Tag Archive | "prostate-cancer"

Prostate Cancer and Genetics

Although prostate cancer is the most common cancer found in men, the pathophysiology of this disease remains poorly understood. No definite behavioral or environmental risk factors have been identified, but genetics are an important and likely the strongest contributing factor to the development and progression of the disease. Indeed it has been shown that first degree relatives of affected men are at over two-fold higher risk of developing prostate cancer.

In contrast to other types of cancer, it’s still unclear which individual genes dictate prostate cancer. There are only a few genes with known mutations that cause prostate cancer, and furthermore these mutations explain less than 10% of the risk. Given this, it’s likely that variations in the lower penetrance loci may contribute to disease susceptibility. Multiple case-control genome wide association studies have identified numerous single nucleotide polymorphisms associated with prostate cancer risk. Nevertheless, the problem still lies in how to interpret their combined and individual contributions to disease risk.

Recent studies have examined these potential indicators and have discovered more than 30 loci that may contribute to prostate cancer. However, due to the large number of possible loci, it’s necessary to perform more analyses in a large population of cases and controls testing all of the genetic variants. Hopefully these future studies will reveal a more complete understanding of the individual and cumulative risks associated with these loci.

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Low-Fat Diet May Reduce Risk of Prostate Cancer

According to a study lead by a team of researchers at Jonsson Cancer Center at the University of California, Los Angeles, a diet high in unhealthy types of fats is a potential cause of prostatic diseases, which includes benign prostatic hyperplasia and prostate cancer.

The researchers focused on mice that were fed a diet high in fat from corn oil.  Corn oil is primarily comprised of omega-6 fatty acids, which is the type of polyunsaturated fat found in processed baked goods and fried foods.  This type of fat should not be confused with omega-3 fatty acids, which are the healthiest fats and are found in fish, or monounsaturated fats, which are found in almonds, pecans, cashew nuts, peanuts, avocados, olive oil, and canola oil.

In the study, researchers fed one group of mice a diet with 40 percent of calories coming from fat, which is similar to the amount found in a typical Western diet.  The second group of mice received 12 percent of their caloric intake from fat.  The results showed a 27 percent lower incidence of prostate cancer in the low-fat diet group.  Further, precancerous cells grew at a much slower rate in the low-fat diet group, compared to those in the high-fat group.

In a supplemental study, Dr. Sanjay Gupta, MS, PhD, and colleagues found that high-fat diets actually activate a protein complex which leads to prostatic inflammation.  The researchers noted that when non-obese mice were fed a high-fat diet for four, eight, and 12 weeks, they exhibited significant increases in the protein complex activation, prostate weight, and prostate expression of inflammation when compared with mice that were fed a regular diet.

While most of the information has come from mice studies, researchers say that the finding translates to people.  Human clinical trials will be following shortly to prove that lowering dietary fat intake results in an increase in levels of a protein that slows prostate cancer development by reducing the amount of growth factor that encourages prostate cancer.

“A low-fat, high-fiber diet combined with weight loss and exercise is well known to be healthy in terms of heart disease and is known to reduce the risk of heart attacks and strokes, so that would be a healthy choice to make,” said Dr. William Aronson, a Jonsson Cancer Center researcher and the UCLA study’s senior author.  “Whether or not it will prevent prostate cancer in humans remains to be seen.”

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Chemicals in Plastics May Increase the Risk of Prostate Cancer

A chemical found in babies’ bottles, as well as many other plastics, has been linked to an increased risk of prostate cancer, warns scientists.

In experiments, newborn rats were fed bisphenol A, which is a building block of many commonly used plastics.  The results showed that these rats were more likely to develop pre-cancerous cells as they aged.  Scientists have agreed that rats have chemical levels similar to those commonly found in the human body, and researchers said the findings of the bisphenol A study are directly relevant to babies’ health.

Recently, the Food Standards Agency said that bisphenol A does not carry a risk; however, this most recent study clearly shows that the compound is linked to cancer.  And bisphenol A is found in many of our plastics, including CD cases, tin can linings, sunglasses, plastic knives and forks, mobile phones, and dental sealants.

The American researchers showed that the newborn rats that were fed bisphenol A were more likely to develop cellular damage that can lead to prostate cancer later in life.  And, according to University of Illinois researcher Gail Prins, “There was no difference in the number of lesions, whether the bisphenol A was given by injection or orally, the prostate pathology was the same.  It mattered nothing which way it was given.”

This statement is important because it suggests that the latest research findings are revealing that the damage seen in experiments may span to how we access it through food and drink.

Dr. Prins wrote in the journal Reproductive Toxicology, “These findings on prostate health are directly relevant to humans at current bisphenol A exposure levels…[and] support the proposal that exposures to bisphenol A during fetal and neonatal life may increase the risk of carcinogenic events during adult life and in the human population.”

Elizabeth Salter Green, of the Chemicals, Health and Environment Monitoring Trust, seems to uphold the findings of the study and suggests, “Responsible governments need to find alternatives to bisphenol A as so many consumer products are made using this chemical and we are all constantly exposed.”

Other campaigners are urging people to use bisphenol A-free baby bottles, cut down on their use of canned foods, and opt for glass, porcelain, or stainless steel containers when possible.  In addition, those who are concerned with the findings of the recent bisphenol A rat study should avoid heating foods, including baby meals, in polycarbonate plastic food containers as the chemical has been known to leak out of plastics at high temperatures.

Despite the campaign against bisphenol A, the Prostate Cancer Charity urged people not to worry, citing information that the chemical breaks down much more quickly in the human body than in a rat.  In fact, Dr. Kate Holmes of the charity said, “This is a field of research that remains highly controversial.  Bisphenol A is still considered to be a safe product for use by the food industry and the exposure of humans to this product is considered to be minimal.”

Dr. Holmes insists that the best way to take control of a man’s overall health is to maintain a healthy diet rich in fruit and vegetables while engaging in a physically active lifestyle.  She says, “Moving away from a diet rich in meat and saturated fat will improve overall health and reduce the risk of chronic conditions like heart disease, as well as possibly helping to prevent prostate cancer.”

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Prostate Cancer Patients on ADT Not Affected by Provenge

A recent study, led by Tomasz Beer, MD, Professor of Medicine at Oregon Health & Science University (OHSU) in Portland, Oregon, found that prostate cancer (PCa) patients on androgen deprivation therapy (ADT) and receiving sipuleucel-T (Provenge) have no adverse outcomes in terms of quality of life.  These findings were presented at the 47th Annual Meeting of the American Society of Clinical Oncology.

The study involved 176 men who were placed on ADT for three to four months after experiencing PSA recurrence after radical prostatectomy.  Sipuleucel-T, which received FDA approval for the treatment of late-stage PCa last year, is not usually used in men with earlier states of prostate cancer.  This is the first study to explore the effect of the autologous cellular immunotherapy on quality of life.

After three to four months, ADT was stopped and all men were randomized to treatment with sipuleucel-T (117 patients) or control (59 patients). Using survey techniques, the researchers assessed quality of life at baseline (following ADT and prior to randomization) and at weeks 13 and 26 after treatment.  Ninety-eight percent of subjects completed baseline quality of life assessment and 92% had at least one post-treatment assessment.  During ADT in the three months before sipuleucel-T treatment, quality of life measures decreased comparably in both study arms.  After the start of the study treatment, there were no significant differences found in the quality of life between the two groups.

Dr. Beer emphasized that the results from the study suggest that a larger study in early disease patients is needed.

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Gene Test Effectively Predicts Presence of nearby Prostate Cancer

Data from a large group of tissue samples showed that gene expression in prostate stroma predicted the presence of nearby cancer with 97% overall accuracy.  Stroma adjacent to or near prostate tumors expressed genes significantly differently from normal stroma.

In a recent issue of Cancer Research, it was reported that the correlation between stromal gene expression and cancer increased with proximity to cancer.  The 144-gene panel had 98% sensitivity and 88% specificity for predicting the presence of cancer, whereas, a randomly selected 100-gene panel had no predictive value.  If replicated in additional studies, the gene test has multiple therapeutic implications.

The research team compared gene expression profiles in 13 prostate biopsy specimens containing stroma near tumor and in 15 biopsy specimens from men without prostate cancer and identified 3,800 significant changes in expression.

The authors developed a 114-gene stroma-specific classifier for nearby tumor after filtering for age-related genes and for genes known to be expressed at detectable levels in tumors.  They tested the classifier in 364 prostate specimens, consisting of 243 tumor-bearing samples and 121 normal specimens.  These 364 specimens included samples from normal prostate biopsies, normal prostate tissue obtained from autopsies, stroma remote to tumor, and stroma from within a few millimeters of tumor.  The gene panel correctly identified all but two of the 243 tumor-containing specimens. Analysis of the two misclassifications suggested the tissue might not have come from patients with prostate cancer.

The research team also compared expression patterns in stromal tissue near and far from the tumor and found a gradient of classification frequency values of 98%, 75%, and 36% for stromal samples adjacent to, close to, and remote (>15 mm) from the tumor.

These findings suggest several practical applications of the gene test, such as assessment of suspicious initial biopsies and possibly therapeutic targeting of stromal expression changes indicating the presence of tumor while leaving normal stroma relatively untouched.

Some of the authors of the gene expression study disclosed relationships with Proveri, a company involved in translational research related to the study.

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No Significant Association Found Between Androgen Deprivation Therapy and Cardiovascular Death

Treatment with androgen deprivation therapy (ADT) does not significantly increase the risk of cardiovascular mortality according to evaluation of mortality data in a large registry of men treated for prostate cancer.

ADT is commonly used to treat prostate cancer.  Some studies have shown that it may increase the risk of cardiovascular disease, but other studies have not confirmed the association and it remains controversial.  The authors of the recent study tried to explore the evidence further by analyzing the patients registry CAPSURE (Cancer of the Prostate Strategic Urologic Research Endeavor), which includes men with confirmed prostate cancer recruited from 40 mostly community-based US urological practices.

Men who are diagnosed with localized prostate cancer between 1995 and 2007 were included in the analysis, and in order to try to control for factors that may confound the relationship between ADT and cardiovascular death, patients who used and did not use ADT were matched by their propensity to receive ADT.  These patients were categorized into three groups: primary ADT monotherapy, local treatment plus ADT, and watchful waiting/active surveillance (WW/AS).  Initial outcomes were associations between treatment and cardiovascular cause, prostate cancer, and other causes.  Study investigators assessed cause of death using death certificates.

At the point of data capture, there were 13,887 men in the registry, of whom 7,248 were eligible for the analysis.  The majority (71.3%) received local treatment only, 6.7% received local treatment plus ADT, 15% received primary ADT, and 7 percent WW/AS.  It was found that 21.7% received AFT at some point.  Nine hundred seventy six of these men died during the study period, 1.4% from prostate cancer, 2.7% from cardiovascular disease, and 9.4 percent due to other causes.  Patients treated with ADT or WW/AS had a higher likelihood of death due to prostate cancer than those treated just with local therapy.

The largest risk of cardiovascular death was in those treated with WW/AS compared to those only receiving local therapy.  The difference for those treated with local therapy plus ADT was not significant.

The authors’ conclusion is that the increased rate of cardiovascular death in the WW/AS group compared to the ADT group suggests that there are possibly unmeasured variables that affect treatment selection and that confound the association between ADT and cardiovascular death.  The research team notes that when patients were match on propensity to receive ADT, there was no significant association.  The limitation so the study included the relatively small number of deaths in some groups, and the assignment of cause of death from death certificates.

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Pre-op Counseling For Prostate Surgery Not Effective

Researchers have found that over half of men undergoing radical prostatectomy have unrealistic expectations about some of the outcomes.

Daniela Wittmann, MSW, and colleagues at the University of Michigan Comprehensive Cancer Center in Ann Arbor, Michigan found that despite a pre-operative education program, 61 percent of men expected the same or better sexual function a year after surgery as they had before.  Sixty percent of men expected difficulties with urinary incontinence to be the same or better.  These findings were published in the Journal of Urology.

Wittmann and colleagues found that a substantial proportion of patients, 17 percent and 12 percent, respectively for both effects, expected better performance a year after surgery than before even though they had been told that such an outcome was improbable.  The researchers argued that this finding suggests that pre-op education should be followed up with post-surgery support for prostate cancer survivors.

The research team asked men undergoing radical prostatectomy to fill out the short form of the Expanded Prostate Index Composite questionnaire, both before and a year after surgery to get an idea of their urinary, bowel, hormonal, and sexual function.

The men were also asked, after pre-op counseling but before surgery, to fill out the Expanded Prostate Index Composite-Expectations questionnaire, which detailed what level of function they expected a year later.  Both questionnaires assess five domains: incontinence, urinary irritative symptoms, bowel function, hormonal function, and sexual function.

Analysis of the 152 participants showed that 36 percent and 40 percent expected the same function at one year as at baseline in urinary incontinence and sexual function, respectively, while 12 percent and 17 percent expected better function.  Forty-seven percent and 44 percent of patients had lower than expected function for urinary incontinence and sexual function, respectively.  Expectations matched or were better than outcomes for 78 percent of patients for urinary irritative symptoms.  Expectations of bowel and hormonal function largely matched outcomes, with 92 percent and 86 percent, respectively, having outcomes that were the same as or better than expected.

Wittmann said that these differences may arise from the way that the pre-op counseling is given.  The research tem cautioned that the study had a low response rate.  Out of 526 patients who signed consent forms, only 152 completed all the questionnaires.  This makes it difficult to generalize the findings.  Also, while the counseling on sexual matters was standardized, the information provided by surgeons on other outcomes was not.

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Saturation Biopsy Detects More Cancers

According to a new report, analysis of 20 to 24 biopsy cores is superior to analysis of 12 to 14 cores for detecting prostate cancer in men who’ve had a normal prostate biopsy in the past.

J. Stephen Jones, M.D., from Cleveland Clinic, Ohio said, “We have shown that transrectal saturation biopsy is as easy and safe to perform as standard biopsy while detecting almost 1/3 more cancers. With these findings, we are confident that this approach offers benefit with negligible downside.”

Jones did however caution that it would be premature to suggest that this should be made universal for a number of reasons.  First, this has only been shown in one study.  Second, this must be balanced against the potential to detect clinically insignificant cancers that we might be better not knowing about even though saturation biopsy detected almost a third more cancers and had equivalence complication rates.

Jones and colleagues compared the results of extended and saturation prostate biopsy protocols in a first repeat prostate biopsy population of 1056 men (393 with a 12 to 14-core extended biopsy and 663 with a 20 to 24-core saturation biopsy.  The authors reported their findings in the Journal of Urology. The detection rate was significantly higher in the saturation biopsy group than in the extended biopsy group.  Over a third of the positive biopsies (37.8%), however, met predetermined criteria for clinical insignificance, and there was a trend toward increased detection of clinically insignificant cancer in saturation compared to extended biopsies (40.1 percent compared to 32.6 percent).

For higher-risk populations, detection rates were higher for saturation biopsy than for extended biopsy, but the differences did not reach statistical significance.  The increased detection with saturation biopsy was significant for men whose initial biopsy was completely normal.

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Prostate Cancer Vaccine Fights Tumors Without Damaging Healthy Tissue In Mice

Researchers have developed a vaccine that destroys even advanced prostate tumors without any side effects.  The vaccine has only been shown to work in mice, but the researchers from the Mayo Clinic in Rochester Minnesota and at the University of Leeds in England hope that the treatment can someday work in humans.

The researchers created a vaccine that tricks the immune system to think existing tumors are antigens by using DNA from healthy prostate cells, thus triggering its antibodies to destroy the tumors.  Eighty percent of prostate cancer cells were destroyed without harming healthy tissue in mice.

The findings were published in the peer-reviewed journal Nature Medicine.  The study’s author Richard Vile, Ph.D., professor of immunology at the Mayo Clinic said that it might take three to five years for their to be a human version of the vaccine.  More research is needed to clear some FDA hurdles.

Prostate cancer is one of the deadliest cancers.  It strikes about 220,000 men each year and kills about 32,000.  Existing conventional treatments include surgery, radiation therapy, and hormone therapy, which can damage surrounding prostate tissue.  For this reason, the researchers were pleased that the vaccine did not destroy healthy tissue in mice.

The researchers are, however, cautioning men to not get their hopes up.  Dr. Kate Holmes, research manager at England’s Prostate Cancer charity, said that even though they are hopeful that the results of this study could help to form the basis of a new cancer vaccine in the future, researchers have only studied this possibility in mice.

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Sexual Potency After Radiation Therapy for Prostate Cancer Stabilizes After Two Years

According to data from a prospective cohort study by Richard Valicenti, MD, of the University of California Davis and colleagues, sexual function declines in the first two years after external beam radiation therapy (EBRT) for prostate cancer but stabilizes thereafter.  Pretreatment sexual function was the strongest predictor of sexual function at any time after EBRT.  These findings were reported in the International Journal of Radiation Oncology.

These findings debunk the perception that sexual function declines continually after radiation therapy for prostate cancer.

Valicenti said that the results of the study allow patients and their partners to have a fuller understanding of long-term sexual side effects of EBRT and what they can expect after treatment should aid in deciding on a treatment course.

Reported rates of impotency after EBRT for prostate cancer have ranged from eight percent to 85 percent.  The authors attributed this variation to the different instruments used to assess sexual function.

Additionally, many studies included men who received androgen deprivation therapy with EBRT, possibly covering up the contributions of radiation therapy to changes in sexual function.  Many recent studies have suggested that rates of sexual dysfunction increase with follow-up, but few studies included pretreatment assessment of sexual function or conducted serial assessments of sexual function after EBRT.

The investigators prospectively followed 143 men who completed a sexual function questionnaire prior to EBRT for prostate cancer and at each follow-up visit.  The questionnaire assessed four domains of sexual function: sexual drive, erectile function, ejaculatory function, and overall satisfaction.  Scores on all four of these domains and the total score declined significantly in the first two years after EBRT compared to baseline values.  The average age of the patients was 69 year old.

During a median four years of follow-up, the patients completed 1,187 questionnaires.  Some participants were followed for as long as eight years after EBRT.  The baseline scores for sexual drive and erectile function were significantly correlated with age of patient.  Ejaculatory function was significantly correlated with age, race, and marital status.

The patients were grouped according to baseline sexual function.  The scores for the patients above and below the median sexual function value showed that differences in sexual function persisted over time.  Baseline score was the best predictor of later scores for all of the domains assessed.

There were indications that 74.1 percent of the study participants were sexually potent before EBRT.  Of these patients, 74.4 percent remained potent at one year and 70.4 percent at two years after EBRT.  There were no statistically significant changes in potency from year’s two to six.

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June 2021
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