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Citrate as an in vivo marker to discriminate prostate cancer from benign prostatic hyperplasia and normal prostate peripheral zone: detection via localized proton spectroscopy.

OBJECTIVES: This study was designed to determine whether citrate levels detected by localized 1H spectroscopy could reliably discriminate regions of prostate adenocarcinoma from surrounding regions of normal peripheral zone and benign prostatic hyperplasia (BPH). METHODS: In 28 patients and 5 volunteers stimulated echo proton spectroscopy was used in conjunction with endorectal surface coils to obtain water-suppressed 1H spectra from regions of normal prostate peripheral zone, BPH, and prostate cancer. 1H spectra from prostate cancer patients were correlated with pathologic areas identified on T2-weighted endorectal coil magnetic resonance (MR) images and histologic study of the step-sectioned gland after surgery. RESULTS: The major finding of in vivo studies was consistently lower citrate levels in prostate cancer compared with BPH and normal prostate peripheral zone. This was reflected by significantly (P < 0.05) lower mean citrate/(creatine plus choline) peak area ratio observed for regions of cancer (0.67 +/- 0.17) compared with BPH (1.21 +/- 0.29) and normal peripheral zone (1.46 +/- 0.28). Moreover, there was no overlap of individual cancer and normal peripheral zone citrate ratios and no significant difference between citrate ratios in regions of normal peripheral zone in young volunteers (1.28 +/- 0.14) and age-matched patients (1.46 +/- 0.28). The observed alterations in vivo citrate levels were supported by citrate concentration data obtained from extracts of histologically proven samples of normal, benign, and malignant prostatic tissues removed at surgery. In vitro citrate levels in the normal peripheral zone (30.9 +/- 8.5 mumol/g wet weight) and BPH (46.3 +/- 5.4 mumol/g wet weight) were significantly higher than those for prostate cancer (3.74 +/- 0.54 mumol/g wet weight). CONCLUSIONS: These studies further demonstrate the potential of citrate as an in vivo marker for discriminating prostate cancer from surrounding regions of normal peripheral zone and BPH.

Adenocarcinoma↗

A lectin histochemistry comparative study in human normal prostate, benign prostatic hyperplasia, and prostatic carcinoma.

The partial oligosaccharide sequences of glycoconjugates and the nature of their glycosidic linkages were investigated in normal human prostate, benign prostatic hyperplasia (BPH) and prostatic carcinoma by means of lectin histochemistry, using light microscopy and Western blot analysis. The labeling pattern of BPH differed from that of normal prostate in having more intense staining with DSA, HPA, UEA-I and AAA, and in showing lesser staining with WGA and SBA. Prostatic carcinoma differed from normal prostates in displaying the more intense labeling with PNA, DSA, SBA, DBA, UEA-I and AAA, and in having lesser labeling with WGA. The main differences in labeling pattern between prostatic carcinoma and BPH were that the latter specimens showed more marked staining with PNA, DSA, DBA, SBA, UEA-I and AAA, and lesser staining with WGA and HPA. The staining patterns of SNA, MAA, ConA, LCA and GNA were similar in all three groups of specimens. For most of the lectins studied, including those showing a similar immunohistochemical staining in the three groups of specimens studied, the Western blot analysis showed differences in the banding pattern among normal, hyperplastic, and carcinomatous prostates. Present results suggest that the glycosylation of proteins was modified in both BPH and prostatic carcinoma. In BPH a strong expression of N-acetylgalactosamine residues occurred, while in prostatic carcinoma an increase of sialic acid, galactose and fucose residues was observed. No changes in mannose residues were detected.

Adult↗

The clinical utility of measuring free-to-total prostate-specific antigen (PSA) ratio and PSA density in differentiating between benign prostatic hyperplasia and prostate cancer.

OBJECTIVE: To evaluate the role of free-to-total prostate-specific antigen ratio (f/tPSA), prostate volume and PSA density in differentiating between men with prostate cancer and benign prostatic hyperplasia (BPH). PATIENTS AND METHODS: The study comprised 51 patients who were assessed after transurethral electroresection of the prostate (16 with prostate cancer and 35 with BPH). Patients with a tPSA of < or = 4.0 ng/mL and > or = 30.0 ng/mL were excluded from the analysis. Total and fPSA were measured using an immunoradiometric assay and prostate volume was determined by transrectal ultrasonography. The incidence of prostate cancer and BPH was then compared with the PSA variables to determine specificity and predictive value. RESULTS: Most patients with BPH had a tPSA of 4.0-6.0 ng/mL; no patients with BPH had a tPSA of > 20.0 ng/mL. Most patients with prostate cancer had a f/tPSA of 6-10%. The area under the receiver operating characteristic curve for f/tPSA was significantly greater than that for tPSA (P < 0.003). CONCLUSIONS: The measurement of f/tPSA and PSA density increase the specificity of the differential diagnosis between BPH and prostate cancer.

Aged↗

The correlation between clinical outcome and residual prostatic weight ratio after transurethral resection of the prostate for benign prostatic hyperplasia.

OBJECTIVE: To assess in a prospective study the use of a new variable, the residual prostatic weight ratio (RPWR), for evaluating the clinical outcome after transurethral resection of the prostate (TURP). PATIENTS AND METHODS: From April 1996 to June 1997, 40 men (mean age 70.4 years, range 53-85) with symptomatic benign prostatic hyperplasia were evaluated using the American Urological Association (AUA) symptom score, measurements of the mean and maximum urinary flow rate (Qave and Qmax), and by transrectal ultrasonography (TRUS) before and 16 weeks after TURP. The estimated total prostate weight was derived as 0.52 x length x width x height x the specific gravity of the prostate (1.010). The RPWR was calculated as the prostate weight after TURP divided by the initial weight, where the value after TURP was the initial weight minus that of the TURP specimen. The clinical outcome was evaluated by the difference (Delta) in AUA score, Qmax and Qave before and 16 weeks after surgery. RESULTS: There was a close correlation between the estimated prostate weight and the actual weight of the TURP specimen (r = 0.82 and 0.80 for the adenoma and total prostate, respectively). The mean (SD) RPWR, DeltaAUA score, DeltaQmax and DeltaQave were 50.1 (17.1)%, 11.5 (5. 3), 9.0 (4.2) mL/s and 6.2 (2.9) mL/s, respectively. There was a negative correlation between the RPWR and the DeltaAUA, DeltaQmax and DeltaQave (r = -0.81, -0.68, and -0.70, respectively, P < 0.05). The prostate volume estimated by TRUS decreased significantly 16 weeks after TURP. CONCLUSIONS: TRUS is a useful tool for estimating prostate weight before surgery. The smaller the RPWR at 16 weeks after TURP, the better the clinical outcome.

Aged↗

Carbohydrate structure and differential binding of prostate specific antigen to Maackia amurensis lectin between prostate cancer and benign prostate hypertrophy.

Serum prostate-specific antigen (PSA) assay is widely used for detection of prostate cancer. Because PSA is also synthesized from normal prostate, false positive diagnosis cannot be avoided by the conventional serum PSA test. To apply the cancer-associated carbohydrate alteration to the improvement of PSA assay, we first elucidated the structures of PSA purified from human seminal fluid. The predominant core structure of N-glycans of seminal fluid PSA was a complex type biantennary oligosaccharide and was consistent with the structure reported previously. However, we found the sialic acid alpha2-3 galactose linkage as an additional terminal carbohydrate structure on seminal fluid PSA. We then analyzed the carbohydrate moiety of serum PSA from the patients with prostate cancer and benign prostate hypertrophy using lectin affinity chromatography. Lectin binding was assessed by lectin affinity column chromatography followed by determining the amount of total and free PSA. Concanavalin A, Lens culinaris, Aleuria aurantia, Sambucus nigra, and Maackia amurensis lectins were tested for their binding to the carbohydrates on PSA. Among the lectins examined, the M. amurensis agglutinin-bound fraction of free serum PSA is increased in prostate cancer patients compared to benign prostate hypertrophy patients. The binding of PSA to M. amurensis agglutinin, which recognizes alpha2,3-linked sialic acid, was also confirmed by surface plasmon resonance analysis. These results suggest that the differential binding of free serum PSA to M. amurensis agglutinin lectin between prostate cancer and benign prostate hypertrophy could be a potential measure for diagnosis of prostate cancer.

Carbohydrates↗

Relationship between prostate specific antigen, prostate volume and age in the benign prostate.

The relationship between prostate specific antigen (PSA) levels, prostate volume and age was examined in 472 men who underwent PSA assay (Hybritech), digital rectal examination (DRE) and transrectal ultrasound (TRUS) as part of a community survey of benign prostatic hyperplasia following exclusion of men with prostate cancer. The mean age of the study population was 60 years (range 40-79). The mean PSA was 2.4 ng/ml and 85% of the men had levels < 4 ng/ml. There was a modest correlation between PSA and both age and prostate volume. The mean prostate and adenoma volumes were 32 ml (SD 13.4) and 15 ml (SD 10.7) respectively. Prostate volume increased with age. Linear regression analysis revealed an independent association between PSA and age when controlling for volume. The mean ratio of PSA per unit of prostate volume was 0.072 ng/ml. This ratio also increased with age. Age and prostate volume influences PSA levels independently. The sensitivity and specificity of PSA adjusted for volume and age in the diagnosis of prostate cancer need to be evaluated in association with DRE and TRUS.

Adult↗

Advantage of systematic random ultrasound-guided biopsies, measurement of serum prostate-specific antigen level and determination of prostate volume in the early diagnosis of prostate cancer.

Two hundred and sixteen patients, presenting with a suspicious digital examination (stage T3 excluded) or a level of prostate-specific antigen (PSA) greater than or equal to 2.5 ng/ml, assessed by radioimmunoassay, underwent a transrectal ultrasound examination. Prostate volume was systematically calculated and correlated to PSA level. Biopsies were performed: (1) on suspicious peripheral hypoechoic areas; ultrasound-guided biopsies; (2) systematically on the 2 prostate lobes, whatever the result of transrectal ultrasound imaging:random systematic ultrasound-guided biopsies. In the 186 patients who had never undergone prostate surgery, ultrasound-guided biopsies showed 42 prostate cancers and random systematic ultrasound-guided biopsies showed 75; 14 of the 76 patients with normal digital rectal examination and transrectal ultrasound imaging had a prostate cancer. In the 30 patients who had previously undergone surgery for benign prostatic hypertrophy, random systematic ultrasound-guided biopsies showed 18 prostate cancers, 13% more than ultrasound-guided biopsies; 75% of patients with a serum PSA greater than 5 ng/ml had a prostate cancer. A very significant correlation was found between PSA level and prostatic volume (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Antigens, Neoplasm↗

Expression of prostate specific membrane antigen (PSMA) in prostatic adenocarcinoma and prostatic intraepithelial neoplasia.

The prostatic membrane antigen (PSMA) is a protein that is expressed in the prostatic epithelium. We studied the expression of PSMA in a series of 55 patients with different stages of prostate cancer and we compared the PSMA staining in prostate cancer cells, in high-grade prostatic intraepithelial neoplasia (PIN) and in histologically benign prostatic epithelium for the same specimen. For this purpose archival paraffin-embedded specimens were studied by immunohistochemistry with a monoclonal antibody 7E11-C5.3 against PSMA using the streptavidin-biotin method. The mean percentage of PSMA immunoreactivity was 56.67% in prostate cancer (CaP) cells, and 48.6% in PIN cells, which was significantly higher than benign-appearing prostatic epithelium (5.72%) (for each pair, p<0.001). PSMA expression was greater in CaP with a higher Gleason score (p=0.01), but no relationship was found with serum PSA value. We conclude that PSMA overexpression is detected in high-grade PIN and is associated with a higher Gleason score of prostate cancer. It is a potential marker for studying carcinogenesis and progression of prostate cancer.

Adenocarcinoma↗

The combination of human glandular kallikrein and free prostate-specific antigen (PSA) enhances discrimination between prostate cancer and benign prostatic hyperplasia in patients with moderately increased total PSA.

BACKGROUND: Prostate-specific antigen (PSA) is the most reliable tumor marker available and is widely used for the diagnosis and management of prostate cancer. Unfortunately, PSA cannot distinguish efficiently between benign and malignant disease of the prostate, especially within the range of 4-10 microg/L. Among the refinements developed to enhance PSA specificity is the free/total PSA ratio, which is useful in discriminating between the two diseases within the diagnostic "gray zone". Recent data indicate that human glandular kallikrein (hK2), a protein with high homology to PSA, may be an additional serum marker for the diagnosis and monitoring of prostate cancer. METHODS: We analyzed 206 serum samples (all before treatment was initiated) from men with histologically confirmed benign prostatic hyperplasia (n = 100) or prostatic carcinoma (n = 106) with total PSA in the range of 2.5-10 microg/L. Total and free PSA and hK2 were measured with noncompetitive immunological procedures. Statistical analysis was performed to investigate the potential utility of the various markers or their combinations in discriminating between benign prostatic hyperplasia and prostatic carcinoma. RESULTS: hK2 concentrations were not statistically different between the two groups of patients. There was a strong positive correlation between hK2 and free PSA in the whole patient population. hK2/free PSA ratio (area under the curve = 0.69) was stronger predictor of prostate cancer than the free/total PSA ratio (area under the curve = 0.64). At 95% specificity, the hK2/free PSA ratio identified 30% of patients with total PSA between 2.5-10 microg/L who had cancer. At 95% specificity, the hK2/free PSA ratio identified 25% of patients with total PSA between 2.5 and 4.5 microg/L who had cancer. CONCLUSIONS: Our data suggest that hK2 in combination with free and total PSA can enhance the biochemical detection of prostate cancer in patients with moderately increased total PSA concentrations. More specifically, the hK2/free PSA ratio appears to be valuable in identifying a subset of patients with total PSA between 2.5 and 4.5 microg/L who have high probability of cancer and who should be considered for biopsy.

Aged↗

Prostate-specific membrane antigen levels in sera from healthy men and patients with benign prostate hyperplasia or prostate cancer.

Prostate-specific membrane antigen (PSMA) serum levels have been proposed to be of prognostic significance in patients with advanced prostate disease. The objective of the present study was to confirm PSMA serum expression by Western blot techniques, to determine whether such data could assist in the differentiation of benign from malignant prostatic disease, and to determine the suitability of serum PSMA measurements in predicting recurrent or progressive prostate malignancies. We measured PSMA, a transmembrane glycoprotein identified in prostate epithelial cells, in the sera of 236 normal individuals and cancer patients by Western blot analysis. Within the normal male population, PSMA levels increase with age and were found to be significantly elevated in subjects more than 50 years of age when compared to those of younger men. We did not confirm previous reports that serum PSMA measurements could distinguish late-stage prostate carcinoma from early-stage prostate carcinoma, nor did we find PSMA to be more effective than prostate-specific antigen in monitoring prostate cancer patient prognosis. Furthermore, we found elevated serum PSMA in healthy females, and, similar to the healthy male population, the levels increased with age, with the highest levels found in the sera from breast cancer patients. These latter observations further support that PSMA is not a specific biomarker for prostate cancer and that a variety of normal and diseased tissue may contribute to the serum levels of PSMA.

Adult↗

A prospective study to evaluate the role of complexed prostate specific antigen and free/total prostate specific antigen ratio for the diagnosis of prostate cancer.

PURPOSE: Patients are increasingly undergoing prostatic biopsy to identify localized prostate cancer. The decision to perform a biopsy is often made on the basis of total prostate specific antigen (PSA). However, this value lacks adequate specificity for this task. We evaluate the role that a number of these tests, including the Bayer complexed PSA (Bayer Diagnostics, Tarrytown, New York) and free/total PSA ratio, may have in our clinical practice. MATERIALS AND METHODS: A total of 160 consecutive patients attending a prostate assessment clinic were enrolled during an 18-month period in our study. All patients had a previously recorded total PSA (range 2.6 to 20.0 ng./ml.). Before transrectal ultrasound biopsy of the prostate gland, a blood sample was taken with patient consent. The findings on ultrasound were then recorded, including prostate volume. Serum samples were immediately sent for subsequent storage and analysis. RESULTS: Of the patients enrolled 109 had benign histology while 51 had prostatic carcinoma. The 2 patient groups were well matched for age. In our series patients with prostate cancer had significantly smaller prostates and higher mean total PSA. At a high sensitivity, such as 95%, it appeared that Bayer complexed PSA performed better than the other tests and ratios, with an estimated specificity of 24.8% compared with 17.4% for Bayer total PSA and 15.6% for Abbott free/total PSA (Abbott Laboratories, Abbott Park, Illinois). Receiver operator characteristics curves were drawn, and when the areas under them were calculated, we demonstrated that the area under the curve for Bayer complexed PSA (0.706) was between the values for total PSA (0.671) and free/total PSA ratio (0.731). However, the only statistically significant improvement in performance was in Bayer complexed PSA over the total PSA assays. CONCLUSIONS: Our study revealed that the overall diagnostic performance of Bayer complexed PSA appears to be better than the other PSA tests and ratios studied. The use of Bayer complexed PSA may lead to a reduction in the number of men undergoing unnecessary prostatic biopsy.

Aged↗

Expression of P-cadherin identifies prostate-specific-antigen-negative cells in epithelial tissues of male sexual accessory organs and in prostatic carcinomas. Implications for prostate cancer biology.

Cadherins constitute a family of calcium-dependent cell-cell adhesion molecules the individual members of which are essential for the sorting of cells into tissues during development. In this study, we examined the expression of E-cadherin, N-cadherin, and P-cadherin in tissues obtained from radical prostatectomies. Epithelial cells of prostatic glands, ejaculatory ducts, and seminal vesicles expressed E-cadherin but not N-cadherin. P-cadherin was expressed in epithelial cells of the seminal vesicles and ejaculatory ducts. In the prostate it was limited to the basal cells of prostatic acini, glands with basal cell hyperplasia, and atrophic glands denuded of the luminal cells. All P-cadherin-positive cells were negative for prostatic-specific antigen. Prostatic cancers were mostly P-cadherin negative, but some tumors had P-cadherin-positive areas frequently located close to ejaculatory ducts and negative for prostatic-specific antigen. The mutually exclusive expression of P-cadherin and prostatic-specific antigen suggests that these proteins are involved in differential mechanisms of cell regulation in prostate cancer. P-cadherin may become a useful marker in the diagnosis and management of patients with prostate cancer and low levels of prostatic-specific antigen.

Animals↗

Variation in the definition of biochemical recurrence in patients treated for localized prostate cancer: the American Urological Association Prostate Guidelines for Localized Prostate Cancer Update Panel report and recommendations for a standard in the reporting of surgical outcomes.

PURPOSE: The American Urological Association Prostate Guideline Update Panel was charged with updating the Guidelines for Clinically Localized Prostate Cancer. In assessing outcomes with treatment, it became apparent that a highly variable number of definitions exist with respect to biochemical recurrence. Herein, we review the variability in published definitions of biochemical recurrence and make recommendations directed toward improving this terminology by recommending a standard definition in patients treated with radical prostatectomy. MATERIALS AND METHODS: Four PubMed literature searches were performed between May 2001 and April, 2004 and covered articles published from 1991 through early 2004. The search terms included the MeSH major headings of prostate cancer and prostatic neoplasm. All potentially relevant articles were retrieved and a more detailed screen for relevance was performed. An article was considered relevant if it reported treatment outcomes of patients with clinical T1 or T2N0M0 prostate cancer. Data extractors recorded the definition of biochemical recurrence and definitions were then collapsed into categories representing the same criteria. The results of biochemical failure were subcategorized by initial treatment. RESULTS: Of 13,800 citations, a total of 436 articles were selected. Among these, a total of 145 articles contained 53 different definitions of biochemical recurrence for those treated with radical prostatectomy. Of these, the most common definition (35) was a prostate specific antigen of >0.2 ng/mL or a slight variation thereof. In addition, a total of 208 articles reported 99 different definitions of biochemical failure among those treated with radiation therapy. Of these, the American Society for Therapeutic Radiology and Oncology definition (70) and/or a variation thereof was the most commonly reported. In total, 166 different definitions of biochemical failure were identified. Following radical prostatectomy, the Panel recommends defining biochemical recurrence as an initial serum prostate specific antigen of > or =0.2 ng/mL, with a second confirmatory level of prostate specific antigen of >0.2 ng/mL. The Panel recommends the use of the American Society for Therapeutic Radiology and Oncology criteria for patients treated with radiation therapy and acknowledges that these criteria will soon be updated although not yet published. CONCLUSIONS: A high degree of variability in the definition of biochemical recurrence exists following treatment for localized prostate cancer. Strict definitions for biochemical recurrence are necessary to identify men at risk for disease progression and to allow meaningful comparisons among patients treated similarly. The Panel acknowledges the American Society for Therapeutic Radiology and Oncology criteria and future modifications thereof for those receiving radiation therapy and recommends the newly developed American Urological Association criteria for those treated with radical prostatectomy. The purpose for the establishment of this standard is for data reporting purposes and for comparison of similarly treated patients. It is not intended to represent a threshold value for which to initiate treatment. The Panel acknowledges that the clinical decision to initiate treatment will be dependent on multiple factors including patient and physician interaction rather than a specific prostate specific antigen threshold value.

Humans↗

Bone marrow prostatic specific antigen and prostatic acid phosphatase levels: are they helpful in staging prostatic cancer?

We analyzed serum and bone marrow levels of prostatic specific antigen and prostatic acid phosphatase quantified by double antibody radioimmunoassay in 70 patients. Of the patients 36 had prostatic cancer, including 23 with metastatic disease. There was a significant correlation between the serum and bone marrow levels of prostatic specific antigen and prostatic acid phosphatase independently of the metastases (p less than 0.001). No patient with prostatic cancer and positive bone marrow prostatic specific antigen or prostatic acid phosphatase levels had normal serum levels. Quantification of bone marrow prostatic specific antigen and prostatic acid phosphatase does not provide more information than does serum determination.

Acid Phosphatase↗

Evaluation of prostate specific acid phosphatase and prostate specific antigen in identification of prostatic cancer.

The peroxidase-anti-peroxidase technique was used to stain for prostate specific acid phosphatase and prostate specific antigen in 12 patients with primary tumors and in 12 patients with metastases in whom the nature of the tumor was in doubt after routine histopathological studies. Nine of the primary tumors were positive for both markers and an additional 2 tumors stained for prostate specific antigen only. Six metastatic lesions stained for both markers and a seventh for prostate specific antigen alone. Thus, 11 of 12 primary tumors and 7 of 12 metastases studied were proved to be of prostatic orgin. While the peroxidase staining was sometimes weak and uneven this method, using prostate specific antigen and prostate specific acid phosphatase, allowed for ready identification of metastases. The heterogeneity of the tumors in regard to these 2 prostate markers is demonstrated, and the value of staining for prostate specific acid phosphatase and prostate specific antigen is emphasized.

Acid Phosphatase↗

Absence of serum prostate-specific antigen and loss of tissue immunoreactive prostatic markers in advanced prostatic adenocarcinoma after hormonal therapy: a report of two cases.

We report two cases of advanced prostatic adenocarcinoma (PA) showing complete loss of three tissue immunoreactive prostatic markers, ie, prostate-specific antigen (PSA), prostatic acid phosphatase (PAP), and Leu-7 (CD57), with absence of elevated serum PSA level, despite tumor progression after hormonal therapy with or without radiotherapy. The pretreatment serum PAP in the first case and serum PAP and PSA in the second case were elevated. In both cases, the prostatic adenocarcinoma in the initial transurethral resection specimens showed positive immunoreactivity with three prostatic markers. After treatment, in both cases, the serum PSA were undetectable, and tumor cell immunostaining for three prostatic markers was negative. In addition, the posttreatment tumors in both cases showed increased number of tumor cells with neuroendocrine differentiation in comparison those in the pretreatment tumors. Although early PA without elevated serum level of PSA is common, advanced PA with absence of elevated serum PSA, associated with presence of tissue immunoreactive prostatic markers are rare. This is the first report of advanced prostatic adenocarcinomas showing loss of tumor cell prostate-specific markers with absence of elevated serum PSA level after hormonal therapy despite tumor progression.

Adenocarcinoma↗

Prospective use of free prostate-specific antigen to avoid repeat prostate biopsies in men with elevated total prostate-specific antigen.

OBJECTIVES: We prospectively evaluated whether free PSA improves the specificity of PSA and can be useful as a clinical guide to avoid repeat prostate biopsies in patients with persistent PSA elevations, normal digital rectal examinations, and previous negative prostate biopsies. METHODS: Sixty-seven men with persistent PSA elevations (median 9.5, range 4.1-24.8 ng/mL), normal digital rectal examinations and two or more prior sextant biopsies (mean 2.8) had serum collected for measurement of total and free PSA. All patients were rebiopsied to determine the receiver operating characteristics of total PSA versus percent free PSA for prostate cancer detection. RESULTS: The study biopsy identified 11 prostate cancer cases. The median percent free PSA was significantly higher at 18.0% among men without prostate cancer compared to 6.7% in men with prostate cancer (P < 0.00005). When sensitivity was plotted against 1-specificity, the area under the receiver operating characteristic curve for percent free PSA was 0.93, compared to 0.69 for free PSA density, 0.66 for PSA density, and 0.51 for PSA. In patients with elevated total PSA levels, normal digital rectal examinations and two prior negative sets of sextant prostate biopsies, a cutoff of 10% free PSA would maintain sensitivity at 91% with a corresponding specificity of 86%. CONCLUSIONS: Selective measurement of percent free PSA can significantly improve the specificity of prostate cancer screening with PSA. A low percent free PSA (< 10%) appears to be a powerful predictor of prostate cancer even after two negative prostate biopsies.

Biopsy↗

Clinical utility of the percentage of positive prostate biopsies in predicting prostate cancer-specific and overall survival after radiotherapy for patients with localized prostate cancer.

PURPOSE: To determine whether the percentage of positive prostate biopsies provides clinically relevant information to a previously established risk stratification system with respect to the end points of prostate cancer-specific survival (PCSS) and overall survival after radiotherapy for patients with clinically localized prostate cancer. METHODS AND MATERIALS: A Cox regression multivariable analysis was used to evaluate the ability of the percentage of positive prostate biopsies to predict PCSS and overall survival for 381 men who underwent radiotherapy for localized prostate cancer during the prostate-specific antigen era. RESULTS: At a median follow-up of 4.3 years (range 0.8-13.3), the presence of < or =50% positive biopsies vs. >50% positive biopsies provided a clinically relevant stratification of the 7-year estimates of PCSS (100% vs. 57%, p = 0.004) in intermediate-risk patients. Moreover, all patients could be stratified into a minimal or high-risk cohort on the basis of the 10-year estimates of PCSS (100% vs. 55%, p <0.0001) and overall survival (87% vs. 40%, p = 0.02) by incorporating the percentage of positive prostate biopsy information into a previously established risk stratification system. CONCLUSION: The clinically relevant stratification of PCSS using the percentage of positive prostate biopsies in intermediate-risk patients confirms previous findings based on prostate-specific antigen outcome. These data provide evidence to support the ability to stratify newly diagnosed patients with clinically localized disease into a minimal-risk (low-risk + low biopsy volume [< or =50%] intermediate-risk) or high-risk (high biopsy volume [>50%] intermediate-risk + high-risk) cohort for prostate cancer-specific death after conventional dose radiotherapy. Additional follow-up and independent validation are needed to confirm these findings.

Aged↗