Prostate Specific Antigen Research

Relationship Between Prostate-specific Antigen, Age, and Body Mass Index in a Prostate Cancer Screening Population

2011-11-15T10:00:00.001-06:00

Background: Recent studies questioning the benefit of prostate-specific antigen (PSA) screening have increased the need for evaluating factors contributing to variance in levels and their clinical relevance. An inverse relationship between body mass index (BMI) and PSA has been illustrated, however the clinical implications have not been specified. We performed a retrospective review of patients screened through our free screening clinic to delineate any relationship between PSA and BMI in an attempt to understand its possible clinical significance.

Methods: The authors retrospectively reviewed data collected in relation to PSA values and patient characteristics from a community outreach program supplying information and screening for prostate cancer between June of 2003 and August of 2009.

Results: Mean BMI of our patient population was 28.7 m/kg2 (SD 5.4) and our mean PSA value was 1.28 (SD 1.77). Our data indicate a small, but statistically significant decrease in PSA for an increasing BMI with a 0.026 decrease in PSA for every unit increase in BMI.

Conclusions: Our study confirms the previously reported inverse relationship between PSA value and BMI. The significance of this finding and its impact on the value do not seem to indicate a rationale to change the accepted abnormal value in obese patients and should be used in the context of the clinical scenario and other PSA altering factors.

Pater, Luke E. MD; Hart, Kimberly W. MA; Blonigen, Brian J. MD; Lindsell, Christopher J. PhD; Barrett, William L. MD
American Journal of Clinical Oncology

Seasonal variation in prostate-specific antigen levels: a large cross-sectional study of men in the UK

2011-04-03T18:31:00.001-05:00

School of Social and Community Medicine, University of Bristol, Bristol, Oncology Centre, Addenbrooke's Hospital, Cambridge, andNuffield Department of Surgery, University of Oxford, John Radcliffe Hospital, Oxford, UK.

Abstract
Study Type - Aetiology (cohort) Level of Evidence 2b What's known on the subject? and What does the study add? Evidence for seasonal or climatic effects on PSA levels is mixed and inconclusive. In this large, long-term study, no seasonal or climatic patterns in PSA levels were identified.

OBJECTIVE: To assess whether a seasonal change in prostate specific antigen (PSA) levels can be detected in men recruited to a large clinical trial.

PATIENTS AND METHODS: A total of 66 969 men aged 50-69 years were drawn from a large study conducted at general practices across the UK between 2002 and 2007. Trigonometric algorithms and regression methods were used to assess the relationship between the time of year and serum PSA and blood pressure measurements. We obtained local daily mean temperatures and hours of sunlight per day to assess whether these factors were potential mechanisms for seasonal variation in PSA levels or blood pressure. The proportion of participants who would be considered clinically at risk according to their PSA or blood pressure measurement, by month, was also assessed. The strength of associations between time of year and blood pressure were used to reinforce conclusions from the PSA models.

RESULTS: There was no relationship between time of year and PSA levels (P= 0.11) or between climate and PSA levels (P= 0.42). No difference was found in the prevalence of clinically raised PSA content by month (P= 0.50). This lack of an association with PSA content was despite our data being sufficient to provide clear evidence of an association between blood pressure and time of year (systolic P < 0.001; diastolic P < 0.001), and to show that this association was largely explained by climatic factors (temperature and sunlight).

CONCLUSIONS: There was no pattern in PSA levels by time of year, air temperature or levels of sunlight in this cohort, so there is no need to take these factors into account when reviewing PSA results

Risk Profiles and Treatment Patterns Among Men Diagnosed as Having Prostate Cancer and a Prostate-Specific Antigen Level Below 4.0 ng/mL

2010-09-15T15:53:00.000-05:00

Background Despite controversy over the benefit of prostate-specific antigen (PSA) screening, little is known about risk profiles and treatment patterns in men diagnosed as having prostate cancer who have a PSA value less than or equal to 4.0 ng/mL.

Methods We used data from the Surveillance, Epidemiology, and End Results system to describe patient characteristics and treatment patterns in the cases of 123 934 men with newly diagnosed prostate cancer from 2004 to 2006. Age-standardized treatment rates were calculated in 5-year age strata. Logistic regression was used to quantify the odds ratios (ORs) of men with low- and high-risk disease and the use of radical prostatectomy (RP) or radiation therapy (RT).

Results Men with a PSA level of 4.0 ng/mL or lower represent 14% of incident prostate cancer cases. Fifty-four percent of men diagnosed as having prostate cancer and PSA levels lower than 4.0 ng/mL harbor low-risk disease (stage, T2a, PSA level, 10 ng/mL, and Gleason score, 6), but over 75% of them received RP or RT. Men with screen-detected prostate cancer and PSA values lower than 4 ng/mL were 1.49 (95% confidence interval [CI], 1.38-1.62) and 1.39 (95% CI, 1.30-1.49) times more likely to receive RP and RT, respectively, and were less likely to have high-grade disease than men who had non–screen-detected prostate cancer (OR, 0.67; 95% CI, 0.60-0.76).

Conclusions Most men diagnosed as having prostate cancer with a PSA threshold below 4.0 ng/mL had low-risk disease but underwent aggressive local therapy. Lowering the biopsy threshold but retaining our inability to distinguish indolent from aggressive cancers might increase the risk of overdiagnosis and overtreatment.

Yu-Hsuan Shao, PhD; Peter C. Albertsen, MD; Calpurnyia B. Roberts, PhD; Yong Lin, PhD; Amit R. Mehta, MD; Mark N. Stein, MD; Robert S. DiPaola, MD; Grace L. Lu-Yao, PhD

Arch Intern Med. 2010;170(14):1256-1261. doi:10.1001/archinternmed.2010.221

Symptoms and Risk Factors for Prostate Cancer

2010-02-10T17:07:00.000-06:00

SYMPTOMS

Different people have different symptoms for prostate cancer. Some men do not have symptoms at all.

Some symptoms of prostate cancer are—

•Difficulty starting urination.
•Weak, or interrupted flow of urine.
•Frequent urination, especially at night.
•Difficulty emptying the bladder completely.
•Pain or burning during urination.
•Blood in the urine or semen.
•Pain in the back, hips, or pelvis that doesn't go away.
•Painful ejaculation.
If you have any symptoms that worry you, be sure to see your doctor right away. Keep in mind that these symptoms may be caused by conditions other than prostate cancer.

RISK FACTORS
Research has found risk factors that increase your chances of getting prostate cancer. These risk factors include—

•Age: The older a man is, the greater his risk for getting prostate cancer.1
•Family history: Certain genes (the functional and physical units of heredity passed from parent to offspring) that you inherited from your parents may affect your prostate cancer risk. Currently, no single gene is sure to raise or lower your risk of getting prostate cancer. However, a man with a father, brother, or son who has had prostate cancer is two to three times more likely to develop the disease himself.1
•Race: Prostate cancer is more common in some racial and ethnic groups than in others, but medical experts do not know why.
Researchers are trying to determine the causes of prostate cancer and whether it can be prevented. They do not yet agree on the factors that can influence a man's risk of developing the disease, either positively or negatively. Some of the factors under study include—1 2 3 4

•Vitamins, minerals, and herbal supplements.
•Diets high in animal fat, especially polyunsaturated fat.
•Men's hormone levels.
•Environmental agents (pesticide residues on foods, and industrial and occupational exposures).
References
1Bostwick DG, Burke HB, Djakiew D, Euling S, Ho SM, Landolph J, Morrison H, Sonawane B, Shifflett T, Waters DJ, Timms B. Human prostate cancer risk factors. Cancer 2004;101(10 Suppl):2371–2490.

2Vainio H, Bianchini F, eds. IARC Handbooks of Cancer Prevention, Vol 6: Weight Control and Physical Activity. Lyon, France: IARC Press; 2002.

3Curry S, Byers T, Hewitt M, eds. Fulfilling the Potential of Cancer Prevention and Early Detection.

4Platz EA, Giovannucci E. Prostate Cancer. In: Schottenfeld D, Fraumeni JF, eds. Cancer Epidemiology and Prevention, 3rd ed. New York, NY: Oxford University Press, 2006.

Prostate-specific antigen: An evolving role in diagnosis, monitoring, and treatment evaluation in prostate cancer.

2010-01-28T13:20:00.001-06:00

Prostate specific antigen (PSA) was introduced as a prostate cancer screening tool more than 20 years ago. However, there is continuing debate regarding its utility in screening for prostate cancer. Mass screening is costly, may result in the diagnosis and treatment of prostate cancers that never become clinically significant, and the evidence of a subsequent reduction in mortality is inconclusive. In addition to its role in screening, PSA is also used to monitor the progression of the disease, both localized and metastatic.

Although the evidence is contradictory, PSA is still an important tool for monitoring patient progression following treatment of definitive localized prostate cancer. However, its use in monitoring castrate-resistant prostate cancer (CRPC) is more controversial, particularly in the context of novel targeted treatments, which may have little impact on PSA levels. These issues highlight the urgent need to identify prostate cancer biomarkers that will improve early disease detection, increase accuracy of diagnosis, determine the aggressiveness of disease, and monitor treatment efficacy, particularly in late-stage disease.

This review discusses the key issues associated with the use of PSA as an early screening tool for prostate cancer, as a prognostic marker to measure disease progression in both early- and late-stage prostate cancer, and as a surrogate endpoint in clinical trials with new agents. Copyright © 2009 Elsevier Inc. All rights reserved.

Payne H, Cornford P.

Department of Oncology, UCLH NHS Foundation Trust, London, United Kingdom.

Serum Prostate-Specific Antigen Hemodilution Among Obese Men Undergoing Screening in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Tria

2009-11-24T12:36:00.000-06:00

(Cancer Epidemiol Biomarkers Prev 2009;18(3):748–51)

Background: Previous studies have shown an inverse relationship between prostate-specific antigen (PSA) concentration and body mass index (BMI). It has been recently proposed that this relationship may be explained by the larger plasma volume of obese men diluting a fixed amount of PSA (hemodilution effect). We examined this hypothesis in a cohort of men enrolled in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial.

Methods: Of 38,349 men ages 55 to 74 years randomized in PLCO to receive annual PSA and digital rectal examination screening, 28,380 had a baseline PSA, complete demographic information, and no prostate cancer diagnosis within 6 years from baseline. Self-reported height and weight were used to calculate BMI and to estimate plasma volume. PSA mass was estimated as PSA concentration times plasma volume. Multivariable linear regression models were used to investigate the relationship between PSA concentration, plasma volume, PSA mass, and BMI.

Results: PSA concentration significantly decreased with increasing BMI (P < 0.001); mean PSA values were 1.27, 1.25, 1.18, and 1.07 ng/mL among normal (BMI, 18.5-25), overweight (BMI, 25-30), obese (BMI, 30-35), and morbidly obese (BMI, >35) men, respectively. However, plasma volume also increased with increasing BMI and PSA mass showed no association with BMI, with mean values of 3.78, 3.95, 3.97, and 3.82 μg across the four BMI categories (P = 0.10).

Conclusions: This study confirms earlier findings that the inverse relationship between PSA concentration and BMI may be explained by a hemodilution effect. These findings could have implications for prostate cancer screening in large men.

PSA Doubling Time as a Predictive Factor on Repeat Biopsy for Detection of Prostate Cancer

2009-08-20T14:08:00.001-05:00

imbo M, Tomioka S, Sasaki M, Shima T, Suzuki N, Murakami S, Nakatsu H, Shimazaki J.
1Department of Urology, Asahi General Hospital, Asahi.

OBJECTIVE: Detection of prostate cancer needs a biopsy of the prostate. Suspecting cancer from an increase in Prostate Specific Antigen (PSA) has a high negative rate at an initial prostate biopsy. Cases with negative initial biopsy may be the candidates of subsequent biopsy. For lowering unnecessary repeat biopsy, the use of predictive factors before a repeat biopsy is applied for indication.

METHODS: Seventy-seven cases with negative initial prostate biopsy received a repeat biopsy and factors for the detection of cancer were examined.

RESULTS: Prostate Specific Antigen doubling time distinguished a part of cancer cases. Its sensitivity of 30, 50 and 70 months was 36.6%, 30.4% and 10%, respectively. Cancer case did not show PSA doubling time of >100 months in general. Values of PSA transition zone density, %Free/total PSA and PSA velocity were similar between cancer and no cancer cases.

CONCLUSIONS: Prostate Specific Antigen doubling time was one of the predictive factors for the detection of prostate cancer and was valuable for avoiding unnecessary repeat biopsy in some cases.

Prostate-specific antigen in vaginal fluid after exposure to known amounts of semen and after condom use: comparison of self-collected and nurse-colle

2009-07-06T16:02:00.003-05:00

BACKGROUND: Prostate-specific antigen (PSA) in vaginal fluid indicates exposure to semen , and was used to assess condom effectiveness, although validity and reliability have not been fully evaluated. Our objective was to compare PSA in self-collected samples with samples collected by a nurse.

METHODS: We conducted two studies, each with 100 women aged 18-48 years. In the first, a nurse exposed each participant to her partner's semen (10, 100 and 1000 microl), and nurse and participant collected samples. In the second, each participant sampled before and after using two male condoms (MC) and two female condoms (FC); a nurse collected another sample afterwards.

RESULTS: PSA concentration increased with semen exposure, but was lower in nurse-collected samples. Both procedures were sensitive, almost 100% after exposure to 100-1000 microl of semen . PSA detection rates with MC and FC were 13% and 28% in self-collected samples, 8% and 9% in nurse-collected samples. Concordance between sample types was 93% with the MC (95% CI: 89%; 96%), 78% with the FC (95% CI: 72%; 84%). PSA decay between sampling times may explain higher values in self-collected samples.

CONCLUSIONS: PSA is a highly sensitive surrogate endpoint for condom effectiveness studies. Self-collected and nurse-collected samples are equivalent, but sample collection timing is critical

Bahamondes L, Diaz J, Marchi NM, Castro S, Villarroel M, Macaluso M.
Department of Obstetrics and Gynaecology, Faculty of Medical Sciences, University of Campinas (UNICAMP), Campinas, SP, Brazil.

Painkillers May Prevent Prostate Problems

2009-06-25T16:19:00.001-05:00

By: Sylvia Booth Hubbard

Over-the-counter painkillers like Advil and aspirin may help men stave off prostate problems, according to two new studies. However, medical experts are quick to warn men not to self-medicate, and especially not to take more than recommended dosages.

The preventive painkillers fall into the general class of drugs called “non-steroidal anti-inflammatory drugs” or NSAIDs. Ibuprofen is one, and well-known brands include Advil, Motrin, and Nuprin. Other members of the NSAIDs class are naproxen (brand name “Aleve”) and aspirin.

“Our data suggest if men are taking these [medications] for another problem, it might prevent urological problems as well,” Mayo Clinic epidemiologist Jennifer St. Sauver told HealthDay News. St. Sauver’s study showed that men who took NSAIDs on a daily basis reduced the enlargement of their prostate glands by about 50 percent. Such enlargement, called “benign prostatic hyperplasia” or BPH, is common in men over forty, affecting about 50 percent of men by age 50, and about 75 percent by age 80.

The other study was led by Dr. Eric A. Singer, who is chief resident in urology at the University of Rochester Medical Center in New York. Singer’s team found that NSAIDs lowered PSA (prostate specific antigen) levels by about 10 percent. PSA, which is produced by the cells of the prostate gland and is normally present in small amounts, is frequently elevated by disorders of the prostate, including prostate cancer. Some of the men in Singer’s study took acetaminophen (brand name “Tylenol”), which also apparently reduced PSA levels. However, not enough men in the study took it to be statistically significant.

Both St. Sauver and Singer speculated that NSAID’s anti-inflammatory action was the probable role-player in helping prevent prostate problems. Both researchers also caution men that NSAIDs can trigger kidney ailments, liver toxicity, and other health problems. “We are certainly not telling men to take NSAIDs to reduce PSA or cancer risk,” Singer said. “Talk to your health-care provider about prostate health and prostate cancer screening, and make sure your doctor knows what medications you are taking.”
According to the American Cancer Society, close to 200,000 men in the U.S. are diagnosed with prostate cancer every year, and one in six men develop it at some point in their life.

Prognostic significance of 5-year PSA value for predicting prostate cancer recurrence

2009-06-22T11:20:00.001-05:00

PURPOSE: To analyze the prognosis and outcomes of patients who remain free of biochemical failure during the first 5 years after treatment.

METHODS AND MATERIALS: Between 1991 and 2002, 742 patients with prostate cancer were treated with brachytherapy alone (n = 306), brachytherapy and hormonal therapy (n = 212), or combined implantation and external beam radiotherapy (with or without hormonal therapy; n = 224). These patients were free of biochemical failure (American Society for Therapeutic Radiology and Oncology [ASTRO] definition) during the first 5 post-treatment years and had a documented 5-year prostate-specific antigen (PSA) value. The median follow-up was 6.93 years.

RESULTS: The actuarial 10-year freedom from PSA failure rate was 97% using the ASTRO definition and 95% using the Phoenix definition. The median 5-year PSA level was 0.03 ng/mL (range, 0-3.6). The 5-year PSA value was 0.01-0.10 in 31.1%, >0.10-0.2 in 10.2%, >0.2-0.5 in 7.82%, and >0.5 in 3.10%. The 5-year PSA value had prognostic significance, with a PSA value of or=0.2 ng/mL (n = 81; p < .0001). The treatment regimen had no effect on biochemical failure. None of the 742 patients in this study developed metastatic disease or died of prostate cancer.

CONCLUSION: The results of this study have shown that the prognosis for patients treated with brachytherapy and who remain biochemically free of disease for >or=5 years is excellent and none developed metastatic disease during the first 10 years after treatment. The 5-year PSA value is prognostic, and patients with a PSA value <0.2 ng/mL are unlikely to develop subsequent biochemical relapse

Stock RG, Klein TJ, Cesaretti JA, Stone NN.
Department of Radiation Oncology, Mount Sinai Hospital, New York, NY 10029, USA

Characteristics and outcome of prostate cancer with PSA <4 ng/ml at diagnosis: a population-based study

2009-05-20T15:45:00.000-05:00

Division of Radiation Oncology, Geneva University Hospitals, Geneva, Switzerland.

This population-based study aims to assess prognosis of prostate cancer diagnosed with prostate-specific antigen (PSA) levels <4 ng/ml in routine care. Materials and methods We compared prostate cancer patients with low PSA values (n=59) with other prostate cancer patients (n=1330) by logistic regression and the Cox model using data from the Geneva Cancer Registry. Results Patients with low PSA values more frequently had early-stage and well differentiated tumours. Nevertheless, 35% presented with aggressive tumour characteristics or metastases. After adjustment for other prognostic factors, prostate cancer-specific mortality was similar for both groups (hazard ratio: 1.1; 95%CI: 0.6-2.2). Conclusion We conclude that cancer with low PSA values at diagnosis is not indolent.

Strategy for sensitive and specific detection of molecular forms of PSA based on 2DE and kinetic analysis: A step towards diagnosis of prostate canc

2009-01-03T10:55:00.003-06:00

Clin Chim Acta. 2008 Dec 3.
Kumar V, Hassan MI, Singh AK, Dey S, Singh TP, Yadav S.

BACKGROUND: Prostate specific antigen (PSA) present in human seminal fluid exists in many isoforms due to different sequence, glycosylation pattern and polypeptide length. Its presence in various stages of cancer has already been reported. METHODS: We identified 8 forms of Prostate specific antigen followed by purification of 3 forms. We compared their binding affinities to designed synthetic peptides, by using surface plasmon resonance (SPR). PSA forms were purified using various chromatographic procedures and characterized by 2D gel electrophoresis (2DE), matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) and sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). RESULTS: The heterogeneity of purified PSA was demonstrated by 2DE analysis. The peptides were designed on the basis of cleavage map of insulin-like growth factor binding protein 3 (IGFBP-3) subsequently, these peptides showed the binding affinities in the range of 10(-5) to 10(-12) M. Out of 7 peptides, VLLH showed maximum affinity to intact PSA, while FLSYK showed maximum affinity to cleaved forms of PSA. On the other hand, FLSYK in the presence of zinc showed higher affinity to intact PSA. These peptides showed higher affinity to PSA compared to zinc, which is a known inhibitor of PSA. CONCLUSIONS: This study reports purification and characterization of 3 forms of PSA simultaneously. Furthermore, we have reported specific peptides for different forms of PSA which are either responsible for prostate cancer (PCa) or benign prostatic hyperplasia (BPH). Our study aids the existing information on categorizing the molecular heterogeneity of PSA

Prostate-specific antigen detection by using a reusable amperometric immunosensor based on reversible binding and leasing of HRP-anti-PSA from phenylb

2008-07-31T16:45:00.001-05:00

Background
In recent years, many automated immunoassay analyzers have been developed for accurate diagnosis of various disease states and to improve effective drug administration. Amperometric immunoassay has been increasingly applied to laboratory medicine due to its ease in automation, rapid speed and low detection limits. It is important to develop reusable immunologically-sensitive elements for prostate-specific antigen (PSA) detection.

Methods
The strategy for the immunosensor construction is based on the enzyme-conjugated prostate-specific antibody (HRP-anti-PSA) reversible binding with a self-assembled phenylboronic acid monolayer on gold.

Results
After incubating an HRP-anti-PSA modified electrode in a prostate-specific antigen (PSA) solution, a decrease in the electrocatalytic response of the HRP-anti-PSA modified electrode to the reduction of H2O2 is observed. The photometric activity assays show that this decrease of the electrocatalytic response arises from the formation of immunocomplexes of HRP-conjugated anti-PSA and its antigen, not from the loss of bound HRP-anti-PSA from the electrode surface. Analytical performances and optimal conditions of the described immunosensor are also investigated. Under the optimal conditions, the amperometric immunosensor shows a linear increase of the relative intensity in 2 PSA concentration range from 2 to 15 ng/ml and 15 to 120 ng/ml, respectively.

Conclusion
This method could be used for rapid analysis of prostate-specific antigen (PSA) and potentially other antigens.

ARTICLE

Negative influence of changing biopsy practice patterns on the predictive value of prostate-specific antigen for cancer detection on prostate biopsy.

2008-07-10T14:48:00.001-05:00

BACKGROUND: A correlation between prostate specific antigen (PSA) level and positive prostate biopsy rate was established in an era when biopsy practice patterns were different from what they are today. We evaluated if changes in biopsy practice patterns have affected the ability of PSA to predict cancer detection on prostate biopsy in the current era.

METHODS: Of 3634 prostate biopsies performed from 1993-2005, 1607 met criteria for analysis. Biopsy data were divided into 3 time-cohorts (1993-1997, 1998-2001, and 2002-2005) to assess for practice patterns shifts and correlation between PSA and biopsy results.

RESULTS: Significant changes in biopsy practice patterns included an increase in biopsy cores and more frequent use of PSA 2.5-3.99 ng/mL as a biopsy indication. In men with normal DRE, a moderate correlation between PSA and positive biopsy rate did exist from 1993-1997, but was subsequently lost. On multivariate analysis, prostate specific antigen (PSA) was not a significant predictor of biopsy result in men with normal DRE.

CONCLUSIONS: Early in the PSA era, the predictive power of PSA depended on multiple factors: high prevalence of disease, higher prevalence of high-grade disease, and low likelihood of prostate cancer diagnosis in men with low PSA. Now, beyond the culling effect of increased biopsy incidence and with shifted biopsy practice patterns, the correlation between PSA and biopsy result is lost in men with normal DRE. Diagnosing a higher proportion of tumors in men with a PSA between 2.0-4.0 ng/mL has negatively influenced the predictive value of prostate specific antigen (PSA) for cancer detection.

Hierarchical Changepoint Models for Biochemical Markers Illustratedby Tracking Postradiotherapy Prostate-Specific Antigen Series inMen With Prostate C

2008-07-02T13:14:00.002-05:00

PURPOSE: Biomarkers provide valuable information when detecting disease onset or monitoring diseaseprogression; examples include bone mineral density (for osteoporosis), cholesterol (for coronary artery dis-eases), or prostate-specific antigens (PSA, for prostate cancer). Characteristics of markers series can then beused as prognostic factors of disease progression, such as the postradiotherapy PSA doubling time in mentreated for prostate cancer. The statistical analysis of such data has to incorporate the within and be-tween-series variabilities, the complex patterns of the series over time, the unbalanced format of thedata, and the possibly nonconstant precision of the measurements.

METHODS: We base our analysis on a population-based cohort of 470 men treated with radiotherapy forprostate cancer; after treatment, the log2PSA concentrations follow a piecewise-linear pattern. We illus-trate the flexibility of Bayesian hierarchical changepoint models by estimating the individual and popula-tion postradiotherapy log2PSA profiles; parameters such as the PSA nadir and the PSA doubling time wereestimated, and their associations with baseline patient characteristics were investigated. The residual PSA variability was modeled as a function of the prostate-specific antigen concentration. For comparison purposes, two alternative models were briefly considered.

RESULTS: Precise estimates of all parameters of the PSA trajectory are provided at both the individualand population levels. Estimates suggest greater PSA variability at lower PSA concentrations, as well as anassociation between shorter PSAdts and greater baseline PSA levels, higher Gleason scores, and older age.

CONCLUSIONS: The use of Bayesian hierarchical changepoint models accommodates multiple com-plex features of longitudinal data, permits realistic modeling of the variability as a function of the markerconcentration, and provides precise estimates of all clinically important parameters. This type of model should be applicable to the study of marker series in other diseases.

ARTICLE

The effect of 5alpha-reductase inhibition with dutasteride and finasteride on bone mineral density, serum lipoproteins, hemoglobin, prostate specific

2008-06-23T11:57:00.003-05:00

PURPOSE: Dutasteride and finasteride are 5alpha-reductase inhibitors that dramatically decrease serum levels of dihydrotestosterone. Because androgens affect bone, lipids, hematopoiesis, prostate and sexual function, we determined the impact of 5alpha-reductase inhibitors on these end points.

MATERIALS AND METHODS: We conducted a randomized, double-blinded, placebo controlled trial of 99 men 18 to 55 years old randomly assigned to receive 0.5 mg dutasteride (33), 5 mg finasteride (34) or placebo (32) daily for 1 year. Bone mineral density was measured at baseline, after 1 year of treatment and 6 months after drug discontinuation. In addition, markers of bone turnover, fasting serum lipoprotein concentrations, hemoglobin and prostate specific antigen were measured at baseline, after 26 and 52 weeks of treatment, and again 24 weeks after drug discontinuation. Sexual function was assessed at these points by a validated questionnaire.

RESULTS: Significant suppression of circulating dihydrotestosterone levels with the administration of dutasteride or finasteride did not significantly affect bone mineral density or markers of bone metabolism. Similarly serum lipoproteins and hemoglobin were unaffected. Serum prostate specific antigen and self-assessed sexual function decreased slightly during treatment with both 5alpha-reductase inhibitors but returned to baseline during followup.

CONCLUSIONS: Profound suppression of circulating serum dihydrotestosterone induced by 5alpha-reductase inhibitors during 1 year does not adversely impact bone, serum lipoproteins or hemoglobin, and has a minimal, reversible effect on serum prostate specific antigen and sexual function in normal men. Circulating dihydrotestosterone does not appear to have a clinically significant role in modulating bone mass, hematopoiesis or lipid metabolism in normal men.

Early Versus Delayed Hormonal Therapy for Prostate Specific Antigen Only Recurrence of Prostate Cancer After Radical Prostatectomy

2008-05-27T16:42:00.004-05:00

Purpose
Hormonal therapy (HT) is the current mainstay of systemic treatment for prostate specific antigen (PSA) only recurrence (PSAR), however, there is virtually no published literature comparing HT to observation in the clinical setting. The goal of this study was to examine the Department of Defense Center for Prostate Disease Research observational database to compare clinical outcomes in men who experienced PSAR after radical prostatectomy by early versus delayed use of HT and by a risk stratified approach.

Materials and Methods
Of 5,382 men in the database who underwent primary radical prostatectomy (RP), 4,967 patients were treated in the PSA-era between 1988 and December 2002. Of those patients 1,352 men who had PSAR (PSA after surgery greater than 0.2 ng/ml) and had postoperative followup greater than 6 months were used as the study cohort. These patients were further divided into an early HT group in which patients (355) received HT after PSA only recurrence but before clinical metastasis and a late HT group for patients (997) who received no HT before clinical metastasis or by current followup. The primary end point was the development of clinical metastases. Of the 1,352 patients with PSAR clinical metastases developed in 103 (7.6%). Patients were also stratified by surgical Gleason sum, PSA doubling time and timing of recurrence. Univariate and multivariate Cox proportional hazard models were used to evaluate the effect of early and late HT on clinical outcome.

Results
Early HT was associated with delayed clinical metastasis in patients with a pathological Gleason sum greater than 7 or PSA doubling time of 12 months or less (Hazards ratio = 2.12, p = 0.01). However, in the overall cohort early HT did not impact clinical metastases. Race, age at RP and PSA at diagnosis had no effect on metastasis-free survival (p >0.05).

Conclusions
The retrospective observational multicenter database analysis demonstrated that early HT administered for PSAR after prior RP was an independent predictor of delayed clinical metastases only for high-risk cases at the current followup. Further study with longer followup and randomized trials are needed to address this important issue

Judd W. Moula, d, Hongyu Wua, Leon Suna, David G. McLeodd, Christopher Amlinge, Timothy Donahueb, Leo Kusudaf, Wade Sextong, Keith O’Reilly, Javier Hernandezh, , Andrew Chungc, and Douglas Soderdahl

Prostate Cancer Vaccine Effective In Mice, Study Shows

2008-02-08T14:18:00.000-06:00

Researchers at the University of Southern California have developed a prostate cancer vaccine that prevented the development of cancer in 90 percent of young mice genetically predestined to develop the disease. In the February 1 issue of Cancer Research, they suggest the same strategy might work for men with rising levels of PSA (prostate specific antigen) , a potential diagnostic indicator of prostate cancer.

By early vaccination, we have basically given these mice life-long protection against a disease they were destined to have," said the study's lead investigator, W. Martin Kast, Ph.D., a professor of Molecular Microbiology & Immunology and Obstetrics & Gynecology at the Norris Comprehensive Cancer Center. "This has never been done before and, with further research, could represent a paradigm shift in the management of human prostate cancer."

Now, men with rising prostate specific antigen PSA levels but no other signs of cancer are advised "watchful waiting" -- no treatment until signs of the cancer appear, Kast says. "But what if instead of a watchful wait, we vaccinate" That could change the course of the disease."

The study findings also represent a new way to think about the use of therapeutic prostate cancer vaccines, Kast says. Vaccines now in testing are designed to treat men whose cancers are advanced and unresponsive to therapy, and results have offered limited clinical benefit, he says. This novel approach targets the precancerous state with the aim of preventing cancer from developing, he says.

The Kast team's preventive vaccine is designed to mount an immune response against prostate stem cell antigen (PSCA), the protein target of some therapeutic vaccines under development. PSCA, a membrane protein, is over-expressed in about one-third of early-stage prostate cancers, but expression ramps up in all prostate tumors as they grow and advance. PSCA is also expressed at low-levels in normal prostate gland tissue as well as in the bladder, colon, kidney and stomach.

The researchers created a prime-boost vaccination scheme using two kinds of vaccines and tested it in 8-week-old mice that were genetically altered to develop prostate cancer later in life. The first vaccine simply delivered a fragment of DNA that coded for PSCA, thus producing an influx of PSCA protein to alert the immune system. The booster shot, given two weeks later, used a modified horse virus to deliver the PSCA gene.

"Confronting the immune system in two different ways forces it to mount a strong response," Kast said.

In the experimental group, two of 20 mice developed prostate cancer at the end of one year, and by contrast, all control mice had died of the disease. Researchers found that mice in the experimental group had all developed very small tumors that did not progress. "There were tiny nodules of prostate cancer in the mice that were surrounded by an army of immune system cells," Kast said. "The vaccination turned the cancer into a chronic, manageable disease."

The vaccination strategy also works with other antigens, Kast says. The researchers recently tried another prostate cancer membrane target and found that after 1.5 years, 65 percent of experimental mice were still alive, and of those that died, the suspected cause was old age.

Crucially, investigators further found that treated mice did not develop autoimmune disease, a side effect that could develop if the vaccine had also targeted PSCA expression in normal cells. "Theoretically, the vaccine could produce a response in any tissue that expresses the antigen, but the fact that PSCA is expressed in such low levels in normal tissue may prevent that complication," he said.

Still, studies in humans are needed to ensure autoimmunity does not develop, Kast says.

"We feel this is a very promising approach," he said. "With just two shots, the vaccine will prime immune cells to be on the lookout for any cell that over-expresses PSCA."

The study was funded by a pre-doctoral training grant from the National Institutes of Health and a grant from the Margaret E. Early Medical Research Trust. Co-authors include researchers from the University of Southern California as well as from AlphaVax, inc., of Research Triangle Park, North Carolina.

Adapted from materials provided by American Association for Cancer Research.

Prostate-Specific Antigen (PSA)

2007-12-20T13:12:00.000-06:00

A prostate-specific antigen (PSA) test measures the amount of prostate-specific antigen in the blood. PSA is released into a man's blood by his prostate gland . Healthy men have low amounts of PSA in the blood. The amount of PSA in the blood normally increases as a man's prostate enlarges with age. PSA may increase as a result of an injury, a digital rectal exam , sexual activity ( ejaculation ), inflammation of the prostate gland ( prostatitis ), or prostate cancer .

Prostate cancer often grows very slowly, without causing major problems. Detecting prostate cancer early and treating it may prevent some health problems and reduce the risk of dying from the cancer. However, some treatments for prostate cancer can cause other problems, such as controlling urination (incontinence) or erection problems (erectile dysfunction). Some men may choose not to have a PSA test or treat prostate cancer if it is detected. For example, a man older than age 75 who has no bothersome symptoms of prostate cancer may choose not to treat the cancer if it is found, so he would not need a PSA test.

Biology of Prostate-Specific Antigen

2007-11-09T08:23:00.000-06:00

Prostate-specific antigen (PSA) is an androgen-regulated serine protease produced by both prostate epithelial cells and prostate cancer (PCa) and is the most commonly used serum marker for cancer. Prostate specific antigen (PSA) is a protein produced by the cells of the prostate gland. Prostate-specific antigen is present in small quantities in the serum of normal men, and is often elevated in the presence of prostate cancer and in other prostate disorders.

PSA is a major protein in semen , where its function is to cleave semenogelins in the seminal coagulum. PSA is secreted into prostatic ducts as an inactive 244–amino acid proenzyme (proPSA) that is activated by cleavage of seven N-terminal amino acids. PSA that enters the circulation intact is rapidly bound by protease inhibitors, primarily alpha1-antichymotrypsin, although a fraction is inactivated in the lumen by proteolysis and circulates as free PSA

A PSA blood test is the most effective test currently available for the early detection of prostate cancer. Higher than normal levels of PSA are associated with both localized and metastatic prostate cancer (CaP).

Prostate-specific antigen (PSA), also known as kallikrein III, seminin, semenogelase, γ-seminoprotein and P-30 antigen is a 34 kD glycoprotein manufactured almost exclusively by the prostate gland; PSA is produced for the ejaculate where it liquifies the semen and allows sperm to swim freely. It is also believed to be instrumental in dissolving the cervical mucous cap, allowing the entry of sperm.

In addition to measuring human Prostate Specific Antigen in blood, tissue samples can be stained for the presence of PSA in order to determine the origin of maligant cells that have metastasized.

Prostate-Specific Antigen Levels as a Predictor of Lethal Prostate Cancer

2007-10-19T08:36:00.000-05:00

Prostate-Specific Antigen Levels as a Predictor of Lethal Prostate Cancer . Rates of long-term survival among patients with untreated localized prostate cancer are high. To avoid unnecessary treatment, tools are needed to identify the small proportion of patients who are destined to develop lethal prostate cancer. Conclusions: Although baseline PSA value and rate of PSA change are prognostic factors for lethal prostate cancer, they are poor predictors of lethal prostate cancer among patients with localized prostate cancer who are managed by watchful waiting. Source: Journal of the National Cancer Institute 2007 99(7):526-532; doi:10.1093/jnci/djk110

Human Prostate Specific Antigen and Acid Phosphatase Cancer Research Needs

2007-09-24T14:37:00.001-05:00

Lee Biosolutions specializes in the development and purification of high quality BioMarkers for the Immunodiagnostic, clinical diagnostic and pharmaceutical industry worldwide. Demand for high quality human semen proteins such as Human Prostate Specific Antigen and Human Acid Phosphatase PAP has increased significantly due to increase cancer research. As a result we have had collect over 10 liters of Human Semen every year to meet this demand from qualified donors.

Human Tumor Marker PSA has been highly purified to meet current human prostate cancer research requirements. Human Prostate specific antigen is a protein produced by the cells of the prostate gland and Prostate Specific Antigen is highly specific for prostatic tissue.

Human tumor marker Human Prostate Specific Antigen is present in small quantities in the serum of normal men, and is often elevated in the presence of prostate cancer and in other prostate disorders. A blood test to measure Human Prostate Specific Antigen is the most effective test currently available for the early detection of prostate cancer.

Lee Biosolutions has also added matched polyclonal antibodies such as, PSA Antibody to the product line.