies for prostate cancer. Sixty-one men had PSA levels of less than 4.0 ng/ml, and 17 (27.8%) of these men had positive biopsies for prostate cancer. No patient with a normal DRE had a positive biopsy regardless of the prostate specific antigen density (PSAD) value. PSAD was not more useful than PSA alone in detecting prostate cancer in this group. Two hundred, seventy-seven men had PSA values between 4.1 and 10.0 ng/ml, and 110 (40.0%) had positive biopsies for prostate cancer. For this group as a whole, the mean PSA values of the positive and negative biopsy groups showed no significant difference. The mean PSAD was significantly different (P < 0.0001) between the positive and negative biopsy groups. Two hundred, twenty-one men had PSA values of greater than 10.0 ng/ml, and 140 (63%) had positive biopsies for prostate cancer. Prostate specific antigen density was no more useful than PSA alone in distinguishing men with positive or negative biopsies for prostate cancer in the entire group. In the subset of patients with a normal DRE, (including no benign prostatic hyperplasia) the mean PSAD appeared useful (P < 0.004) in distinguishing the positive from the negative biopsy groups, whereas the mean PSA was not. CONCLUSION: These results suggest that PSAD is useful in discriminating prostate cancer in men with normal DRE and PSA levels between 4.1 and 10.0 ng/ml.

Biomarkers, Tumor↗
PubMed1987

Prostatic specific antigen and prostatic acid phosphatase in the monitoring and staging of patients with prostatic cancer.

Serum prostatic specific antigen and prostatic acid phosphatase levels were measured retrospectively and evaluated in 357 men with benign prostatic hypertrophy and in 209 men with various stages of prostatic carcinoma. Although prostatic specific antigen values were elevated in 21 per cent of the patients with benign prostatic hypertrophy, the elevations usually were low and did not interfere with clinical interpretation. Prostatic specific antigen was elevated in 98 per cent of 86 men with active stage D2 disease; in 22 per cent of the men prostatic specific antigen was the only elevated marker. In contrast, prostatic acid phosphatase was the only elevated marker in 1 per cent of the patients with stage D2 disease and neither marker was elevated in 2 per cent. Among 74 patients in whom prostatic specific antigen and prostatic acid phosphatase determinations were made before radical prostatectomy, prostatic specific antigen was elevated substantially (greater than 10 ng. per ml.) in 59 per cent (26 of 44) with extracapsular disease and in only 7 per cent (2 of 30) without extracapsular disease. More importantly, of those 28 patients with substantially elevated prostatic specific antigen levels 26 (93 per cent) had extracapsular disease. Serial serum measurements showed that prostatic specific antigen either reflected or predicted clinical status in more than 97 per cent of the patients. We conclude that prostatic specific antigen is an excellent serum tumor marker for monitoring patients with prostatic carcinoma and that it surpasses prostatic acid phosphatase in this regard. Prostatic specific antigen also may be useful in staging prostatic carcinoma and it may change our attitudes significantly about the therapeutic responses to this cancer.

Acid Phosphatase↗
PubMed2005

Do prostatic infarction, prostatic inflammation and prostate morphology play a role in acute urinary retention?

OBJECTIVE: To investigate whether there is a role of prostatic infarction, prostatic inflammation and prostate morphology in acute urinary retention (AUR) etiology. METHODS: Ninety-eight consecutive male patients who were admitted to our clinic with either AUR or lower urinary tract symptoms (LUTS) were involved in the study. Patient age ranged from 43 to 88 years (median age 70). Group 1 consisted of 53 (54%) patients with AUR, and Group 2 consisted of 45 (46%) patients with LUTS. In Group 1 and Group 2, 58.4% (n:31) and 62.2% (n:28) of the patients underwent transurethral prostate resection, 41.6% (n:22) and 37.8% (n:17) of the patients underwent suprapubic transvesical prostatectomy, respectively. Each patient was asked about the factors: smoking habits, taking previous general anesthesia and preexisting cardiovascular disease such as hypertention and atherosclerotic coronary vascular disease which may lead to AUR via prostatic infarct. Prostatic infarction, prostatic inflammation and prostatic morphology were examined in the patients' specimen. RESULTS: Mean age, median serum prostate-specific antigen (PSA) level, and prostatic inflammation ratio were significantly higher in Group 1. There were not significant differences between the groups regarding prostate volume, prostatic infarction ratio and a type of prostatic morphology. In the present study, except for taking previous general anesthesia and preexisting cardiovascular disease, only prostatic inflammation was found important contributory factor on AUR. AUR risk was 3.03 times higher in the patients with prostatic inflammation (95%CI 1.28-7.15) (p = 0.01). CONCLUSIONS: No significant effect of prostatic infarction was found on occurrence of AUR which was more frequent in elderly patients. Prostatic inflammation may have an important risk factor in AUR etiology. Additionally, serum PSA levels were higher in AUR group. No association was found between a type of prostatic morphology and AUR.

Adult↗
PubMed1998

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 microg./l., 0.75 microg./l. and 20.4% in patients with BPH, 10.0 microg./l., 0.84 microg./l. and 8.5% in those with prostate cancer, and 7.60 microg./l., 1.23 microg./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.

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PubMed2005

Prostate cancer in a large prostate is associated with a decreased prostate specific antigen failure rate after brachytherapy.

PURPOSE: A large prostate has been found to correlate with improved prostate cancer survival in men undergoing radical prostatectomy. In the current study we analyzed the relationship of prostate size and prostate specific antigen (PSA) failure in men undergoing brachytherapy for localized prostate cancer. MATERIALS AND METHODS: We studied data on 613 men who had undergone I radioactive seed implantation. Average patient age +/- SD was 65 +/- 7.2 years. Average prostate volume ultrasonically measured at seed insertion was 40 +/- 15 ml. All patients had a minimum of 2 years of followup. RESULTS: Men with a large prostate had increased freedom from failure compared to men with a small prostate. Failure time in men with an intermediate size prostate was between that for large and small prostates. This difference in failure rates was significant (log rank test p = 0.0002). We further analyzed our data with Cox regression. Large prostate size significantly correlated with increased time to PSA failure (p = 0.013) and it was independent of the significant effects of Gleason score, PSA, disease stage (p <0.001), minimal radiation dose covering 90% of prostate volume (p = 0.008) and hormone treatment, including androgen ablation (p = 0.001). CONCLUSIONS: Some investigators have postulated that paracrine signals acting to regulate epithelial proliferation in benign prostatic hypertrophy have beneficial influences on coexistent prostate cancer. Our finding that the effect of prostate size is independent of Gleason score, PSA and disease stage supports the paracrine signal mechanism. If a circulating substance, such as a cytokine, might be responsible for improved survival, this substance might be useful for treating prostate cancer. Moreover, since we found that prostate size is independent of PSA, Gleason score and tumor stage for predicting outcome, we hypothesize that patients with a small prostate treated with brachytherapy might benefit from hormone treatment and larger radiation doses. These measures are now generally reserved for men with more advanced tumors, higher PSA and increased Gleason scores.

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PubMed1993

Measurement of prostate specific antigen and gamma-seminoprotein ratio: a new means of distinguishing benign prostatic hyperplasia and prostate cancer.

We measured a ratio of serum prostate specific antigen (PSA) and gamma-seminoprotein concentrations (referred to as the PSA/gamma-seminoprotein ratio) and evaluated its usefulness for the diagnosis of prostate cancer. Between April 1988 and October 1992, 214 men underwent prostatic biopsy and/or transurethral resection of the prostate, and the disease was diagnosed pathologically. Of 214 patients 127 were diagnosed as having benign prostatic hyperplasia, prostatitis or a normal prostate (no cancer), while 87 had prostate cancer. Of 61 patients with a serum PSA level greater than 10 ng./ml. 50 (82.0%) had prostate cancer, compared to 31 of 84 (36.9%) with a serum PSA level of 3.0 to 10 ng./ml. Of 113 patients with a serum gamma-seminoprotein level greater than 4.0 ng./ml. 52 (46.0%) had prostate cancer. The mean plus or minus standard deviation of the PSA/gamma-seminoprotein ratio for 127 patients without cancer was 0.942 +/- 0.564, while that for 87 prostate cancer patients was 12.840 +/- 45.327 (Wilcoxon p < 0.0001). The mean plus or minus standard deviation of the PSA/gamma-seminoprotein ratios for 37 prostate cancer patients with a PSA level of 10 ng./ml. or less and for 50 prostate cancer patients with a PSA level of more than 10 ng./ml. were 2.044 +/- 0.767 and 20.829 +/- 58.757, respectively. Even the mean PSA/gamma-seminoprotein ratio for prostate cancer patients with a PSA level of 10 ng./ml. or less was significantly greater than that for patients without cancer (Wilcoxon p < 0.0001). The sensitivities for PSA (cutoff value 3.0 ng./ml.), gamma-seminoprotein (cutoff value 4.0 ng./ml.) and PSA/gamma-seminoprotein ratio (cutoff value 1.45) were 93.1%, 59.8% and 92.0%, respectively, and the specificities were 49.6%, 52.0% and 91.3%, respectively. Of 91 patients with a PSA/gamma-seminoprotein ratio of 1.45 or more 80 (87.9%) had prostate cancer, while 116 of 123 (94.3%) with a PSA/gamma-seminoprotein ratio of less than 1.45, had no cancer. These results suggest that PSA/gamma-seminoprotein ratio yields the same sensitivity as PSA and more specificity than PSA levels, offering significant advantage over PSA in detecting prostate cancer. The mean plus or minus standard deviations of PSA/gamma-seminoprotein ratios for stages A, B, C and D prostate cancer were 1.847 +/- 0.786 (11 patients), 2.740 +/- 1.536 (30), 7.626 +/- 9.140 (12) and 27.149 +/- 70.500 (34), respectively.(ABSTRACT TRUNCATED AT 400 WORDS)

Antigens, Neoplasm↗