PROSTATE CANCER

Vaginal Prostate Specific Antigen (PSA) Is a Useful Biomarker of Semen Exposure Among HIV-Infected Ugandan Women

noreply@blogger.com (Unknown) — Tue, 01 Nov 2016 16:39:00 +0000

Woolf-King, S.E., Muyindike, W., Hobbs, M.M. et al. AIDS Behav (2016). doi:10.1007/s10461-016-1433-7

Abstract

The practical feasibility of using prostate specific antigen (PSA) as a biomarker of semen exposure was examined among HIV-infected Ugandan women. Vaginal fluids were obtained with self-collected swabs and a qualitative rapid test (ABAcard^®p30) was used to detect PSA. Trained laboratory technicians processed samples on-site and positive PSA tests were compared to self-reported unprotected vaginal sex (UVS) in the last 48 h. A total of 77 women submitted 126 samples for PSA testing at up to three study visits. Of these samples, 31 % (n = 39/126) were PSA positive, and 64 % (n = 25/39) of the positive PSA samples were accompanied by self-report of no UVS at the study visit the PSA was collected. There were no reported difficulties with specimen collection, storage, or processing. These findings provide preliminary data on high levels of misreported UVS among HIV-infected Ugandan women using practically feasible methods for PSA collection and processing.

How women can help men spot symptoms of prostate cancer

noreply@blogger.com (Unknown) — Mon, 14 Apr 2014 16:41:00 +0000

From: Louisa Peacock. from the Telegraph

As male patients are being given false hope on prostate cancer, Louisa Peacock outlines how wives and girlfriends can help their male partners spot the disease.

Prostate cancer is very tricky to spot. In some cases, the symptoms may develop over a number of years. In other patients, by the time symptoms become noticeable, prostate cancer has already spread to their bones.

Most men with early prostate cancer do not have symptoms, the charity points out.

However, there are some warning signs for men, because men routinely risk their health by failing to go and see the doctor, their partners can often encourage them to go and get symptoms checked before it's too late.

Symptoms to look out for:
- Having to get up in the night several times to empty your bladder, which you wouldn't normally do

- Having trouble starting to urinate
- Feeling as though the bladder isn't emptying properly
- Dribbling after urinating

Fear of the doctor
A recent study by the National Pharmacy Association showed that nearly nine in 10 men don't like to trouble a doctor unless they have a "serious problem". This reticence has largely been attributed to men’s fear of the doctor, (white coat syndrome) and male machismo.
Partners, wives or girlfriends of men should encourage their loved one to get checked if they notice any unusual bathroom habits.
Historically, women have usually been the custodians of health in the family. Mums, grandmothers, sisters, aunts – have typically been the ones to make their men visit health professionals and sort any kind of ill health out proactively.
Women can help men quell the irrational fear of going to the doctor, so they can seek help before it's too late.
Where prostate cancer has already spread to the bones, the symptoms can include long standing pain in one area, such as the back or pelvic bones.
However, this could be a sign of another illness, such as arthritis.
Blood in semen or in urine could indicate prostate or urine infection, or prostate cancer, he adds. Either way, you're advised to check it out.

Heart disease may be a risk factor for prostate cancer

noreply@blogger.com (Unknown) — Thu, 09 Feb 2012 15:39:00 +0000

Published: Wednesday, February 8, 2012 - 15:36 in Health & Medicine
In a large analysis of men participating in a prostate drug trial, researchers at the Duke Cancer Institute found a significant correlation between coronary artery disease and prostate cancer, suggesting the two conditions may have shared causes. If confirmed that heart disease is a risk factor for prostate cancer, the malignancy might be combated in part by lifestyle changes such as weight loss, exercise and a healthy diet, which are known to prevent heart disease.

"What's good for the heart may be good for the prostate," said Jean-Alfred Thomas II, MD, a post-doctoral fellow in the Division of Urology at Duke and lead author of the study, which appears online this month in the journal Cancer Epidemiology, Biomarkers & Prevention.

Coronary artery disease kills more adults in the United States than any other cause, accounting for one in four deaths. Risk factors include inactivity, obesity, high blood pressure and cholesterol, cigarette smoking, and diabetes.

Similarly, prostate cancer is a common killer. It's the second-most lethal cancer for U.S. men, behind lung cancer, with about 240,000 new cases diagnosed a year, and 34,000 deaths. Previous studies exploring the relationship between coronary artery disease and prostate cancer risk have found conflicting results, making it difficult to determine whether the malignancy is fueled by poor lifestyle choices.

In the current study, the Duke team used data from 6,390 men enrolled in a large study called REDUCE, a four-year, randomized trial to test the prostate cancer risk reduction benefits of a drug called dutasteride. All the study participants had a prostate biopsy at the two- and four-year marks, regardless of their PSA levels. They also provided a detailed medical history that included their weight, incidence of heart disease, alcohol intake, medication use, and other factors.

Among the men in the study, 547 reported a pre-enrollment history of coronary artery disease. This group of men tended to be older, heavier and less healthy, with higher baseline PSA levels, plus more diabetes, hypertension, and high cholesterol. The men were also much more likely to develop prostate cancer, even after accounting for all the baseline differences.

Having coronary artery disease increased the men's risk of prostate cancer by 35 percent, with the risk rising over time. The group was 24 percent more likely to be diagnosed with prostate cancer within the first two years of the study than men who reported no heart disease, and by four years into the study, this group's prostate cancer risk was 74 percent higher.

"We controlled for a number of risk factors, including hypertension, taking statins, or aspirin," Thomas said. "We don't have a good grasp on what's causing the link, but we are observing this association."

Stephen Freedland, MD, associate professor of surgery and pathology in the Division of Urology at Duke and senior author of the paper, said the study had some shortcomings. Notably, it relied on data from a previous trial that didn't account for factors such as diet, physical activity and severity of heart disease that may have influenced the results.

But Freedland said the study eliminated a screening bias common in previous findings that correlated prostate cancer and heart disease using men with high PSA levels.

"This is giving us a lot of good ideas for what to look at next," Freedland said, noting that the overlap between prostate cancer and other diseases associated with poor health habits is a focus of his research group.

In addition to Thomas and Freedland, study authors from Duke include Leah Gerber; Lionel L. Bañez; and Daniel M. Moreira. The Duke authors also hold positions in the surgery section of the Durham VA Medical Center. Study author Roger S. Rittmaster is from GlaxoSmithKline; Gerald L. Andriole is from Washington University School of Medicine in St. Louis.

Source: Duke University Medical Center

he genomic complexity of primary human prostate cancer

noreply@blogger.com (Unknown) — Mon, 09 May 2011 20:29:00 +0000

Prostate cancer is the second most common cause of male cancer deaths in the United States. However, the full range of prostate cancer genomic alterations is incompletely characterized. Here we present the complete sequence of seven primary human prostate cancers and their paired normal counterparts. Several tumours contained complex chains of balanced (that is, ‘copy-neutral’) rearrangements that occurred within or adjacent to known cancer genes. Rearrangement breakpoints were enriched near open chromatin, androgen receptor and ERG DNA binding sites in the setting of the ETS gene fusion TMPRSS2–ERG, but inversely correlated with these regions in tumours lacking ETS fusions. This observation suggests a link between chromatin or transcriptional regulation and the genesis of genomic aberrations. Three tumours contained rearrangements that disrupted CADM2, and four harboured events disrupting either PTEN (unbalanced events), a prostate tumour suppressor, or MAGI2 (balanced events), a PTEN interacting protein not previously implicated in prostate tumorigenesis. Thus, genomic rearrangements may arise from transcriptional or chromatin aberrancies and engage prostate tumorigenic mechanisms.
Nature
Volume:
470,
Pages:
214–220
Date published:

Prostate Specific Antigen Mass Ratio Potential as a Prostate Cancer Screening Tool

noreply@blogger.com (Unknown) — Thu, 16 Sep 2010 16:18:00 +0000

Purpose
Studies suggest lowering the threshold of the prostate specific antigen test in obese men due to the hemodilution effect but prostate specific antigen may be affected by prostate volume and insulin resistance, which also increase with obesity. Thus, we examined the combined effect of these factors on prostate specific antigen.

Materials and Methods
We analyzed 3,461 Korean men 30 to 80 years old with prostate volume data available who underwent routine evaluation. We examined the effect of plasma volume, homeostatic model assessment index, prostate volume and body mass index on prostate specific antigen, and prostate specific antigen mass and mass ratio (total circulating prostate specific antigen protein per prostate volume) by the trend test and/or ANOVA after adjusting for age and/or prostate volume.

Results
Body mass index had positive associations with plasma volume, the homeostatic model assessment index and prostate volume (p for trend <0.01). Prostate specific antigen had a positive association with prostate volume and a negative association with plasma volume (p for trend <0.01) but not with homeostatic model assessment index. The adjusted R2 of prostate volume vs prostate specific antigen was greater than for plasma volume vs prostate specific antigen while for body mass index vs prostate volume it was less than for body mass index vs plasma volume (0.0892, 0.0235, 0.1346 and 0.3360, respectively). Prostate specific antigen mass was not associated with plasma volume or body mass index but it was still associated with prostate volume after adjusting for plasma volume or body mass index (p for trend <0.01). Mean prostate specific antigen mass ratio did not change significantly across body mass index, plasma volume or prostate volume quartiles in men older than 55 years.

Conclusions
It is not logical to lower the prostate specific antigen threshold based on only the hemodilution effect since body mass index related prostate volume enlargement can increase prostate specific antigen in obese men. Another tool is needed and prostate specific antigen mass ratio may be an option.

Volume 184, Issue 2, Pages 488-493 (August 2010)

prostate Specific Antigen Mass Ratio Potential as a Prostate Cancer Screening Tool

Ho-Chun Choi, Jin-Ho Park, Be-Long Cho, Ki-Young Son, Hyuk-Tae Kwon

Bone-marker levels in patients with prostate cancer: Potential correlations with outcomes

noreply@blogger.com (Unknown) — Mon, 28 Jun 2010 19:21:00 +0000

Centre Hospitalier de l'Université de Montréal, Montreal, Quebec, Canada.

Milton S. Hershey Medical Center, Pennsylvania State University Cancer Institute, Hershey, Pennsylvania, USA.

The skeleton is typically the first site of metastasis in patients with prostate cancer, and bone metastases can result in severe bone pain and potentially debilitating fractures. Although bone scans are a reliable means of assessing osteoblastic lesions, tools for monitoring early changes in bone health are lacking. Biochemical markers of bone turnover might fulfill this unmet need.

Correlative studies have suggested that bone-marker levels may have utility in assessing disease progression and response to bone-directed therapy. Elevated levels of the markers, N-telopeptide of type I collagen and bone-specific alkaline phosphatase, are associated with higher rates of death and skeletal-related events in the bone metastasis setting. Marker levels also correlate with response to zoledronic acid treatment, and similar data with the investigational agent, denosumab, are emerging.

Changes in bone-marker levels reflect alterations in skeletal homeostasis and can provide important insights into bone disease progression and response to bone-directed therapy in patients with prostate cancer. More mature data from currently ongoing clinical trials will provide further insight on the utility of marker assessments as an adjunct to established monitoring methods in prostate cancer.

Written by:
Saad F, Lipton A

Prostate Cancer Treatments

noreply@blogger.com (Unknown) — Wed, 10 Feb 2010 23:05:00 +0000

Different types of treatment are available for prostate cancer. You and your doctor will decide which treatment is right for you. Some common treatments are—

•Active surveillance (watchful waiting): This consists of closely monitoring the patient's prostate cancer by performing the PSA and DRE tests regularly, and treating it only if and when the prostate cancer causes symptoms or shows signs of growing.
•Surgery (radical prostatectomy): Prostatectomy is surgery to remove the prostate completely. Radical prostatectomy removes the prostate as well as the surrounding tissue.
•Radiation therapy: Radiation destroys cancer cells, or prevents them from growing, by directing high-energy X-rays (radiation) at the prostate. There are two types of radiation therapy—
◦External radiation therapy: A machine outside the body directs radiation at the cancer cells.
◦Internal radiation therapy (brachytherapy): Radioactive seeds or pellets are surgically placed into or near the cancer to destroy the cancer cells.
•Hormone therapy: This treatment uses drugs, surgery, or other hormones to remove male sex hormones or block them from working, which prevents cancer cells from growing.
Other therapies used in the treatment of prostate cancer that are still under investigation include—

•Cryotherapy: Placing a special probe inside or near the prostate cancer to freeze and kill the cancer cells.
•Chemotherapy: Using special drugs to shrink or kill the cancer. The drugs can be pills you take or medicines given through an intravenous (IV) tube, or, sometimes, both.
•Biological therapy: This treatment works with your body's immune system to help it fight cancer or to control side effects from other cancer treatments. Side effects are how your body reacts to drugs or other treatments. Biological therapy is different from chemotherapy, which attacks cancer cells directly.
•High-intensity focused ultrasound: This therapy directs high-energy sound waves (ultrasound) at the cancer to kill cancer cells.
For more information, visit the National Cancer Institute's (NCI) Prostate Cancer Treatment Option Overview. This site can also help you find a doctor or treatment facility that works in cancer care. Visit Facing Forward: Life After Cancer Treatment for more information about treatment and links that can help with treatment choices.

Clinical Trials
If you have prostate cancer, you may want to take part in a clinical trial. Clinical trials are research studies that help find new treatment options. Visit the NCI and National Institutes of Health (NIH) sites listed below for more information about finding clinical trials.

•Introduction to Clinical Trials (NCI)
•Search for Clinical Trials (NCI)
•ClinicalTrials.gov (NIH)
Complementary and Alternative Medicine
Complementary medicine is a group of medicines and practices that may be used in addition to the standard treatments for cancer. Alternative medicine means practices or medicines that are used instead of the usual, or standard, ways of treating cancer. Examples of complementary and alternative medicine are meditation, yoga, and dietary supplements like vitamins and herbs.

Complementary and alternative medicine does not treat prostate cancer, but may help lessen the side effects of the cancer treatments or of the cancer symptoms. It is important to note that many forms of complementary and alternative medicines have not been scientifically tested and may not be safe. Talk to your doctor before you start any kind of complementary or alternative medicine.

For more information about complementary and alternative medicine, visit NCI's Complementary and Alternative Medicine.

Which Treatment Is Right for Me?
Choosing which kind of treatment is right for you may be hard. If you have prostate cancer, be sure to talk to your doctor about the treatment options available for your type and stage of cancer. Doctors can explain the risks and benefits of each treatment and their side effects.

Sometimes people get an opinion from more than one doctor. This is called a "second opinion." Getting a second opinion may help you choose the treatment option that is right for you.

The natural history of metastatic progression in men with PSA-recurrent prostate cancer after radical prostatectomy: 25-year follow-up

noreply@blogger.com (Unknown) — Tue, 24 Nov 2009 19:26:00 +0000

Journal of Clinical Oncology, 2009 ASCO Annual Meeting Proceedings (Post-Meeting Edition).
Vol 27, No 15S (May 20 Supplement), 2009: 5008

Background: In men with prostate specific antigen (PSA) recurrence following radical prostatectomy (RP) and no other therapy, the natural history of metastatic progression was previously described in 1999.

We now report data reflecting up to 25 years of follow-up. Methods: We performed a retrospective analysis of 774 men treated with RP between 4/1982 and 7/2008 who developed PSA recurrence (>0.2 ng/ml) and never received adjuvant or salvage therapy.

We investigated factors influencing the development of metastases. Results: Mean follow-up after RP was 8.5 y (median 8 y). Of 774 men with PSA recurrence, 295 (38%) developed metastases, and 433 had data on PSA doubling time (PSADT), forming our cohort. The mean time from RP to PSA recurrence in the entire cohort was 4.2 y (median 3 y). In those who developed metastases, the mean time from PSA recurrence to metastasis was 3.1 y (median 2 y). The mean PSA at the time of metastasis was 90.3 ng/ml (median 31.4 ng/ml). In Cox regression analysis: PSADT, Gleason score, and time to PSA progression were predictive of the development of metastases (Table).

In Kaplan-Meier survival analysis, the median actuarial time from PSA recurrence to metastasis was 10 y (95% CI 9 - 15 y). Median actuarial metastasis-free survival from PSA recurrence for men with PSADT <3 mo, 3 - 8.9 mo, 9 - 14.9 mo, and >15 mo was 1 y (95% CI 0 - 1 y), 4 y (95% CI 2 - 6 y), 9 y (95% CI 7 - 13 y), and 15 y (95% CI 12 - 20 y), respectively.

Conclusions: PSADT, Gleason score, and time to PSA progression are strong independent predictors of metastasis-free survival in men with PSA-recurrent prostate cancer. These data facilitate patient counseling and logical risk-based treatment planning. They also provide the background for appropriate selection of patients, treatments, and endpoints for clinical trials

Time Between Treatment And PSA Recurrence Predicts Death From Prostate Cancer

noreply@blogger.com (Unknown) — Wed, 18 Nov 2009 21:13:00 +0000

Time Between Treatment And PSA Recurrence Predicts Death From Prostate Cancer

ScienceDaily (Nov. 9, 2009) — Men whose prostate specific antigen (PSA) rise within 18 months of radiotherapy are more likely to develop spread and die of their disease, according to an international study led by Fox Chase Cancer Center radiation oncologist Mark K. Buyyounouski, M.D., M.S. and presented today at the annual meeting of the American Society for Radiation Oncology (ASTRO).

"PSA is the gold standard for following prostate cancer patients after they receive radiation or surgery. But we haven't know if having prostate specific antigen (PSA) rise sooner means a patient has a greater danger of dying of prostate cancer, though it seems logical," Buyyounouski says.

Using a single institution database, Buyyounouski and colleagues showed previously that men who suffered an early biochemical failure, which is defined as their lowest PSA level plus 2 ng/mL, were at greater risk of dying of prostate cancer. The new study confirms those results using a multinational database and shows that the measure is ready for use in the clinic.

"Now we can use the simple criteria from this study, which is widely available for anyone who has PSA testing, to identify men who have a greater than 25% chance of dying from prostate cancer in the next five years. That is huge. There is nothing else that can do that," says Buyyounouski.

A total of 2,132 men with clinically localized prostate cancer who suffered biochemical failure after treatment were studied. The median interval between treatment and biochemical failure was 35.2 months for the entire study group. However, 19% of patients developed biochemical failure at 18 months or less. The five-year cancer-specific survival for these men was 69.5% compared with 89.8% for men who developed biochemical failure after 18 months.

A multivariate analysis showed that the interval to biochemical failure correlated with cancer specific survival, as did Gleason score, tumor stage, age, and PSA doubling time. However, the interval to biochemical failure had the best predictive value for cancer-specific mortality, compared with the other variables.

Currently, most physicians do not start treatment based on biochemical failure alone, but rather wait until the PSA reaches a high level or there is some other evidence tumor spread. "The potential impact of this finding is that patients can initiate treatment far sooner without waiting for other signs or symptoms of prostate cancer," Buyyounouski says. "If a patient has biochemical failure at 16 months, rather than wait and learn later that the PSA is rising sharply and risk the development of distant metastasis, therapy can be started sooner based on the increased risk of death."

A review of prostate-specific antigen screening prevalence and risk perceptions for first-degree relatives of men with prostate cancer

noreply@blogger.com (Unknown) — Thu, 20 Aug 2009 16:20:00 +0000

McDowell ME, Occhipinti S, Gardiner RA, Baade PD, Steginga SK.
School of Psychology, Griffith University, Brisbane, Australia.

First-degree relatives of men with prostate cancer have a higher risk of being diagnosed with prostate cancer than men without a family history. The present review examines the prevalence and predictors of testing in first-degree relatives, perceptions of risk, prostate cancer knowledge and psychological consequences of screening. Medline, PsycInfo and Cinahl databases were searched for articles examining risk perceptions or screening practices of first-degree relatives of men with prostate cancer for the period of 1990 to August 2007. Eighteen studies were eligible for inclusion. First-degree relatives participated in Prostate Specific Antigen (PSA) testing more and perceived their risk of prostate cancer to be higher than men without a family history. Family history factors (e.g. being an unaffected son rather than an unaffected brother) were consistent predictors of PSA testing. Studies were characterized by sampling biases and a lack of longitudinal assessments. Prospective, longitudinal assessments with well-validated and comprehensive measures are needed to identify factors that cue the uptake of screening and from this develop an evidence base for decision support. Men with a family history may benefit from targeted communication about the risks and benefits of prostate cancer testing that responds to the implications of their heightened risk.

Transcriptionally regulated, prostate-targeted gene therapy for prostate cancer.

noreply@blogger.com (Unknown) — Sun, 14 Jun 2009 15:25:00 +0000

Prostate cancer is the most frequently diagnosed cancer and the second leading cause of cancer deaths in American males today. Novel and effective treatment such as gene therapy is greatly desired. The early viral based gene therapy uses tissue-nonspecific promoters, which causes unintended toxicity to other normal tissues. In this chapter, we will review the transcriptionally regulated gene therapy strategy for prostate cancer treatment. We will describe the development of transcriptionally regulated prostate cancer gene therapy in the following areas: (1) Comparison of different routes for best viral delivery to the prostate; (2) Study of transcriptionally regulated, prostate-targeted viral vectors: specificity and activity of the transgene under several different prostate-specific promoters were compared in vitro and in vivo; (3) Selection of therapeutic transgenes and strategies for prostate cancer gene therapy (4) Oncolytic virotherapy for prostate cancer. In addition, the current challenges and future directions in this field are also discussed.
Department of Pathology and Laboratory Medicine, University of Tennessee Health Science Center

Stage-specific cancer incidence: An artificially mixed multinomial logit model.

noreply@blogger.com (Unknown) — Wed, 20 May 2009 19:30:00 +0000

Takeda Global Research & Development Center, Inc., Analytical Sciences, 675 North Field Drive, Lake Forest, IL 60045, U.S.A.

Early detection of prostate cancer using the prostate-specific antigen test led to a sharp spike in the incidence of the disease accompanied by an equally sharp improvement in patient prognoses as evaluated at the point of advanced diagnosis. Observed outcomes represent age at diagnosis and stage, a categorical prognostic variable combining the actual stage and the grade of tumor. The picture is summarized by the stage-specific cancer incidence that represents a joint survival-multinomial response regressed on factors affecting the unobserved history of the disease before diagnosis (mixture). Fitting the complex joint mixed model to large population data is a challenge. We develop a stable and structured MLE approach to the problem allowing for the estimates to be obtained iteratively. Factorization of the likelihood achieved by our method allows us to work with only a fraction of the model dimension at a time. The approach is based on generalized self-consistency and the quasi-EM algorithm used to handle the mixed multinomial part of the response through Poisson likelihood. The model provides a causal link between the screening policy in the population and the stage-specific incidence. Copyright (c) 2009 John Wiley & Sons, Ltd
Stat Med. 2009 May 19.

Prostatic Acid Phosphatase Adversely Affects Cause-Specific Survival in Patients with Intermediate to High-Risk Prostate Cancer Treated with Brachythe

noreply@blogger.com (Unknown) — Wed, 23 Jul 2008 15:31:00 +0000

Objectives
To perform a retrospective analysis to assess the utility of pretreatment serum prostatic acid phosphatase (PAP) as a predictor of cause-specific survival (CSS) in patients with higher risk prostate cancer treated with palladium-103 (103Pd) brachytherapy and supplemental external beam radiotherapy (EBRT).

Methods
From 1992 to 1996, 193 patients with clinically localized prostate adenocarcinoma, a pretreatment PAP level, and Gleason score 7 or more, and/or a prostate-specific antigen (PSA) level of 10 ng/mL or more were treated with 103Pd brachytherapy and supplemental EBRT. The patients underwent EBRT of 41.4 Gy to a limited pelvic field and 103Pd brachytherapy with a prescribed minimum 103Pd dose of 80 Gy. Multivariate analysis was performed to analyze the predictive value of PAP, PSA, and Gleason score on CSS.

Results
The 10-year CSS rate for patients with a PAP level of less than 1.5, 1.5 to 2.4, and 2.5 U/L or more was 93%, 87%, and 75%, respectively (P = 0.013). The 10-year CSS rate for patients with a PSA level of less than 10, 10 to 20, and greater than 20 ng/mL was 92%, 76%, and 83%, respectively (P = 0.393). The 10-year CSS rate for patients with a Gleason score of 6, 7, 8, and 9 was 90%, 89%, 70%, and 68%, respectively (P = 0.002). On Cox multivariate regression analysis, PAP (hazard ratio 1.31, P <0.0001) and Gleason score (hazard ratio 2.37, P = 0.0007) were associated with CSS. PSA was not predictive of CSS (P = 0.393).

Conclusions
The results of this study demonstrated that PAP is a stronger predictor of CSS than PSA or Gleason score in men with higher risk prostate cancer treated with 103Pd brachytherapy and EBRT. Given the findings of this analysis, the use of PAP should be reconsidered in these patients.

Body Mass Index and Prostate-Specific Antigen Failure Following Brachytherapy for Localized Prostate Cancer.

noreply@blogger.com (Unknown) — Wed, 16 Jul 2008 18:46:00 +0000

PURPOSE:
Increasing body mass index (BMI) is associated with prostate-specific antigen (PSA) failure after radical prostatectomy and external beam radiation therapy (EBRT). We investigated whether BMI is associated with PSA failure in men treated with brachytherapy for clinically localized prostate cancer.

PATIENTS AND METHODS:
Retrospective analyses were conducted on 374 patients undergoing brachytherapy for stage T1c-T2cNXM0 prostate cancer from 1996-2001. Forty-nine patients (13%) received supplemental EBRT and 131 (35%) received androgen deprivation therapy (ADT). Height and weight data were available for 353 (94%). Cox regression analyses were performed to evaluate the relationship between body mass index (BMI) and PSA failure (nadir + 2 ng/ml definition). Covariates included age, race, preimplantation prostate-specific antigen (PSA), Gleason score, T category, percent of prescription dose to 90% of the prostate, use of supplemental EBRT, and ADT.

RESULTS:
Median age, PSA, and BMI were 66 years (range, 42-80 years), 5.7 ng/ml (range, 0.4-22.6 ng/ml), and 27.1 kg/m(2) (range, 18.2-53.6 kg/m(2)), respectively. After a median follow-up of 6.0 years (range, 3.0-10.2 years), there were 76 PSA recurrences. The BMI was not associated with PSA failure. Six-year PSA failure rates were 30.2% for men with BMI less than 25 kg/m(2), 19.5% for BMI of 25 or greater to less than 30 kg/m(2), and 14.4% for BMI of 30 kg/m(2) or greater (p = 0.19). Results were similar when BMI was analyzed as a continuous variable, using alternative definitions of PSA failure, and excluding patients treated with EBRT and/or ADT. In multivariate analyses, only baseline PSA was significantly associated with shorter time to PSA failure (adjusted hazard ratio, 1.12; 95% confidence interval, 1.05-1.20; p = 0.0006).

CONCLUSIONS:
Unlike after surgery or EBRT, body mass index (BMI) is not associated with prostate-specific antigen (PSA) failure in men treated with brachytherapy for prostate cancer. This raises the possibility that brachytherapy may be a preferred treatment strategy in obese patients.

Prostate specific antigen versus prostate specific antigen density as a prognosticator of pathological characteristics and biochemical recurrence foll

noreply@blogger.com (Unknown) — Tue, 01 Jul 2008 19:51:00 +0000

PURPOSE: The usefulness of prostate specific antigen (PSA) density for predicting pathological stage and biochemical recurrence after radical prostatectomy has not been well defined. We investigated whether prostate specific antigen density yielded an advantage over total prostate specific antigen for predicting adverse pathological characteristics and disease recurrence following radical prostatectomy.

MATERIALS AND METHODS: A total of 13,434 men who underwent radical prostatectomy for clinically localized prostate cancer between 1984 and 2006 were included in this study. The study population was stratified by Gleason score (6 or less, 7, and 8 or greater), and the clinical and pathological characteristics of each group were compared. We constructed ROC curves and determined the ROC AUC and concordance index to specifically investigate the accuracy of prostate specific antigen (PSA) and prostate specific antigen density for predicting pathological stage and biochemical recurrence.

RESULTS: Prostate specific antigen density was better than prostate specific antigen (PSA)for predicting extraprostatic extension and biochemical-free recurrence in patients with a biopsy Gleason score of 6 or less (each p <0.001). In patients with a biopsy Gleason score of 7 prostate specific antigen was more predictive than prostate specific antigen density for seminal vesicle involvement (p <0.001), lymph node involvement (p = 0.017) and biochemical-free recurrence (p <0.001). In men with a biopsy Gleason score of 8 or greater there was no statistical difference between prostate specific antigen and prostate specific antigen density in terms of prognostic value for pathological or clinical outcomes.

CONCLUSIONS: Prostate specific antigen density is highly associated with pathological stage and biochemical-free survival following radical prostatectomy. In lower grade prostate cancers prostate specific antigen density is significantly more accurate for predicting extraprostatic extension and biochemical-free recurrence compared to total prostate specific antigen. It should be considered when counseling patients on outcomes following radical prostatectomy.

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

noreply@blogger.com (Unknown) — Tue, 17 Jun 2008 21:45:00 +0000

PURPOSE: Biomarkers provide valuable information when detecting disease onset or monitoring diseaseprogression; examples include bone mineral density (for osteoporosis), cholesterol (for coronary artery diseases), 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 illustrate 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 PSA concentration. For comparison purposes, two alternativemodels 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 modelshould be applicable to the study of marker series in other diseases.

CARINE A. BELLERA,PHD, JAMES A. HANLEY,PHD, LAWRENCE JOSEPH,PHD,AND PETER C. ALBERTSEN,MD

PSA velocity does not aid long-term prediction of prostate cancer incidence

noreply@blogger.com (Unknown) — Tue, 17 Jun 2008 21:36:00 +0000

Elevated serum prostate-specific antigen (PSA) levels can indicate the presence of prostate cancer, although PSA levels are also elevated in some nonmalignant conditions, which affects the reliability of prostate cancer prediction. PSA levels rise sharply in patients with aggressive prostate cancer, and a recent study suggested that the rate of increase (PSA velocity) could predict life-threatening prostate cancer 10–15 years before diagnosis. Ulmert and colleagues evaluated data from the Malmö Preventative Medicine population-based study to compare the accuracy of a single PSA measurement versus PSA velocity in the long-term prediction of prostate cancer diagnosis.

Nature Clinical Practice Oncology (2008) 5, 302

Racial Differences in Prostate Cancer Screening by Family History

noreply@blogger.com (Unknown) — Tue, 17 Jun 2008 21:29:00 +0000

Purpose
Prostate cancer (CaP) is disproportionately prevalent among black, compared to white, men. Additionally, men with a family history of CaP have 75% to 80% higher risk of CaP. Therefore we examined racial variation in the association of family history of CaP and self-reported prostate-specific antigen (PSA) testing in the nationally-representative National Health Interview Survey (NHIS).

Methods
Data were obtained from the 2005 NHIS, including the Cancer Control Module supplement. We restricted the study sample to men over the age of 40 who reported having “ever heard of a PSA test” (N = 1,744). Men were considered to have a positive family history if either their biological father or at least one biological brother had been diagnosed with CaP. SUDAAN 9.0 was used to perform descriptive and multivariable logistic regression analyses.

Results
Men with a family history of CaP were more likely to have a PSA test than those who never had a PSA test (odds ratio [OR] = 1.8; 95% confidence interval [CI]: 1.3–2.5). Among blacks, men with a family history were not significantly more likely to have a PSA test.

Conclusions
Despite having the highest risk of cancer, black men with a family history are not screened more than black men without a family history.

Bettina F. Drake MPH, PhDa, Christopher S. Lathan MD, MPHb, Cassandra A. Okechukwu MSN, MPHc and Gary G. Bennett PhD

ARTICLE

Using spectral moments of spiral networks based on PSA/mass spectra outcomes to derive quantitative proteome–disease relationships (QPDRs) and predict

noreply@blogger.com (Unknown) — Mon, 16 Jun 2008 19:55:00 +0000

In prostate cancer (PCa), prognostic (predictive) factors are particularly important given the marked heterogeneity of this disease at clinical, morphologic, and biomolecular levels. Blood contains a treasure of previously unstudied biomarkers that could reflect the ongoing physiological state of all tissue. The serum prostate-specific antigen (PSA) measurement is a very good biomarker for PCa, but the percentage of bad classification is somewhat high. The blood proteome mass spectra (MS) represent a potential tool for detection of diseases; however the identification of a single biomarker from the complex output from MS is often difficult. In this paper, we propose a general strategy, based on computational chemistry techniques, which should improve the predictive power of PSA. Our group adapted the square–spiral graph to represent human serum-plasma–proteome MS for healthy and PCa patients. These graphs were previously applied to DNA and/or protein sequences. In this work, we calculated different classes of connectivity indices (CIs), and created various models based on the spectral moments. The best QPDRs model found showed accuracy values ranging from 71.7% to 97.2%, and 70.4% to 99.2% of specificity. This methodology might be useful for several applications in computational chemistry.

Giulio Ferinoa, Humberto González-Díaza b, Giovanna Delogua, Gianni Poddaa, and Eugenio Uriarteb

ARTICLE

Gene Linked to Deadly Prostate Cancer

noreply@blogger.com (Unknown) — Wed, 05 Mar 2008 16:49:00 +0000

Prostate cancer is common. It's also deadly. About 220,000 men in the United States will learn that they have prostate cancer this year. Despite tests to detect it early and several effective treatments, the disease kills about 27,000 men in the United States each year.

On the other hand, many men with prostate cancer have tiny tumors that pose no significant threat to their health. For these men, early detection and treatment provides no benefit. So, it's a big challenge to learn how to detect the dangerous tumors while leaving the others alone. That's not easy.

To make matters worse, non-cancerous enlargement of the prostate, a nearly universal part of aging for men, may mimic prostate cancer . For example, the prostate-specific antigen (PSA) blood test may be high. This can raise concern about prostate cancer even when no cancer is present.

Clearly, we need better ways to identify men who have early prostate cancer requiring treatment. That's why the results of a new research study from Iceland are notable. The study links a gene mutation to an increased risk of aggressive prostate cancer. Interestingly, the mutation is located on a gene – called BRCA2 – known to increase the risk of cancers of the breast and ovary among women.

In this new research, scientists reviewed cases of prostate cancer in Iceland from the last 50 years. They selected study subjects with prostate cancer who also had female relatives with breast cancer. Researchers discovered that men who carried a particular BRCA2 gene mutation tended to have the worst forms of prostate cancer.

For example, men with the BRCA2 mutation had:

· Onset of prostate cancer at a younger age

· More advanced prostate cancer

· Shorter survival

The effect on survival was particularly striking. On average, those with the mutation lived just 2 years from the time of diagnosis. Non-carriers of the mutation survived more than 12 years.

It's hard to know whether these results will have a big impact on prostate cancer detection or treatment. The mutation was found in less than 6% of study subjects with prostate cancer. The rate might have been lower if these men did not have relatives with breast cancer. This mutation might be even rarer outside Iceland.

Still, the findings suggest that looking for mutations in genes with known links to cancer could provide valuable information. It's easy to imagine that genetic testing could someday be a routine part of screening for prostate cancer (and other cancers). Perhaps the results could be used to predict the need for aggressive treatment.

by Harvard Publications

Link Between Severe Acne and Prostate Cancer

noreply@blogger.com (Unknown) — Tue, 29 Jan 2008 18:44:00 +0000

(Ivanhoe Newswire) A higher risk of prostate cancer may be linked to severe acne.

New research from Johns Hopkins Bloomberg School of Public Health in Baltimore finds men who took tetracycline -- an antibiotic used to treat severe acne -- for four years or longer were 70 percent more likely to develop prostate cancer over a 10-year period than men who had taken the drug, or had taken it for a shorter time.

But the studys authors urge caution in interpreting their findings. They note the small number of participants who had used tetracycline for at least four years -- 0.5-percent of the 34,629 men in the study -- the indirect assessment of severe acne, and the fact that acne can have several causes.

The research looked at the link between severe acne and prostate cancer because recent studies found the acne-related bacterium Propionibacterium acnes in one third of prostate samples taken from men with prostate cancer. The tissue containing P. acnes was more likely to be inflamed. Inflammation is believed to be an important part of the development of prostate cancer.

Researchers say it is unlikely tetracycline itself would raise the risk of prostate cancer . They believe one possible explanation for the acne-prostate cancer link is that men who develop severe acne may be more likely to have stronger inflammatory immune responses when P. acnes goes into the prostate.

SOURCE: International Journal of Cancer, 2007;121:2688-2692

Prostate Specific Antigen

noreply@blogger.com (Unknown) — Fri, 28 Dec 2007 16:04:00 +0000

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

noreply@blogger.com (Unknown) — Thu, 06 Dec 2007 16:44:00 +0000

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. Prostate Specific Antigen 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. PSA 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.

Source:
Steven P. Balk, Yoo-Joung Ko, Glenn J. Bubley
From the Cancer Biology Program, Hematology-Oncology Division, Beth Israel Deaconess Medical Center , Harvard Medical School , Boston, MA.