Tuesday, November 13, 2012

Resveratrol Could Be Key to Fighting Prostate Cancer

Resveratrol, a compound found commonly in grape skins and red wine, has been shown to have several beneficial effects on human health, including cardiovascular health and stroke prevention. Now, a University of Missouri researcher has discovered that the compound can make prostate tumor cells more susceptible to radiation treatment, increasing the chances of a full recovery from all types of prostate cancer, including aggressive tumors.

"Other studies have noted that resveratrol made tumor cells more susceptible to chemotherapy, and we wanted to see if it had the same effect for radiation therapy," said Michael Nicholl, an assistant professor of surgical oncology in the MU School of Medicine. "We found that when exposed to the compound, the tumor cells were more susceptible to radiation treatment, but that the effect was greater than just treating with both compounds separately."

Prostate tumor cells contain very low levels of two proteins, perforin and granzyme B, which can function together to kill cells. However, both proteins need to be highly "expressed" to kill tumor cells. In his study, when Nicholl introduced resveratrol into the prostate tumor cells, the activity of the two proteins increased greatly. Following radiation treatment, Nicholl found that up to 97 percent of the tumor cells died, which is a much higher percentage than treatment with radiation alone.

"It is critical that both proteins, perforin and granzyme B, are present in order to kill the tumor cells, and we found that the resveratrol helped to increase their activity in prostate tumor cells," Nicholl said. "Following the resveratrol-radiation treatment, we realized that we were able to kill many more tumor cells when compared with treating the tumor with radiation alone. It's important to note that this killed all types of prostate tumor cells, including aggressive tumor cells."

Resveratrol is present in grape skins and red wine and available over-the-counter in many health food sections at grocery stores. However, the dosage needed to have an effect on tumor cells is so great that many people would experience uncomfortable side effects.

"We don't need a large dose at the site of the tumor, but the body processes this compound so efficiently that a person needs to ingest a lot of resveratrol to make sure enough of it ends up at the tumor site. Because of that challenge, we have to look at different delivery methods for this compound to be effective," Nicholl said. "It's very attractive as a therapeutic agent since it is a natural compound and something that most of us have consumed in our lifetimes."

Nicholl said that the next step would be to test the procedure in an animal model before any clinical trials can be initiated. Nicholl's studies were published in the Journal of Andrology and Cancer Science. The early-stage results of this research are promising. If additional studies, including animal studies, are successful within the next few years, MU officials will request authority from the federal government to begin human drug development (this is commonly referred to as the "investigative new drug" status). After this status has been granted, researchers may conduct human clinical trials with the hope of developing new treatments for cancer.

Wednesday, October 17, 2012

Depression increased bladder cancer mortality

As part of an ongoing, large-scale epidemiologic study of bladder cancer, Chen and colleagues collected clinical and mental health information on 464 patients with bladder cancer. They assessed patients' depression levels with the Center for Epidemiologic Studies Depression Scale (CES-D).

Depression symptoms alone affected mortality: Patients with CES-D scores of 16 or greater had a median survival time of 58 months, while those with scores below 16 had a median survival time longer than 200 months. In addition, patients with CES-D scores of 16 or greater had a 1.89-fold increased risk for all-cause mortality compared with patients with CES-D scores less than 16.

In addition, the researchers pointed to evidence that smoking cessation, weight loss and increased physical activity can potentially improve survival.

"In terms of building a prediction model for bladder cancer mortality, current models only focus on clinical variables, such as treatment and tumor stage and grade," Chen said. "Our study suggests that psychological factors and perhaps lifestyle changes could be included in this prediction model."

Monday, September 24, 2012

Like prostate cancer, bladder cancer patients may benefit from anti-androgen therapy

Bladder cancer patients whose tumors express high levels of the protein CD24 have worse prognoses than patients with lower CD24. A University of Colorado Cancer Center study published today in the Proceedings of the National Academy of Sciences shows that CD24 expression may depend on androgens – and that anti-androgen therapies like those currently used to treat prostate cancer may benefit bladder cancer patients.

MRI helps identify patients with prostate cancer who may benefit from active surveillance

In the quest to prevent prostate cancer overtreatment, "active surveillance" has emerged as a plausible option, encouraged for men whose tumors may not need immediate treatment and may never progress to more serious illness. A group of investigators from Memorial Sloan-Kettering Cancer Center report that adding endorectal magnetic resonance imaging to the initial clinical evaluation of men with clinically low prostate cancer risk helps assess eligibility for active surveillance. Their results are published in The Journal of Urology.

Saturday, August 25, 2012

Golden Age of Prostate Cancer Treatment Hailed as Fourth Drug in Two Years Extends Life

The head of one of the UK's leading cancer research organisations has hailed a golden age in prostate cancer drug discovery as for the fourth time in two years results are published finding a new drug can significantly extend life.

A study in the New England Journal of Medicine August 15 shows the drug enzalutamide can significantly extend life and improve quality of life in men with advanced prostate cancer -- in findings that could further widen the treatment options for men with the disease.

The Institute of Cancer Research, London, and its partner hospital The Royal Marsden NHS Foundation Trust jointly led the new Phase III trial of enzalutamide and the Phase III trials of two other drugs, cabazitaxel and abiraterone. Abiraterone was also discovered at The Institute of Cancer Research and was recently made available on the NHS. A further drug sipuleucel-T has also been shown to extend life in the two-year period.

Professor Alan Ashworth, chief executive of The Institute of Cancer Research (ICR), said cancer research in the UK was finally delivering new treatment options for men with advanced prostate cancer after a long period where the options were limited.

Professor Ashworth said: "Advanced prostate cancer is extremely difficult to treat, and it's taken a massive coordinated effort to finally bring new drugs into the pipeline, after decades where there were no options once old-style hormone treatment stopped working.

"What we're seeing now is an unprecedented period of success for prostate cancer research, with four new drugs shown to extend life in major clinical trials in just two years, and several others showing promise. It truly is a golden age for prostate cancer drug discovery and development."

Professor Martin Gore, medical director of The Royal Marsden Hospital, said: "We are delighted with the recent progress that has been made in the treatment of advanced prostate cancer and to see the impact this is having on our patients, many of whom are living longer with a better quality of life as the result of these new drugs."

Enzalutamide, a new type of hormone treatment, was assessed in 1,199 patients with metastatic castration-resistant prostate cancer that had previously received chemotherapy, in a multinational, randomised placebo-controlled trial sponsored by pharmaceutical companies Medivation and Astellas.

Median survival with enzalutamide was 18.4 months, compared with 13.6 months for men receiving a placebo. Around 43 per cent of men taking enzalutamide as part of the AFFIRM trial reported an improved quality of life, compared with 18 per cent of men taking a placebo. In November last year, the trial's Independent Data Monitoring Committee recommended that the trial be stopped early and men who received the placebo be offered enzalutamide.

Thursday, August 23, 2012

Prostate Cancer: Six Things Men Should Know About Tomatoes, Fish Oil, Vitamin Supplements, Testosterone, PSA Tests

When it comes to prostate cancer, there's a lot of confusion about how to prevent it, find it early and the best way -- or even whether -- to treat it. Below are six common prostate cancer myths along with research-based information from scientists at Fred Hutchinson Cancer Research Center to help men separate fact from fiction.

Myth 1 -- Eating tomato-based products such as ketchup and red pasta sauce prevents prostate cancer. "The vast majority of studies show no association," said Alan Kristal, Dr.Ph., associate director of the Hutchinson Center's Cancer Prevention Program and a national expert in prostate cancer prevention. Kristal and colleagues last year published results of the largest study to date that aimed to determine whether foods that contain lycopene -- the nutrient that puts the red in tomatoes -- actually protect against prostate cancer.

After examining blood levels of lycopene in nearly 3,500 men nationwide they found no association. "Scientists and the public should understand that early studies supporting an association of dietary lycopene with reduced prostate cancer risk have not been replicated in studies using serum biomarkers of lycopene intake," the authors reported in Cancer Epidemiology, Biomarkers & Prevention. "Recommendations of professional societies to the public should be modified to reflect the likelihood that increasing lycopene intake will not affect prostate cancer risk."

Myth 2 -- High testosterone levels increase the risk of prostate cancer. "This is a lovely hypothesis based on a very simplistic understanding of testosterone metabolism and its effect on prostate cancer. It is simply wrong," Kristal said. Unlike estrogen and breast cancer, where there is a very strong relationship, testosterone levels have no association with prostate cancer risk, he said. A study published in 2008 in the Journal of the National Cancer Institute, which combined data from 18 large studies, found no association between blood testosterone concentration and prostate cancer risk, and more recent studies have confirmed this conclusion.

Myth 3 -- Fish oil (omega-3 fatty acids) decrease prostate cancer risk. "This sounds reasonable, based on an association of inflammation with prostate cancer and the anti-inflammatory effects of omega-3 fatty acids," Kristal said. However, two large, well-designed studies -- including one led by Kristal that was published last year in the American Journal of Epidemiology -- have shown that high blood levels of omega-3 fatty acids increase the odds of developing high-risk prostate cancer.

Analyzing data from a nationwide study of nearly 3,500 men, they found that those with the highest blood percentages of docosahexaenoic acid, or DHA, an inflammation-lowering omega-3 fatty acid commonly found in fatty fish, have two-and-a-half times the risk of developing aggressive, high-grade prostate cancer compared to men with the lowest DHA levels. "This very sobering finding suggests that our understanding of the effects of omega-3 fatty acids is incomplete," Kristal said.

Myth 4 -- Dietary supplements can prevent prostate cancer. Several large, randomized trials that have looked at the impact of dietary supplements on the risk of various cancers, including prostate, have shown either no effect or, much more troubling, they have shown significantly increased risk. "The more we look at the effects of taking supplements, the more hazardous they appear when it comes to cancer risk," Kristal said. For example, the Selenium and Vitamin E Cancer Prevention Trial (SELECT), the largest prostate cancer prevention study to date, was stopped early because it found neither selenium nor vitamin E supplements alone or combined reduced the risk of prostate cancer. A SELECT follow-up study published last year in JAMA found that vitamin E actually increased the risk of prostate cancer among healthy men. The Hutchinson Center oversaw statistical analysis for the study, which involved nearly 35,000 men in the U.S., Canada and Puerto Rico.

Myth 5 -- We don't know which prostate cancers detected by PSA (prostate-specific antigen) screening need to be treated and which ones can be left alone. "Actually, we have a very good sense of which cancers have a very low risk of progression and which ones are highly likely to spread if left untreated," said biostatistician Ruth Etzioni, Ph.D., a member of the Hutchinson Center's Public Health Sciences Division.

In addition to blood levels of PSA, indicators of aggressive disease include tumor volume (the number of biopsy samples that contain cancer) and Gleason score (predicting the aggressiveness of cancer by how the biopsy samples look under a microscope). Gleason scores range from 2-5 (low risk) and 6-7 (medium risk) to 8-10 (high risk).

"Men with a low PSA level, a biopsy Gleason score of 6 or lower and very few biopsy samples with cancer are generally considered to be very low risk," Etzioni said. Such newly diagnosed men increasingly are being offered active surveillance -- a watchful waiting approach -- rather than therapy for their disease, particularly if they are older or have a short life expectancy.

"The chance that these men will die of their disease if they are not treated is very low, around 3 percent," she said. Similarly, such men who opt for treatment have a mortality rate of about 2 percent. "For the majority of newly diagnosed cases of prostate cancer, giving initial clinical and biopsy information, we can get a very good idea of who should be treated and who is likely to benefit from deferring treatment."

Myth 6 -- Only one in 50 men diagnosed with PSA screening benefits from treatment. "This number, which was released as a preliminary result from the European Randomized Study of Prostate Cancer Screening, is simply incorrect," Etzioni said. "It suggests a very unfavorable harm-benefit ratio for PSA screening. It implies that for every man whose life is saved by PSA screening, almost 50 are overdiagnosed and overtreated."

"Overdiagnosis" is diagnosing a disease that will never cause symptoms or death in the patient's lifetime. "Overtreatment" is treating a disease that will never progress to become symptomatic or life-threatening.

The 50-to-one ratio is based on short-term follow-up and "grossly underestimates" the lives likely to be saved by screening over the long term and overestimates the number who are overdiagnosed. "The correct ratio of men diagnosed with PSA testing who are overdiagnosed and overtreated versus men whose lives are saved by treatment long term is more likely to be 10 to one," she said.

Friday, August 10, 2012

Calcium, Vitamin D Supplements May Pose Risks for Men With Prostate Cancer

Although they're standard treatment for men with prostate cancer who are taking hormonal therapy, calcium and vitamin D supplements may do more harm than good, according to a new study.

Men who undergo hormone-depletion therapy for prostate cancer are at risk for osteoporosis, but the supplements do not prevent this bone loss and may actually boost patients' odds for heart disease and aggressive prostate cancer, research from Wake Forest Baptist Medical Center suggests.

"Calcium and/or vitamin D supplementation to prevent loss of bone mineral density in these men seems so logical that no one had questioned whether it works," study co-author, Mridul Datta, a postdoctoral fellow at Wake Forest Baptist, explained in a hospital news release.

"It wouldn't be so bad if there simply was no obvious benefit," added the study's lead author, Gary Schwartz, a prostate cancer epidemiologist at Wake Forest Baptist. "The problem is that there is evidence that calcium supplements increase the risk of cardiovascular disease and aggressive prostate cancer, the very disease that we are trying to treat."

In the study, the researchers reviewed guidelines for calcium and vitamin D supplements as well as the results of 12 clinical trials of these supplements involving almost 2,400 men with prostate cancer. All of the men were receiving hormone-deprivation therapy. The researchers also examined the men's bone mineral density before and after treatment.

According to the study, the men undergoing hormone therapy for prostate cancer who took the recommended daily doses of calcium and vitamin D supplements lost bone density.

The researchers also pointed out that increased dietary calcium is associated with a greater risk for aggressive prostate cancer and heart disease.

"The wake-up call of these findings," concluded Datta, "is that the presumption of benefit from calcium and vitamin D supplements that have been routinely recommended to these men must be rigorously evaluated."

The study's authors said more research is needed to confirm their findings and investigate the possible risks of calcium and vitamin D supplementation, particularly heart disease and prostate cancer.

One expert agreed that more study is needed.

The study authors "say that traditional approaches use too little calcium and/or vitamin D, but that as one increases the doses there are other risks, such as cardiovascular events," noted Dr. Louis Potters, a prostate cancer specialist and chair of radiation medicine at North Shore - LIJ Health System, in New Hyde Park, N.Y. "So that the trade-off for treating osteoporosis is associated with other risks."

Potters stressed that "not all men with prostate cancer need hormone therapy, only those with high-risk or advanced disease. And for those men, they need to have a discussion with their physician about the risks of these medications and how best to perhaps mitigate some of those risks."

The study was published online in the July issue of The Oncologist.

Monday, June 11, 2012

New therapy extends life for prostate cancer patients

Study of a new drug treatment represents a new protocol for those with advanced prostate cancer that has spread to bone

Prostate cancer patients with advanced tumors that have spread to bone have a poor chance of surviving. Patients with the disease may now live longer with a new line of radioisotope therapy, say researchers at the Society of Nuclear Medicine's 2012 Annual Meeting.

The skeletal systemis the number one metastatic site in patients with prostate cancer. Bone metastases occur when the primary cancer is transmitted through the blood and develops in the bone.This is a phase III study for the radioisotope therapy Radium-223 chloride, or Ra-223, which seeks out bone metastases with very potent alpha particles that are deadly to tumors. The powerful drug has a short range of penetration of alpha particles, sparing nearby healthy tissues and essential bone marrow. It is initially being studied for the treatment of castration-resistant prostate cancer, a late-stage form of cancer that is typically characterized by extensive skeletal metastases that are resistant to treatment.

"This is a pivotal study of a new treatment that potentially offers a better standard of care for patients with advanced prostate cancer," says Val Lewington, professor of clinical therapeutic nuclear medicine at King's College and Guy's and St Thomas' Hospital in London, United Kingdom. "Radium-223 offers a completely new approach to the treatment of bone metastases. It systemically treats multiple sites of disease simultaneously and is usually very well tolerated. Serious side effects are unusual, and the risk of bone marrow suppression is low even in patients who have been heavily pretreated with chemotherapy."

According to the U.S. National Cancer Institute, 241,740 new cases of prostate cancer are expected to be diagnosed and 28,170 to die from the disease this year in the United States. In the past 25 years, many bone targeted drugs have been developed to treat the disease, but they have more of a palliative effect, treating pain, but not necessarily prolonging the lives of patients.

Men with castration-resistant prostate cancer generally live three to five years after diagnosis. This double-blind and randomized study was able to show that of the 921 patients treated with either Ra-223 or a placebo, patients who received the drug lived an average of three months longer. Therapy was administered in six injections at four-week intervals. In addition to prolonged survival, those treated with Ra-223 also experienced delayed onset of complications due to bone metastases. Therapy monitoring is made possible with molecular imaging techniques called scintigraphy and positron emission tomography, which provide information about biological processes, including those involved in cancerous tumors.

An expanded access program is already underway in the United States and a similar program is expected to open in Europe in 2012. Further clinical trials are also being considered. Formal regulatory approval will be sought in mid-2012 in both the United States and Europe.

Monday, June 4, 2012

Intermittent Hormone Therapy for Prostate Cancer Inferior to Continuous Therapy

Many men with metastatic, hormone-sensitive prostate cancer live longer on continuous androgen-deprivation therapy (also known as hormone therapy) than on intermittent therapy, according to a seventeen-year study led by SWOG, a cancer research cooperative group funded by the National Cancer Institute (NCI).

Men with newly diagnosed metastatic prostate cancer are usually either surgically castrated or given medications to suppress the production of male hormones that drive their cancer. The treatment can help keep the disease at bay temporarily, but in the majority of patients the cancer will relapse and contribute to the patient’s death.

Surgical castration is permanent but “medical castration” provides men the potential advantage of receiving therapy intermittently. A halt in this therapy is followed in time by a rise in testosterone levels. Scientific data suggested that intermittent treatment may delay the cancer relapse, and that the rise in testosterone may result in an improvement in the patient’s quality of life.

These data provided the rationale for the phase III clinical trial SWOG-9346, the largest such study to date in men with metastatic, hormone-sensitive disease. Results of this study demonstrate that intermittent androgen-deprivation (AD) therapy is not as good as continuous hormone therapy with regard to patient longevity.

The findings are to be presented today at the plenary session of the American Society for Clinical Oncology’s (ASCO’s) annual meeting by the study’s principal investigator, Maha Hussain, M.D., F.A.C.P., of the University of Michigan Comprehensive Cancer Center.

“Based on these results,” Hussain says, “we can conclude that intermittent AD is not as effective as continuous AD in men with metastatic prostate cancer.”

Clinical researchers from the SWOG network, with funding from the NCI, led an international team in conducting the study at more than 500 sites, enrolling 3,040 men with hormone-sensitive, metastatic prostate cancer between 1995 and 2008.

All men got an initial course of androgen-deprivation treatment for seven months. The 1,535 eligible men whose prostate-specific antigen (PSA) level dropped to 4 ng/mL or less by the end of those seven months were then assigned at random to stop therapy (the intermittent therapy group) or continue therapy (the continuous therapy group).

Those randomized to the intermittent therapy arm had their treatment suspended until their PSA rose to a predetermined level, at which time they started another seven-month course of androgen-deprivation therapy, cycling on and off therapy in this way as long as their PSA levels continued to respond appropriately during the “on” cycle.

Men on continuous therapy had a median overall survival time of 5.8 years from the time of randomization, with 29 percent of these men surviving at least 10 years. Those on intermittent therapy had a median overall survival time of 5.1 years, with 23 percent surviving at least 10 years from the time they were randomly assigned to a treatment arm.

The researchers found, in additional analyses, that men with “minimal disease” (disease that had not spread beyond the lymph nodes or the bones of the spine or pelvis) did significantly better on continuous therapy, while men with “extensive disease” (disease that had spread beyond the spine, pelvis, and lymph nodes or to the lungs or liver) seemed to do about as well using either treatment approach.

Additional analyses indicated that the median overall survival time for those with minimal disease was 7.1 years on continuous androgen-deprivation therapy compared to only 5.2 years on intermittent treatment. Patients with extensive disease had median overall survival times of 4.4 years on continuous therapy and 5.0 years on intermittent therapy.

“In the past when it came to using hormone therapy in this disease, doctors viewed the disease as one entity and adopted a ‘one size fits all’ approach,” Hussain says. “Based on this study’s findings, it seems that one size does not necessarily fit all.”

Trial researchers also compared quality-of-life measures across the two study arms during the first 15 months following patient randomization, including measures of sexual function (impotence and libido), physical and emotional function, and energy level. They found improved sexual function in men who received intermittent therapy as compared to those on continuous therapy. A second presentation at an ASCO Poster Discussion session (morning of June 4th, Poster #25) reports on these preliminary quality-of-life findings from SWOG-9346 (Abstract #4571, CM Moinpour, DL Berry, et al).

“Though we see potential quality-of-life benefits with IAD,” Hussain says, “from a medical perspective, the primary findings of the study demonstrating that IAD is inferior with regard to overall survival should be the primary consideration in counseling all patients who are interested in intermittent therapy and particularly those with minimal disease.”

In brief: 1,535 men with metastatic, hormone-sensitive prostate cancer were randomized to intermittent androgen-deprivation (AD) therapy or continuous AD therapy after seven months of androgen deprivation._• When overall survival times were compared, intermittent AD was inferior to continuous AD._• For the subset of patients with minimal disease, continuous AD was superior to intermittent AD._• For patients with extensive disease, overall survival was comparable between intermittent and continuous AD._• A number of quality-of-life measures got higher scores in the intermittent AD arm than the continuous AD arm.

Prostate cancer statistics: More than 240,000 men in the United States will be diagnosed with prostate cancer in 2012, according to the American Cancer Society, and more than 28,000 will die of the disease.

Tuesday, May 22, 2012

PSA Screening Benefits Few, Harms Many, Says Panel

A US government-sponsored panel of independent experts that reviews evidence and develops recommendations for preventive clinical services says the harms of PSA-based testing for prostate cancer outweigh the benefits. The recommendation has provoked a strong and angry response from many patient and medical groups.

In a report published early online before print in the 21 May of Annals of Internal Medicine, the US Preventive Services Task Force (USPSTF) writes of PSA-based screening for prostate cancer: "[it] may benefit a small number of men but will result in harm to many others".

The USPSTF is a group of primary care physicians and epidemiologists that is appointed and funded by the US Department of Health and Human Services' Agency for Healthcare Research and Quality (AHRQ). Its recommendations are important because they influence how health policy is shaped and what insurers do. For instance, it is empowered by the Affordable Care Act to decide which screenings Americans receive.

This recommendation is the task force's "final word" on PSA-based testing. It follows a period of public comment after its last published recommendation in 2008, when at the time it concluded there was no evidence to support PSA testing for men over 75.

The task force says it has since then reviewed the evidence published since 2008 and concluded that the harms of PSA-based testing outweigh the benefits, regardless of age. The task force does not take costs into account when developing recommendations: it just weighs health benefits against harms.

The task force posted a draft of this final recommendation for public comment in October 2011. At the time it gave PSA-based screening a "D" grade, which means doctors should not offer the test to their patients because there are more harms than benefits.

Many who commented at the time suggested the "D" be changed to a "C" which says doctors could offer the test to patients who ask for it. But the panel has not changed its draft recommendation, and has stuck to the "D" grade.

According to its Annals of Internal Medicine report, the task force considered two major trials that assessed the life-saving benefits of PSA-based testing in asymptomatic men.

The first trial took place in the US. It did not show that PSA-screening reduce deaths to prostate cancer. The second trial took place in seven European countries and found PSA screening reduced deaths by one death per 1,000 men screened in a subgroup aged 5 to 69 years, mostly in two countries. The other five countries did not find a statistically significant reduction deaths.

The task force reports there is strong evidence that PSA-based screening can be harmful.

Just under 90% of men whose prostate cancer is detected via PSA undergo early treatment, either with surgery, radiation, or androgen deprivation therapy, they write. They say the evidence shows up to 5 out of every 1,000 men die within 1 month of surgery, and between 10 and 70 that survive have to live the rest of their lives with urinary incontinence, erectile and bowel dysfunction.

Monday, May 21, 2012

Statins may slow prostate growth

Statins drugs prescribed to treat high cholesterol may also work to slow prostate growth in men who have elevated PSA levels, according to an analysis led by researchers at Duke University Medical Center.

The finding, presented at the annual meeting of the American Urological Association, provides additional insight into the effects of cholesterol-lowing drugs such as statins on the prostate. Previous studies at Duke and elsewhere had found a link between statins and lower levels of PSA, a protein produced by the prostate that is often elevated by cancer or by non-lethal prostatic diseases.

In the current finding, prostatic growth rate diminished among men with elevated PSA levels who took statins, although that effect was relatively small and tapered off after about two years.

"Given that prostate enlargement is an important health problem in the United States and elsewhere, and will be a larger problem as the population ages, it's important to understand and treat its causes," said Roberto Muller, M.D., a urology fellow at Duke and lead author of the study.

Enlarged prostate, most commonly diagnosed as benign prostate hyperplasia, causes urinary problems that can escalate to bladder and kidney damage. Up to 90 percent of men over the age of 70 have some symptoms associated with enlarged prostate, according to the National Institutes of Health.

Muller and colleagues used data gathered for an unrelated, large trial originally testing whether a drug called dutasteride could help reduce the risk of prostate cancer. To test their hypothesis that statins may be associated with slower prostate growth, the researchers culled the data of more than 6,000 men, including 1,032 who also took statins.

Men on statins tended to be older than non-users, and thus were expected to have greater prostate sizes. But prostate sizes were actually similar between statin users and non-users at the start of the study. That finding provided the first suggestion that statins might affect prostate growth.

When changes in prostate growth were compared two years after the start of the trial, men in the study who took a statin drug had less prostate growth, regardless of whether they had been randomly assigned to take dutasteride or a dummy pill. Prostate growth was an average 5 percent less in men who took both a statin and dutasteride pill compared to men who took only dutasteride. For those taking a statin and a dummy pill, prostate growth was 3.9 percent less than for men taking only the placebo.

Those reductions, however, did not persist after two years.

"We don't yet understand the mechanisms that might be causing this," Muller said. "Some have suggested that statins may have anti-inflammatory properties, and inflammation has been linked to prostate growth, but this needs further study."

Muller said the findings in the current research also suggest that lifestyle choices such diet and exercise may not only affect cholesterol, but also prostate health.

"Prostate enlargement was once considered an inexorable consequence of aging and genetics, but there is growing awareness that prostate growth can be influenced by modifiable risk factors," Muller said. "In this context, the role of blood cholesterol levels and cholesterol-lowering drugs such as statins warrants further study."

Vitamin D + TB Vaccine: Allies in Fight Against Bladder Cancer?

The tuberculosis vaccine is often used as a treatment for bladder cancer, and adding vitamin D might improve the vaccine’s effectiveness, according to new research from the University of Rochester Medical Center presented today at the American Urological Association annual meeting.

Yi-Fen Lee, Ph.D., associate professor of Urology at URMC, has conducted a pre-clinical study in a mouse model showing that a combination of vitamin D therapy and the Bacillus Calmette-Guerin (BCG) vaccine greatly improves bladder cancer survival. The next phase, an early clinical trial in patients, will begin soon as part of a collaborative research project between the URMC’sJames P. Wilmot Cancer Center and the Roswell Park Cancer Institute in Buffalo.

The connection between vitamin D and tuberculosis was established long ago, when ancient societies sent people with TB into the sunlight for therapy. Increasing vitamin D levels is known to wake up cells and trigger an immune response whenever infection or inflammation is present.

Also well established is the use of the TB vaccine to treat several forms of bladder cancer. The vaccine works by pushing the body’s immune system to fight the cancer cells. However, approximately 30 to 40 percent of people with bladder cancer who receive the vaccine do not respond to it.

Lee is investigating whether a lack of vitamin D in these patients might explain the poor response.

Prior studies have shown that BCG, the modified bacteria that causes TB, turns on a toll-like receptor signal that makes more vitamin D receptors and induces a key enzyme that converts to the most potent, bioactive form of vitamin D, or 1,25-hydroxylvitamin D3. So Lee thought it was likely that boosting the levels of vitamin D in the body would activate this process, enhancing the vaccine.

The mouse study involved four arms: a control group, a group that received vitamin D treatment alone, a group that received BCG treatment alone, and a fourth group that received the combination of vitamin D and the BCG vaccine. The latter (combination therapy) group was the only group in which 100 percent survived bladder cancer, Lee said.

“Vitamin D appears to be critical to the success of BCG immunotherapy,” Lee said, although she does not advise taking high doses of vitamin D unless under medical supervision. “Just as importantly, though, we have shown the migration and signaling involved in establishing vitamin D as a biomarker that can be easily measured.”

Monday, May 7, 2012

Oral Vitamin D Supplements Fight Prostate Cancer

Higher oral doses of plain vitamin D raised levels of calcitriol in prostate tissue. Higher prostate levels of calcitriol, a hormone made from vitamin D, corresponded with lower levels of the proliferation marker Ki67 and increased levels of cancer growth-inhibitory microRNAs in prostate cancer cells.

The results not only point to the mechanisms by which vitamin D affects the rate of prostate cancer growth, but also indicate that vitamin D may slow the growth of prostate cancer cells — a key finding given that the role of vitamin D in prostate cancer has been “controversial, with some suggesting that higher levels of vitamin D should be avoided,” said Reinhold Vieth, Ph.D., professor at the University of Toronto in Toronto, Ontario, Canada.

“This study shows calcitriol makes the foot come off the gas pedal of cancer growth. We are not able to prove that the speed of the car has slowed down, but it certainly is a good sign,” said Vieth. “We expect that this early-phase clinical trial will open the door for more detailed clinical research into the usefulness of vitamin D in the treatment or prevention of prostate cancer.”

Vieth and colleagues previously reported that in men who were being monitored regularly for prostate cancer, higher vitamin D levels slowed the rate of rise in prostate-specific antigen levels. They randomly assigned 66 men scheduled for radical prostatectomy to daily vitamin D in doses of 400, 10,000 or 40,000 IU for three to eight weeks before surgery. Researchers found that calcitriol levels in the prostate increased progressively with each daily dose of vitamin D, with 40,000 IU showing the highest levels. These higher levels of calcitriol corresponded with lower prostate levels of Ki67, a protein that indicates prostate cancer cell growth, as well as higher levels of specific growth-inhibitory microRNAs.

Vieth stressed that he and his colleagues do not advocate vitamin D supplementation in doses higher than 4,000 IU daily. Patients were assigned to the 40,000 IU daily dose because of the short presurgical time frame available for study, not as a regular regimen.

“Plain vitamin D provides the raw material to permit the body to take care of its own needs,” he said. “We showed here that plain vitamin D allows the prostate to regulate its own level of calcitriol, and at the doses we used, for the time frame we used, it has been safe with the hoped-for desirable outcomes.”

The next step in this line of research will be to conduct a phase III clinical trial in which men who are being monitored for prostate cancer progression will be randomly assigned to placebo or to a “high” dose of plain vitamin D.

Wednesday, April 25, 2012

Robot Assisted Prostate Cancer Surgery Compares Favorably

Outcomes from use of a robot to assist surgeons in removal of a cancerous prostate are at least as good, if not better, than the other two techniques used for a radical prostatectomy -- open or laparoscopic surgery -- according to a large meta analysis led by researchers at NewYork-Presbyterian/Weill Cornell.

The study, published February 24 online in European Urology, should help resolve some of the controversy regarding use of the robotic option, known as robot assisted laparoscopic radical prostatectomy (RALP), says the study's lead author, Dr. Ashutosh Tewari, director of the Lefrak Center for Robotic Surgery and director of the Prostate Cancer Institute at New York-Presbyterian Hospital/Weill Cornell Medical Center.

"There is a lot of debate about the best way to remove a cancerous prostate gland," says Dr. Tewari, who is also the Ronald P. Lynch Professor of Urologic Oncology and professor of urology and public health at Weill Cornell Medical College. "Since the robotic technology is expensive, the patient benefits often get intertwined with the societal costs. It is clear, however, that robotic surgery is the most popular surgical modality today. This study represents the largest ever systematic review of patient outcomes comparing robotic-assisted, laparoscopic and open radical prostatectomy.

By analyzing 400 original research articles -- all that have been published to date on the three methods -- Dr. Tewari and his colleagues concluded that RALP is more effective than a pure laparoscopic approach and comparable to an open surgical approach in completely removing cancer from the body. Positive surgical margins, a measure of oncological efficacy, were lower in patients receiving robotic radical prostatectomy as compared to those undergoing laparoscopic prostatectomy.

The researchers also found that robot assisted surgery had fewer intraoperative and perioperative complication rates when compared to both laparoscopic and open approaches. In addition, robotic showed both less intraoperative blood loss and less blood transfusions as compared to open surgery.

The meta analysis included treatment information on 286,876 patients, representing the largest compilation of radical prostatectomy patients to date.

"Understanding the best method to remove the prostate matters," Dr. Tewari says, "because prostate cancer is the most common diagnosed cancer and the second most common cause of cancer death for men in developed countries."

But given the nature of the study, Dr. Tewari says he cannot recommend one surgical approach over another. He emphasizes that surgical approaches need to be adjusted for the technique and experience of the surgeon. Many studies have shown that surgical experience is an independent predictor for outcomes, far beyond the approach alone.

"This paper is innovative in its attempt to unpack the outcomes data, in a systematic way, surrounding the three surgical modalities for prostate cancer treatment, but the data we used were not standardized -- outcome measures differed between studies," he says. "Still I believe the results are meaningful in that it shows RALP has at least as good outcomes as the other methods."

Challenges of Randomized Studies for Prostate Surgery

The three forms of surgery studied are "open radical" in which the prostate is removed via an abdominal incision in the belly button or pubic bone; laparoscopic prostatectomy that requires several small minimally invasive "keyhole" incisions in the abdomen, and robotic surgery, which is a form of laparoscopic surgery. RALP is done through keyholes with the aid of robotic arms that eliminate hand tremor as well as advanced optics that magnify the prostate and surrounding nerves in three-dimensions.

"It is hard to accrue patients for randomized studies. We have an ongoing study open at our institution, investigating the quality of life differences between robotic and open radical prostatectomy. This is designed as a randomized controlled study," he says. "But no one has enrolled because they did not want to be randomized to a treatment they don't prefer. Patients often come, especially to prostate cancer specialists, self-selecting for a particular treatment modality."

So Dr. Tewari and Peter Wiklund, M.D., of Sweden's Karolinska University Hospital, developed a study that examined all of the peer-reviewed studies published on any of the three techniques.

This ambitious effort was aimed at understanding the short-term (30 day) outcomes of the three surgical techniques. Given the short time frame, the meta analysis did not compare outcomes for urinary continence or sexual potency.

The researchers determined that complications and mortality were low for all three methods, suggesting that radical prostatectomy is a safe procedure.

Significant differences found were in the lower positive surgical margin (PSM) rates for RALP compared with laparoscopic surgery and lower intra operative and perioperative complications for RALP in comparison to other modalities. "PSM rates are important because they represent the effectiveness by which cancer is removed," Dr. Tewari says. "The RALP PSM rate was as good as open surgery," he adds.

The researchers also found that both laparoscopic and robotic surgery patients experienced lower rates of blood loss and transfusions and a shorter hospital stay compared with patients who had traditional surgery. Other measures, such as rates of readmission, reoperation, and complications, seemed to favor RALP, the researchers say.

"We would love to be able to directly compare the three prostatectomy surgical techniques, but that may not happen," Dr. Tewari says. "This study is the first to provide an important -- and much needed -- analysis of the short term benefits and risks between curative surgeries that many men rely on."

Oregano Kills Prostate Cancer Cells

Oregano, the common pizza and pasta seasoning herb, has long been known to possess a variety of beneficial health effects, but a new study by researchers at Long Island University (LIU) indicates that an ingredient of this spice could potentially be used to treat prostate cancer, the second leading cause of cancer death in American men.

Prostate cancer is a type of cancer that starts in the prostate gland and usually occurs in older men. Recent data shows that about 1 in 36 men will die of prostate cancer. Estimated new cases and deaths from this disease condition in the US in 2012 alone are 241,740 and 28,170, respectively. Current treatment options for patients include surgery, radiation therapy, hormone therapy, chemotherapy, and immune therapy. Unfortunately, these are associated with considerable complications and/or severe side effects.

Dr. Supriya Bavadekar, PhD, RPh, Assistant Professor of Pharmacology at LIU's Arnold & Marie Schwartz College of Pharmacy and Health Sciences, is currently testing carvacrol, a constituent of oregano, on prostate cancer cells. The results of her study demonstrate that the compound induces apoptosis in these cells. Apoptosis, Dr. Bavadekar explains, is programmed cell death, or simply "cell suicide." Dr. Bavadekar and her group are presently trying to determine the signaling pathways that the compound employs to bring about cancer cell suicide.

"We know that oregano possesses anti-bacterial as well as anti-inflammatory properties, but its effects on cancer cells really elevate the spice to the level of a super-spice like turmeric," said Dr. Bavadekar. Though the study is at its preliminary stage, she believes that the initial data indicates a huge potential in terms of carvacrol's use as an anti-cancer agent. "A significant advantage is that oregano is commonly used in food and has a 'Generally Recognized As Safe' status in the US. We expect this to translate into a decreased risk of severe toxic effects."

"Some researchers have previously shown that eating pizza may cut down cancer risk. This effect has been mostly attributed to lycopene, a substance found in tomato sauce, but we now feel that even the oregano seasoning may play a role," stated Dr. Bavadekar. "If the study continues to yield positive results, this super-spice may represent a very promising therapy for patients with prostate cancer."

Tuesday, April 17, 2012

Kidney cancer patients do better when whole kidney is not removed

Surgery to remove only the tumor preferable to removing entire kidney

Kidney cancer patients who had only their tumor removed had better survival than patients who had their entire kidney removed, according to a new study from researchers at the University of Michigan Comprehensive Cancer Center.

After an average of five years, 25 percent of patients who had a so-called partial nephrectomy, in which only the tumor and a small margin of healthy tissue is removed, had died, while 42 percent of patients who had radical nephrectomy, in which the entire kidney is removed, had died, the study found. Results appear in the April 18 Journal of the American Medical Association.

"For patients who are candidates for partial nephrectomy, it should be the preferred treatment option. We found that patients who were younger or had pre-existing medical conditions benefited most from partial nephrectomy," said lead study author Hung-Jui Tan, M.D., a urology resident at the U-M Medical School.

The researchers looked at 7,138 Medicare beneficiaries with early stage kidney cancer up to eight years after treatment. Patients were equally likely to die of kidney cancer, regardless of the type of surgery they received, suggesting that each procedure was equally likely to cure the cancer. The survival discrepancy was found in the number of patients who died from any cause.

The study showed that if only seven patients chose partial nephrectomy over radical nephrectomy, it would save one extra life.

Early stage kidney cancers have become more common recently. These are often discovered by chance when patients receive an X-ray or CT scan for something unrelated.

"As more and more people are identified with these small, early stage cancers, there's more interest in understanding how best to treat these patients," says senior study author David C. Miller, M.D., M.P.H., assistant professor of urology at the U-M Medical School and member of U-M's Institute for Health Care Policy and Innovation.

The question, though, is whether partial nephrectomy – which is a more technically challenging procedure and potentially associated with more short-term complications – is preferable to radical nephrectomy. Removing a kidney can increase the risk of chronic kidney disease, which is associated with lipid disorders, cardiovascular disease and renal failure.

The debate is similar to breast cancer surgery, in which studies have found that lumpectomy plus radiation is comparable to mastectomy. While that choice often comes down to a cosmetic trade-off, the trade-off with kidney cancer is a potential higher risk of short-term complications with partial nephrectomy vs. avoiding chronic kidney disease in the long term.

"This study does not suggest every patient with early stage kidney cancer should get a partial nephrectomy. It supports the notion that we need to expand the use of partial nephrectomy and make it a preferred treatment choice for patients with small tumors as much as possible, to optimize long term survival," Miller says.

Intensity Modulated Radiation Therapy optimal for localized prostate cancer

A treatment for localized prostate cancer known as Intensity Modulated Radiation Therapy (IMRT) is better than conventional conformal radiation therapy (CRT) for reducing certain side effects and preventing cancer recurrence, according to a study published in the April 18, 2012 issue of the Journal of the American Medical Association. In 2012, approximately 241,740 American men will be diagnosed with prostate cancer.

The study also showed IMRT to be as effective as proton therapy, a newer technique that has grown in popularity in recent years.

Ronald Chen, MD, MPH, senior author, says, "Patients and doctors are often drawn to new treatments, but there have not been many studies that directly compare new radiation therapy options to older ones."

Chen is assistant professor of radiation oncology and a research fellow at the Sheps Center for Health Services Research at the University of North Carolina at Chapel Hill. He is a member of UNC Lineberger Comprehensive Cancer Center.

He explains, "In the past 10 years, IMRT has largely replaced conventional CRT as the main radiation technique for prostate cancer, without much data to support it. This study validated our change in practice, showing that IMRT better controls prostate cancer and results in fewer side effects.

"Our data show that in comparing IMRT to proton therapy, IMRT patients had a lower rate of gastrointestinal side effects, but there were no significant differences in rates of other side effects or additional therapies."

Study scientists report that compared to CRT, IMRT was associated with fewer diagnoses of gastrointestinal (GI) symptoms, such as rectal bleeding or diarrhea, hip fractures and additional cancer therapy, but more difficulty with sexual function. Proton therapy was associated with more GI problems than IMRT.

The UNC team used Surveillance, Epidemiology, and End Results (SEER)-Medicare linked data from 2000-2009 for approximately 13,000 patients with non-metastatic prostate cancer. SEER is composed of 16 population-based cancer registries representing approximately 26 percent of the US population.

This study is an example of comparative effectiveness research, which seeks to inform health care decisions by providing new research-based evidence about the benefits and harms of different health care interventions.

Tim Carey, MD, director of the Sheps Center at UNC, said, "This type of research is critical, comparing one type of treatment with alternatives, so that patients and their providers can arrive at the best decisions for each individual."

CRT, IMRT and Proton therapy represent three types of radiation, each attempting to deliver radiation treatment to a tumor while minimizing radiation dose to surrounding organs. Use of proton therapy use in prostate cancer is controversial because of its high cost and unproven benefit compared to other standard forms of radiation like IMRT.

Adverse effects among different radiation therapies for prostate cancer

In an analysis of three different types of radiation therapy used to treat localized prostate cancer, compared with conformal radiation therapy, intensity-modulated radiation therapy (IMRT) was associated with fewer diagnoses of gastrointestinal adverse effects, hip fractures, and receipt of additional cancer treatments but more erectile dysfunction, while proton therapy was associated with more gastrointestinal adverse effects than IMRT, according to a study in the April 18 issue of JAMA, a theme issue on comparative effectiveness research.

Ronald C. Chen, M.D., M.P.H., of the University of North Carolina at Chapel Hill, presented the findings of the study at a JAMA media briefing at the National Press Club.

"Prostate cancer is the most common malignancy in men, with more than 200,000 diagnoses and 30,000 deaths per year. Recent advances in technology have led to costlier treatments such as minimally invasive radical prostatectomy, intensity-modulated radiation therapy, and proton therapy. The adoption of these technologies resulted in a $350 million increase in health care expenditures in 2005 alone," according to background information in the article. Various organizations have called for comparative effectiveness research of localized prostate cancer treatments. "The clinical benefit from these newer treatments is unproven, and comparative effectiveness research examining different radiation techniques is lacking," the authors write.

Dr. Chen and colleagues conducted a study to examine the comparative adverse effects and disease control outcomes after different radiation techniques in a recent cohort of prostate cancer patients. Specifically, the researchers compared IMRT, which has been rapidly adopted and is currently the most commonly used technique, with the older conformal radiation therapy; and compared proton therapy, the use of which also has increased, with IMRT. The population-based study used Surveillance, Epidemiology, and End Results-Medicare-linked data from 2000 through 2009 for patients with localized prostate cancer. The primary outcomes measured were rates of gastrointestinal adverse effects (such as rectal bleeding or diarrhea) and urinary adverse effects, erectile dysfunction, hip fractures, and receipt of additional cancer therapy – as an indicator for disease recurrence.

The use of IMRT vs. conformal radiation therapy increased from 0.15 percent in 2000 to 95.9 percent in 2008. In the propensity-score adjusted analysis (n = 12,976), the researchers found that men treated with IMRT were less likely to receive a diagnosis of gastrointestinal adverse effects and hip fracture but more likely to receive a diagnosis of erectile dysfunction. Also, IMRT patients were nearly 20 percent less likely to receive additional cancer therapy.

In a propensity score-matched comparison between IMRT and proton therapy (n = 1,368), IMRT patients had a 34 percent lower risk of gastrointestinal adverse effects. There were no significant differences in rates of other adverse effects or additional therapies between IMRT and proton therapy.

"Proton therapy is a high-profile, high-cost prostate cancer treatment. Since 2007, multiple proton facilities have been built, and direct-to-consumer advertising is likely to lead to a substantial increase in use," the authors write. "Overall, our results do not clearly demonstrate a clinical benefit to support the recent increase in proton therapy use for prostate cancer."

The researchers add that the findings that patients receiving IMRT were less likely than those receiving conformal radiation therapy to undergo additional cancer treatments is consistent with the use of IMRT to deliver dose-escalated treatment, resulting in improved cancer control, as demonstrated by randomized trials. "Taken together, these results suggest that IMRT facilitated radiation dose escalation without compromising acceptable long-term morbidity."

"Comparative effectiveness research in localized prostate cancer treatments is needed because of the large number of men with this disease and the continued trend of a rapid increase in use of newer and costlier treatments with unproven clinical benefit," the authors write.

Friday, February 17, 2012

Botanical Formula Effective In Treating Prostate Cancer


A study published online in The International Journal of Oncology reports findings from a team of scientists at Indiana University, Methodist Research Institute, who examined a botanical formula containing botanical extracts, phytonutrients, botanically-enhanced medicinal mushrooms, and antioxidants, that kills aggressive prostate cancer tumors.

The researchers conducted experiments in mice using a human prostate cancer tumor model. This is the third publication from a major university study reporting important findings of this particular multi-nutrient prostate formula to fight the invasive behavior of aggressive prostate cancer cells, tumor growth and metastasis.

Dr. Daniel Sliva, who led the research, commented:

"Multiple studies demonstrate that this prostate formula is a possible treatment for hormone refractory (androgen independent) prostate cancer."

The findings of the study demonstrate that the prostate formula substantially inhibited tumor growth in aggressive, hormone refractory, androgen independent human-prostate cancer cells. After evaluating the formula's potential toxicity, it was deemed safe, with no signs of toxicity at the highest dosages.

Dr. Isaac Eliaz, researcher and formulator, declares:

"This study is a milestone in the research of this formula, demonstrating its safety and effectiveness in treating human prostate cancer in an animal model. These positive results offer a significant contribution to the field of prostate cancer research, and add to the growing body of published data substantiating the role of natural compounds in the treatment of prostate cancer."

The study, which used a xenograft tumor model of human prostate cancer in mice, revealed that in comparison to controls, oral administration of the formula achieved a statistically important suppression of 27% in tumor growth.

What proved even more significant was that the formula suppressed the expression of several genes that affect cancer proliferation and metastasis, three of which, IGF2, NRNF2 and PLAU/uPA are connected to potentially producing metastasis, other than controlling aggressive prostate cancer growth. The formula was also observed to substantially increase the expression of CDKN1A, a gene that fights prostate cancer by specifically inhibiting other cancer promoting cellular mechanisms.

The formula's abilities to suppress specific genes that are associated with aggressive prostate cancer growth and proliferation, and increase the expression of cancer-fighting genes, proves that this integrative formula has multiple anti-cancer mechanisms and genetic targets. The pre-clinical in vivo study supports earlier published in vitro data, which also demonstrate the formula's ability of decreasing expression of PLAU/uPA genes in aggressive, hormone-independent prostate cancer cells.

Dr. Sliva concludes:

"In summary, this dietary supplement is a natural compound for the possible therapy of human hormone refractory (independent) prostate cancer."

The formula's ongoing research in prostate cancer models continue to demonstrate promising results, with further studies coming up.

Thursday, February 16, 2012

Four new drugs will change prostate cancer care, Colorado expert says


Four new drugs could transform prostate cancer from terminal to chronic disease
Not just chemo — new, targeted drugs act in novel and interesting ways
These drugs mark first major advances in prostate cancer care in nearly 15 years
After a decade and a half of near stagnation, four new drugs could help make advanced prostate cancer a chronic illness instead of a terminal disease, a leading Colorado prostate cancer expert says.

“It’s not just chemotherapy. The drugs have different and innovative methods of action. One is a bone protective agent; another’s a more effective hormone agent; another is radiotherapy; and the final one is the first drug tested for cancer immunotherapy,” says E. David Crawford, MD, investigator at the University of Colorado Cancer Center and head of urologic oncology at University of Colorado Hospital.

“Even without the addition of any more drugs, we may now have the tools that in combination will allow us to extend the survival prognosis of a prostate cancer patient long enough to make prostate cancer a disease a patient is more likely to die with than from,” Crawford says.

Along with Thomas Flaig, MD, Crawford describes these advances in prostate cancer treatment in a recent review for the journal Oncology.

First is the drug Denosumab, which Crawford says, “has three uses in protecting the bones of prostate cancer patients.” It can prevent bone fractures in patients with existing bone metastasis; it can prevent osteoporosis in patients whose calcium is depleted as a side-effect of hormone therapy; and (pending FDA approval) it has been shown to hold off the occurrence of bone metastasis for an average of four months in patients whose spiking PSA scores predict the likely onset of bone involvement.

Second is the drug Alpharadin, which is one of a novel and exciting class of “radiopharmaceuticals” – drugs that emit radiation and allow doctors to precisely deliver radiation to tumor sites. In the case of Alpharadin, it emits alpha rather than beta particles, which allows more precise tumor targeting of bone metastasis sites with less collateral damage to surrounding bone marrow.

Third, the drug Prostvac is the first “immunotherapy” drug used for the treatment of cancer. The drug acts like a vaccine, priming the immune system to recognize and thus fight against prostate cancer cells. In a phase II clinical trial of 125 patients, the drug extended the median survival time from 16.6 to 25.1 months.

Finally, the drug Abiraterone Acetate completely suppresses the body’s ability to make testosterone, which many prostate cancers need to grow (as opposed to previous drugs, which hoped to out-compete testosterone with estrogen, or imperfectly controlled testosterone production).

Crawford notes that these drugs are being approved for use only after more established therapies have failed and hopes that in coming years science may accelerate the use of these drugs to first-line therapies.

“Before we just had hormone therapy, then we got chemo, and each therapy we added packed on another couple months of survival. Now with these news drugs we’re tacking on even more time. The light at the end of the tunnel is the hope that we’ll turn this into a chronic disease and now we might have the tools that in some combination will do it,” Crawford says.

* To learn more about these and other cutting-edge strategies to combat advanced prostate cancer, refer for Crawford and Flaig’s recent review, Optimizing Outcomes of Advanced Prostate Cancer: Drug Sequencing and Novel Therapeutic Approaches.


Thursday, February 2, 2012

A New Screening Method for Prostate Cancer: PSA Velocity Risk Count Testing


A new study by NYU Langone Medical Center and Northwestern University Feinberg School of Medicine shows novel PSA velocity (PSAV) risk count testing may provide a more effective way for physicians to screen men for clinically significant prostate cancer. The new study, published online by the British Journal of Urology International on February 1, 2012, shows the benefits of tracking a man’s PSA levels over time to help doctors more accurately assess his risk of life-threatening prostate cancer.

“Risk count could represent a new way to screen for prostate cancer by focusing on men with the greatest risk of harmful prostate cancers,” said lead author Stacy Loeb, MD, an urologist in the Department of Urology and the Joel E. Smilow Comprehensive Prostate Cancer Center at NYU Langone. “The goal of risk count is to help identify the aggressive, clinically significant prostate cancers before advanced symptoms develop, while decreasing the diagnosis of insignificant cancers.”

Prostate cancer is the second leading cause of cancer death in American men, with an estimated 1 in 6 men diagnosed with the disease during their lifetime. Prostate cancer does not present symptoms until advanced stages so screening for the disease is vital. Currently, a PSA blood test is the standard screening method to evaluate a man’s risk of prostate cancer. It measures the amount of prostate-specific antigen in the blood, a substance made only in the prostate gland. An elevated PSA can indicate the presence of disease. However, PSA can also be elevated with benign prostate enlargement and one high PSA value does not always mean an aggressive prostate cancer is present.

The new PSAV risk count screening works by monitoring fluctuations in PSA levels over time to analyze a man’s risk of prostate cancer, instead of relying on just one PSA test result to assign prostate cancer risk. The risk count is calculated by counting the number of times in a row that the PSA level in the blood increases by 0.4 ng/mL. If PSA goes up by more than 0.4 units multiple years in a row, the risk count rises indicating the patient has an increased risk of aggressive prostate cancer. For example, a man who has a PSA screening for two years in a row would be given a “2” risk count if his serial PSA velocity measurements increased by more than 0.4 units, a “1” risk count if there was only one increase by more than 0.4 units, and a “0” risk count if there was no increase by more than 0.4 units.

In the study, researchers showed PSAV risk count could improve the specificity of screening for prostate cancer and advanced stages of the disease. Researchers evaluated 18, 214 men undergoing prostate cancer screening, 1,125 of which were diagnosed with the disease. The study results show sustained rises in PSA levels over time indicate a significantly greater risk of prostate cancer and more aggressive disease. In the study, a risk count of “2” was associated with a greater than 8-times risk of prostate cancer and a 5-fold greater risk of aggressive disease.

The authors conclude risk count screening may be useful in diagnosing aggressive prostate cancer earlier while possibly reducing unnecessary biopsy, as well as the overdiagnosis and resulting overtreatment of low-risk prostate cancer.

“A persistently rising PSA is a harbinger for life-threatening prostate cancer,” said the study’s senior author, William Catalona, MD, professor of Urology at Northwestern University. “Our study findings show looking at how much PSA changes over time helps distinguish which cancers are aggressive more so than a single PSA value.”

In an accompanying editorial, Dr. H. Ballentine Carter from the Brady Urological Institute at Johns Hopkins who initially suggested the concept of looking at PSA changes over time, affirms that in order to determine the likelihood of aggressive prostate cancer, “you want to know your patient’s risk count, not just their age and PSA level.”

Occasional binge drinking not harmful


No effect on heart disease and mortality among moderate drinkers

Most studies have found that binge drinking is associated with a loss of alcohol's protective effect against ischemic heart disease (IHD) and most studies have found an increase of coronary risk among binge drinkers.

This study followed 26,786 men and women who participated in the Danish National Cohort Study in 1994, 2000, and 2005 and sought to see if binge drinking increased the risk of IHD or all-cause mortality among "light-to-moderate" drinkers: (up to 21 drinks/week for men and up to 14 drinks/week for women). A "drink" was 12g.

"Binge drinking" (more that 5 drinks on an occasion) did not show differences in risk of ischemic heart disease (coronary disease) or total mortality than among always moderate drinkers. These results are somewhat different from results of many other epidemiologic studies that have shown increased risk of health problems (even higher risk of coronary disease) to be associated with what was referred to as "binge drinking."

Why there were no adverse effects of binge drinking in this study has provoked considerable discussion among members of the Forum. The assessments of alcohol were based on consumption in the week prior to the examination, so data was not available to judge whether or not binge-drinking episodes occurred rarely or regularly. Data was available for smoking, education, physical activity, BMI, and self-reported hypertension and diabetes. There was a strong increase in IHD risk and mortality from binge drinking among heavy drinkers, but the authors were comparing outcomes in binge vs. non-binge drinkers among subjects in the "light-to-moderate" categories, and so in all comparisons, the relative risk of IHD and all-cause mortality was higher for non-drinkers than for all other categories of drinkers.

The general consensus of opinion among Forum members is the definition of "binge drinking." The rapid consumption of more than 5 drinks on an empty stomach surely has different effects than the consumption of alcohol over several hours with food, such as during a prolonged dinner. The rate of consumption strongly affects the consequences of alcohol; the speed of drinking and context should constitute part of the definition of 'bingeing' and not just the total number of drinks.

The Forum concludes that "binge drinking," however defined, is not a healthy pattern of alcohol consumption. But the circumstances of consumption (rate of consumption, with or without food, etc.) may also be important in its definition and in judging its effects on health.

The Forum does not take the results of this single study to support binge drinking. What the Danish results suggest is that the occasional "excess" embedded in a moderate consumption pattern is not shown to be harmful in this study. As recognized in responsible drinking guidelines from Australia, Canada and the US, occasional episodes of consumption greater than the recommended daily levels do not necessarily change the classification of a normally moderate drinker into that of an abuser.

Investigational urine test can predict high-risk prostate cancer in men who chose 'watchful waiting'

SEATTLE – Initial results of a multicenter study coordinated by researchers at Fred Hutchinson Cancer Research Center indicates that two investigational urine-based biomarkers are associated with prostate cancers that are likely to be aggressive and potentially life-threatening among men who take a "watchful waiting," or active-surveillance approach to manage their disease. Ultimately, these markers may lead to the development of a urine test that could complement prostate biopsy for predicting disease aggressiveness and progression.

Study principal investigator Daniel Lin, M.D., an associate member of the Hutchinson Center's Public Health Sciences Division, will present these findings today at the 2012 Genitourinary Cancers Symposium of the American Society of Clinical Oncology in San Francisco.

"Prostate biopsies are invasive and don't always pick up all of the cancer. Post-digital-rectal exam urine collection is much less invasive. If a urine-based diagnostic test could be developed that could help predict aggressive disease or disease progression, that would be ideal," said Lin, who is also an associate professor and chief of urologic oncology at the University of Washington Department of Urology.

Lin leads a nationwide consortium of eight institutions called the Canary Prostate Active Surveillance Study, an endeavor dedicated to identifying and validating biomarkers of high-risk prostate cancer.

Because many prostate cancers are slow growing and never become life threatening, many men with early stage prostate cancer choose active surveillance – delaying treatment while closely monitoring to see whether the cancer progresses.

Two urine-based biomarkers were found to correlate with indicators of aggressive disease: tumor volume (the number of biopsy samples that contain cancer) and Gleason score (predicting the aggressiveness of cancer by how it looks under a microscope). The markers that mirrored these correlates of disease aggressiveness were:

PCA3 – a non-coding RNA that is found at high levels in prostate cancer relative to benign prostate cells; and
TMPRSS2-ERG – the fusion of TMPRSS2, a gene that is regulated by androgens, with ERG, an oncogene. These genetic rearrangements are found in about half of all prostate cancers and are thought to play a role in prostate cancer development.
The findings were based on an interim analysis of data collected from 401 men who opted for active surveillance of their cancer. The study compared biomarker performance to clinical data collected at the time of study entry. Ultimately, the study aims to enroll 1,000 men and follow them for at least five years.

"The ultimate goal is that men on active surveillance could use a test based on these biomarkers or others to complement biopsy and PSA data to indicate or rule out the presence of an undetected aggressive cancer or future development of aggressive cancer," said Lin, who cautioned that these initial results, while promising, need to be confirmed in a larger study that would evaluate changes in these urine biomarkers over time, along with correlation to disease progression during active surveillance. Lin further noted that neither PCA3 nor TMPRSS2-ERG are FDA-approved for prostate cancer detection and that their use in active surveillance is investigational.

Saturday, January 28, 2012

Brachytherapy May Be An Effective Option For High-Risk Prostate Cancers


Brachytherapy for high-risk prostate cancers patients has historically been considered a less effective modality, but a new study from radiation oncologists at the Kimmel Cancer Center at Jefferson suggests otherwise. A population-based analysis looking at almost 13,000 cases revealed that men who received brachytherapy alone or in combination with external beam radiation therapy (EBRT) had significantly reduced mortality rates.

Their findings are reported online in the International Journal of Radiation Oncology,Biology,Physics.

Brachytherapy involves the precise placement of radiation sources directly at the site of a tumor and is typically used to treat low and intermediate risk prostate cancers. However, brachytherapy treatment for high-risk patients is less common and controversial, given in part to early retrospective studies that found it to be associated with lower cure rates compared to EBRT.

Many experts believe that these early series were limited by poor brachytherapy technique, and that high-quality contemporary brachytherapy may be an effective tool against high-risk prostate cancer.

"The study contradicts traditional policies of using brachytherapy in just low and intermediate risk patients by suggesting there may instead be an improvement in prostate cancer survival for high-risk patients," said co-author Timothy Showalter, M.D., assistant professor in the Department of Radiation Oncology at Thomas Jefferson University Hospital, and associate research member of Jefferson's Kimmel Cancer Center. "Although studies like this cannot prove an advantage for brachytherapy, our report does suggest that brachytherapy is no less effective than EBRT and should be considered for some men with high-risk prostate cancer."

Researchers identified 12,745 Surveillance, Epidemiology and End Results database patients diagnosed from 1988 to 2002 with high-grade prostate cancer of poorly differentiated grade and treated with brachytherapy (7.1 percent), EBRT alone (73.5 percent) or brachytherapy plus EBRT (19.1 percent). The team used multivariate models to examine patient and tumor characteristics associated with the likelihood of treatment with each radiation modality and the effect of radiation modality on prostate cancer-specific mortality.

Treatment with brachytherapy alone or brachytherapy in combination with EBRT, the researchers found, was associated with significant reduction in prostate cancer-specific mortality rates compared to EBRT alone.

Significant predictors of use of brachytherapy or brachytherapy plus EBRT were younger age, later year of diagnosis, urban residence and earlier T-stage.

According to the researchers, including lead author Xinglei Shen, M.D., a resident in Jefferson's Department of Radiation Oncology and a part-time master's degree student in the Jefferson School of Population Health, the study's findings provide ample evidence to further study brachytherapy as part of an effective treatment strategy for men with high-grade prostate cancer.

"Today, for the most part, brachytherapy is not being used for these high-risk patients or even recommended," Dr. Shen said. "But if you look at the biology and theory behind it, it makes sense: you can really give a lot more dose with brachytherapy than with EBRT alone to the prostate. And this presents an opportunity for high-risk patients."

Tuesday, January 24, 2012

Prostate Cancer Study Proves Drug Delays Disease Progression


For men diagnosed with low-risk, localized prostate cancer, being treated with the drug dutasteride (“Avodart”) delays disease progression and initiating active treatment, and also reduces anxiety, show the results of a three-year international clinical trial led by Dr. Neil Fleshner, Head of the Division of Urology, University Health Network (UHN).

The findings are published online today in The Lancet. “The results prove that using active surveillance plus dutasteride is a viable, safe and effective treatment option for men who often undergo aggressive local treatment despite low risk of dying from the disease,” says Dr. Fleshner, a surgical oncologist in UHN’s Princess Margaret Cancer Program and Professor of Surgery at the University of Toronto. Dr. Fleshner also holds the Love Chair in Prostate Cancer Prevention Research.

“This is very good news for men with low-risk disease because aggressive treatment can have a major impact on their quality of life, with risks of impotence and incontinence,” says Dr. Fleshner.

The three-year clinical trial enrolled 302 men between the ages of 48 and 82 diagnosed with low-risk localized prostate cancer and regularly monitored for clinical changes – a treatment option called “active surveillance”. In the trial – known as REDEEM (REduction by Dutasteride of clinical progression Events in Expectant Management of prostate cancer) – participants were randomized 1:1 to receive dutasteride or a matching placebo daily. The men also underwent biopsies at 1.5 and three years.

The study showed a significant delay in disease progression in the men treated with dutasteride – 38% compared with 48% who received the placebo. As well, the final biopsies showed the men treated with the drug were less likely to have cancer detected – 36% compared with 23%.

“This is the first study to show that a 5a-reductase inhibitor such as dutasteride reduces the need for aggressive treatment in low-risk disease,” says Dr. Fleshner. “The drug, currently commonly used to treat enlarged prostate, works by inhibiting the male sex hormone that causes the enlargement in the first place.”

Dr. Fleshner says a small percentage of men reported drug-related side effects including sexual difficulty with either desire or erections (5%), or breast tenderness or enlargement (3%). “It’s important to realize that these drugs have been around for almost 20 years in clinical practice to treat enlarged prostates and so we have a wealth of knowledge about their side effects, which are reversible if the drug is stopped.”

Participants were also assessed for cancer-related anxiety and the men on dutasteride reported feeling much less anxious because their biopsies and PSA values improved, adds Dr. Fleshner. (PSA – or prostate-specific antigen – is a blood test used to help diagnose prostate cancer.)

Tuesday, January 10, 2012

Cutting-edge gene therapy for bladder cancer


Bladder cancer, most frequently caused by smoking and exposure to carcinogens in the workplace, is one of the top 10 most common forms of cancer in men and women in the U.S. More than 70 percent of bladder cancers are diagnosed in stage T1 or less and have not invaded the muscle layer. At these early stages, standard treatment is surgery (transurethral resection) and the burning away of tumors with high energy electricity (fulguration). Many patients also may receive subsequent intravesical chemotherapy because there is often a high-risk for cancer recurrence.

The prognosis for recurrent cancer is poor, which drives clinician-scientists like William Larchian, MD, Urologic Oncologist, University Hospitals Urology Institute at University Hospitals Case Medical Center, and Associate Professor of Surgery, Case Western Reserve University School of Medicine, and his colleagues to develop an immunotherapy for bladder cancer that will stimulate the body's own natural defense mechanisms to cure the disease and prevent recurrence.

"What is interesting is that our bodies are capable of identifying, responding to and killing tumor cells naturally," explained Dr. Larchian. "We are developing a vaccination system to enhance this response and drive an effective immune response against existing and future bladder tumor cells in patients diagnosed with bladder cancer."

IL-2, a cytokine-signaling molecule, stimulates the T-cell immune response to cancer cells in the bladder. Dr. Larchian and his colleagues have developed a system that reliably introduces multiple copies of IL-2 DNA into bladder cancer cells.

"This method allows for more gene copies to enter the cells," he said, "and we are able to see higher rates of transfection compared to retroviral methods."

The enhanced IL-2 protein expression has been shown to successfully stimulate T-cell response and eliminate bladder tumors in a mouse model, particularly when followed by transfection with B7.1 gene. The addition of the B7.1 gene, which encodes an immune co-stimulatory molecule, enhanced T-cell production logarithmically and produced a 70 percent cure rate. Rechallenge with new cancer cells was also prevented. Clinical translation of this research has been submitted for Institutional Review Board approval at UH Case Medical Center.

Other research by Dr. Larchian and his colleagues aims to leverage this work to develop a gene-therapy system that can be utilized to deliver other key defense genes.

"Our future pursuits," he said, "will include using this system with very specific biological response modifiers, including anti-angiogenesis factors, and with the tumor suppressor gene, MCP3." Dr. Larchian also is developing a targeted drug delivery system using nanoparticles for bladder cancer treatment.

Thursday, January 5, 2012

Proton therapy effective prostate cancer treatment

Proton therapy, a type of external beam radiation therapy, is a safe and effective treatment for prostate cancer, according to two new studies published in the January issue of the International Journal of Radiation Oncology•Biology•Physics (Red Journal), the American Society for Radiation Oncology's (ASTRO) official scientific journal.

In the first study, researchers at the University of Florida in Jacksonville, Fla., prospectively studied 211 men with low-, intermediate-, and high-risk prostate cancer. The men were treated with proton therapy, a specialized type of external beam radiation therapy that uses protons instead of X-rays. After a two year follow-up, the research team led by Nancy Mendenhall, MD, of the University of Florida Proton Therapy Institute, reported that the treatment was effective and that the gastrointestinal and genitourinary side effects were generally minimal.

"This study is important because it will help set normal tissue guidelines in future trials," Dr. Mendenhall, said.

In the second study, researchers from Massachusetts General Hospital in Boston, Loma Linda University Medical Center in Loma Linda, Calif., and the Radiation Therapy Oncology Group in Philadelphia performed a case-matched analysis comparing high-dose external beam radiation therapy using a combination of photons (X-rays) and protons with brachytherapy (radioactive seed implants).

Over three years, 196 patients received the external beam treatments. Their data was compared to 203 men of similar stages who received brachytherapy over the same time period. Researchers then compared the biochemical failure rates (a statistical measure of whether the cancer relapses) and determined that men who received the proton/photon therapy had the same rate of recurrence as the men who received brachytherapy.

"For men with prostate cancer, brachytherapy and external beam radiation therapy using photons and protons are both highly effective treatments with similar relapse rates," John J. Coen, MD, a radiation oncologist at Massachusetts General Hospital in Boston, said. "Based on this data, it is our belief that men with prostate cancer can reasonably choose either treatment for localized prostate cancer based on their own concerns about quality of life without fearing they are compromising their chance for a cure."