TUESDAY, Oct. 9 (HealthDay News) -- Prostate cancer patients receiving androgen-deprivation therapy, a common form of hormone treatment proven to slow tumor growth and prolong life, may face a nearly threefold higher risk of dying from heart disease, a new study suggests.
The apparent danger results from a drop in testosterone levels that is central to androgen-deprivation therapy's (ADT) effectiveness at curbing prostate cancer, the study authors said.
This drop in testosterone can provoke insulin resistance, leading to type 2 diabetes, as well as a gain in body mass, body fat and so-called bad cholesterol. Collectively, this group of problems is called the "metabolic syndrome," a condition long-associated with cardiac complications.
"However, I think overall ADT does help people with prostate cancer, and until it's studied further this can't be considered proof that there's a connection between the cardiac effects and hormone therapy," said study author Dr. Henry K. Tsai, who throughout the study period served as a resident in training in the Harvard Radiation Oncology Program in Boston.
"But patients need to think about being evaluated carefully by their doctor to see whether they're appropriate candidates for hormone therapy and be informed about the potential risks," Tsai added.
This new finding, published in the Oct. 17 issue of the Journal of the National Cancer Institute, follows research released in 2005 that highlighted ADT's link to an increased risk for bone fractures and osteoporosis.
The new findings are based on an analysis of medical records and questionnaires completed by nearly 4,900 patients between the ages of 39 and 86 who had been diagnosed with localized prostate cancer between 1995 and 2004.
All the patients had participated in a larger nationwide prostate cancer research project involving more than 13,000 men, during which all had indicated whether they had any preexisting medical complications in addition to cancer.
Of the 4,900 patients, nearly 3,300 had undergone prostate removal surgery following diagnosis.
The remainder underwent nonsurgical treatments, such as external beam radiation therapy; brachytherapy (involving the insertion of small radioactive pellets directly into the prostate); and/or cryotherapy (involving the freezing of tumor cells).
In addition, 266 of those patients who underwent surgery and 749 of those receiving an alternate treatment also received androgen-deprivation therapy.
The patients were tracked for an average of about four years following the start of all treatments; the patients receiving ADT did so for an average of about four months.
Tsai and his colleagues found that patients over the age of 65 who had undergone both prostate removal surgery and ADT had a 5.5 percent increased risk of dying from a cardiac event within five years of starting the hormone treatment. This compared to a 2 percent greater risk among patients older than 65 who had surgery alone.
The "relative risk" jump was similar among younger patients. Those under 65 who had surgery and hormone therapy had a 3.6 percent greater risk of death from heart disease within five years, compared with a 1.2 percent risk among those undergoing surgery alone.
ADT was not associated with any increased cardiac risk among patients undergoing any of the nonsurgical treatments.
An editorial accompanying the study calls for more research into the topic.
Jerome Seidenfeld and his colleagues at the University of Connecticut Health Center suggest that while Tsai's analysis of previously collected data raises an "interesting hypothesis," no definitive link to cancer risk can be proved until a clinical trial of prostate cancer patients currently undergoing hormone treatment is launched.
Tsai agreed.
"I pretty much feel similarly," Tsai said. "The editorial emphasizes that this is a preliminary study, and clinical trials are the gold standard. And we need one to confirm our findings."
Tsai, currently working as a radiation oncologist with Radiation Oncology Consultants in Princeton, N.J., said he doesn't want prostate cancer patients to view androgen-deprivation therapy with alarm.
"I don't think patients should be afraid," he said. "This is just what I'd call emerging data, and while the relative increase in risk for heart disease is large, in absolute terms the risk is still very small."
Dr. Nelson Neal Stone, a clinical professor of urology and radiation oncology at Mount Sinai School of Medicine in New York City, said the exact mechanism by which ADT might boost the risk for cardiac complications remains undefined, despite a widespread appreciation for the array of problems that accompany the metabolic syndrome.
In that light, he suggested that physicians should target the onset of the life-threatening syndrome as well as the life-prolonging treatment.
"The message is that we need to start paying attention to our patients' general health when we put them on hormonal therapy," he said. "And perhaps we should be putting them on a diet to control for the potential side effects of the therapy, and the serious impact it can have on their health."
"We can't take away the hormones altogether because there's a major benefit to that treatment," Stone added. "But we need to develop a good strategy for dealing with the negative consequences that occur."
Saturday, October 27, 2007
MONDAY, Sept. 24 (HealthDay News) -- Prostate cancer prevention studies conducted since the 1990s are poised to revolutionize the field in the next five years, a Canadian analysis concludes.
"I am optimistic that for the coming generation, beginning with men in their 20s and 30s, we will have a viable strategy to decrease the chance of developing prostate cancer later in life," said study lead author Dr. Neil Fleshner.
A professor of surgery, Fleshner heads the division of urology at Princess Margaret Hospital, part of the University Health Network at the University of Toronto.
His team's overview of the last 15 years of prostate cancer prevention research is published in the Nov. 1 issue of Cancer.
According to the U.S. National Cancer Institute (NCI), cancer of the prostate is the most common non-skin cancer among American men. Most patients diagnosed with the disease do not ultimately die of it. However, because of its high prevalence, prostate cancer remains the third biggest cancer killer for men in the Western world.
By age 40, one-third of men have already developed small carcinomas of the prostate, the researchers noted. By age 60, that figure rises to 60 percent, and, in North America, one in seven men will develop prostate cancer at some point in their lives.
But the disease is also often slow-moving, sometimes taking decades to develop from a single prostate cancer cell to advanced-stage illness.
That fact has led to the hope that doctors could intervene in ways that could halt disease progression at an early stage.
One such study reviewed by Fleshner and his colleagues was the Prostate Cancer Prevention Trial (PCPT), overseen by the NCI.
In this instance, NCI researchers looked at the ability of finasteride -- a so-called 5-alpha reductase inhibitor (5ARI) medication -- to impede the growth-promoting impact of hormones such as testosterone on prostate cancer.
Designed to interfere with the body's ability to uptake testosterone and other male hormones, finasteride was offered to half the almost 19,000 men over the age of 55 who participated in the seven-year study.
At the study's start, all the men screened as "normal" following digital rectal exams. As well, all had registered low-scoring prostate-specific antigen (PSA) levels. An elevated level of PSA in the blood is an indication of prostate cancer.
Yearly digital rectal exams and PSA screenings revealed that almost 25 percent of the men on placebo went on to develop prostate cancer. However, just a little over 18 percent of those taking finasteride got the disease.
Fleshner and his associates noted, however, that most of the cancer cases prevented appeared to be of the early stage, low-grade variety. More serious, higher-grade disease actually appeared to become more common among patients taking finasteride. This raises concern that the medication might actually hasten disease progression, the Canadian group cautioned.
Nevertheless, their review concluded that finasteride might, in the near future, become an effective prevention tool for men with a strong family history of the disease.
Additional studies are currently under way to explore the benefits of newer hormone manipulation drugs, they noted, including the 5ARI drug dutasteride and the selective estrogen receptor modifier toremifene. Results should be available in a few years.
Meanwhile, the Canadian team also uncovered evidence suggesting that limiting fat in the diet might also reduce prostate cancer risk. Various studies have highlighted unhealthful connections between fat and pesticide exposure, testosterone level increases, and the rise of oxidative stress -- all of which seem to contribute to prostate disease risk.
By contrast, evidence has mounted that increasing vitamin E and selenium intake could also protect against prostate cancer, they said. Recent research also suggests that consuming more green tea, soy, vitamin D, and lycopene (typically found in tomatoes) might confer similar benefits.
Fleshner and his colleagues hailed the new emphasis on prevention. The arrival of even more helpful prevention information might be just around the corner, they said.
"What's exciting now is that there's no doubt any longer that prostate disease is preventable," said Fleshner. "This will not necessarily translate into improved mortality rates, because it may be that we will be able to prevent more low-grade disease than high-grade."
But many men with low-grade disease currently undergo surgery and other treatments that can impact their quality of life, he noted. "So, even if we are able to reduce just the need for unnecessary treatment, this will be a good step," Fleshner said.
Not everyone shares that optimism, however.
Dr. Nelson Neal Stone, a clinical professor of urology and radiation oncology at the Mount Sinai School of Medicine in New York City, believes that when it comes to preventing prostate cancer, "we're still sort of at a loss."
"Today, you can't really advise a patient to do anything to prevent prostate cancer," he said. "The best study so far -- the PCPT study-- did show a 25 percent drop in prostate cancer, but that was in low-grade tumors, whereas the incidence of high-grade tumors may actually have gone up. And a lot of the dietary factors that showed promise --vitamins, selenium -- have come into question as to whether they're really helping patients."
"So, I would agree that in five year's time, we will probably come up with strategies to reduce the clinical incidence of the disease in terms of detecting low-grade cancer," he added. "But that doesn't have much meaning in a patient's life. What has meaning is the ability to prevent a high-grade tumor from metastasizing and potentially ending a patient's life. And nobody has shown that anything can reduce that."
"In my opinion, the best strategy we have now is early detection," Stone said. "If you find a patient with an aggressive prostate cancer, and it's small and in the prostate and you find it early, you save that patient's life."
"I am optimistic that for the coming generation, beginning with men in their 20s and 30s, we will have a viable strategy to decrease the chance of developing prostate cancer later in life," said study lead author Dr. Neil Fleshner.
A professor of surgery, Fleshner heads the division of urology at Princess Margaret Hospital, part of the University Health Network at the University of Toronto.
His team's overview of the last 15 years of prostate cancer prevention research is published in the Nov. 1 issue of Cancer.
According to the U.S. National Cancer Institute (NCI), cancer of the prostate is the most common non-skin cancer among American men. Most patients diagnosed with the disease do not ultimately die of it. However, because of its high prevalence, prostate cancer remains the third biggest cancer killer for men in the Western world.
By age 40, one-third of men have already developed small carcinomas of the prostate, the researchers noted. By age 60, that figure rises to 60 percent, and, in North America, one in seven men will develop prostate cancer at some point in their lives.
But the disease is also often slow-moving, sometimes taking decades to develop from a single prostate cancer cell to advanced-stage illness.
That fact has led to the hope that doctors could intervene in ways that could halt disease progression at an early stage.
One such study reviewed by Fleshner and his colleagues was the Prostate Cancer Prevention Trial (PCPT), overseen by the NCI.
In this instance, NCI researchers looked at the ability of finasteride -- a so-called 5-alpha reductase inhibitor (5ARI) medication -- to impede the growth-promoting impact of hormones such as testosterone on prostate cancer.
Designed to interfere with the body's ability to uptake testosterone and other male hormones, finasteride was offered to half the almost 19,000 men over the age of 55 who participated in the seven-year study.
At the study's start, all the men screened as "normal" following digital rectal exams. As well, all had registered low-scoring prostate-specific antigen (PSA) levels. An elevated level of PSA in the blood is an indication of prostate cancer.
Yearly digital rectal exams and PSA screenings revealed that almost 25 percent of the men on placebo went on to develop prostate cancer. However, just a little over 18 percent of those taking finasteride got the disease.
Fleshner and his associates noted, however, that most of the cancer cases prevented appeared to be of the early stage, low-grade variety. More serious, higher-grade disease actually appeared to become more common among patients taking finasteride. This raises concern that the medication might actually hasten disease progression, the Canadian group cautioned.
Nevertheless, their review concluded that finasteride might, in the near future, become an effective prevention tool for men with a strong family history of the disease.
Additional studies are currently under way to explore the benefits of newer hormone manipulation drugs, they noted, including the 5ARI drug dutasteride and the selective estrogen receptor modifier toremifene. Results should be available in a few years.
Meanwhile, the Canadian team also uncovered evidence suggesting that limiting fat in the diet might also reduce prostate cancer risk. Various studies have highlighted unhealthful connections between fat and pesticide exposure, testosterone level increases, and the rise of oxidative stress -- all of which seem to contribute to prostate disease risk.
By contrast, evidence has mounted that increasing vitamin E and selenium intake could also protect against prostate cancer, they said. Recent research also suggests that consuming more green tea, soy, vitamin D, and lycopene (typically found in tomatoes) might confer similar benefits.
Fleshner and his colleagues hailed the new emphasis on prevention. The arrival of even more helpful prevention information might be just around the corner, they said.
"What's exciting now is that there's no doubt any longer that prostate disease is preventable," said Fleshner. "This will not necessarily translate into improved mortality rates, because it may be that we will be able to prevent more low-grade disease than high-grade."
But many men with low-grade disease currently undergo surgery and other treatments that can impact their quality of life, he noted. "So, even if we are able to reduce just the need for unnecessary treatment, this will be a good step," Fleshner said.
Not everyone shares that optimism, however.
Dr. Nelson Neal Stone, a clinical professor of urology and radiation oncology at the Mount Sinai School of Medicine in New York City, believes that when it comes to preventing prostate cancer, "we're still sort of at a loss."
"Today, you can't really advise a patient to do anything to prevent prostate cancer," he said. "The best study so far -- the PCPT study-- did show a 25 percent drop in prostate cancer, but that was in low-grade tumors, whereas the incidence of high-grade tumors may actually have gone up. And a lot of the dietary factors that showed promise --vitamins, selenium -- have come into question as to whether they're really helping patients."
"So, I would agree that in five year's time, we will probably come up with strategies to reduce the clinical incidence of the disease in terms of detecting low-grade cancer," he added. "But that doesn't have much meaning in a patient's life. What has meaning is the ability to prevent a high-grade tumor from metastasizing and potentially ending a patient's life. And nobody has shown that anything can reduce that."
"In my opinion, the best strategy we have now is early detection," Stone said. "If you find a patient with an aggressive prostate cancer, and it's small and in the prostate and you find it early, you save that patient's life."
FRIDAY, Sept. 14 (HealthDay News) -- Men who've been adding vitamin E or the tomato nutrient lycopene to their diets to cut their risk of prostate cancer may need to think again.
According to a new study, neither carotenoids (such as lycopene), retinol, nor tocopherols (forms of vitamin E) appear to reduce the odds of prostate malignancy -- findings that are in line with two other recent publications.
"Our overall findings are null," said lead researcher Timothy Key, deputy director of the Cancer Research UK Epidemiology Unit at the University of Oxford, U.K.
"This large study does not support the hypothesis that consuming large amounts of these nutrients will reduce prostate cancer," he added. "That is disappointing, but that is the overall message."
The findings are published in the September issue of the American Journal of Clinical Nutrition.
His team examined the effect of the blood levels of 10 micronutrients on the risk of developing prostate cancer for almost 2,000 males from eight European countries.
The research, which the authors call "the largest prospective study to date of plasma carotenoids, retinol, tocopherols, and prostate cancer risk," was part of the EPIC (European Prospective Investigation into Cancer and Nutrition) study, which includes more than half a million men and women.
The authors did find evidence to suggest that, once a cancer forms, high levels of lycopene (or of carotenoids in general, including lycopene) may reduce by about 60 percent the risk of the tumor progressing to an advanced-stage prostate cancer. Carotenoids appeared to have no effect on the rate of localized, earlier-stage disease, however.
According to Dr. Peter Scardino, head of the Prostate Cancer Program at Memorial Sloan-Kettering Cancer Center in New York City, prostate cancer is the most common cancer in men in the developed world. A Western male, he said, has about a 42 percent risk of developing cancerous cells in his prostate over his lifetime, a 16 percent risk of being diagnosed with the disease, and about a three percent risk of dying as a result. In other words, nearly one-quarter of Western males have a subclinical form of prostate cancer, which will never progress to more advanced disease.
Stopping progression is crucial. According to Scardino, for those whose disease does progress, the risk of death is much higher -- nearly 50 percent.
"I think it's an important study," Scardino said. That lycopene and bulk carotenoids reduced the risk of progressing to advanced disease without impacting the risk of developing prostate cancer overall, he said, "suggests maybe these micronutrients are not as important in [stopping] carcinogenesis as they are in [slowing] progression of a very small early tumor to one that becomes invasive and larger and develops the ability to metastasize."
"The study provides supportive evidence that lycopene and the carotenoids may have an effect on delaying the progression of prostate cancer, so, from that point of view, it is an interesting study," Scardino added.
But Alan Kristal, associate head of the Cancer Prevention Program at the Fred Hutchinson Cancer Research Center in Seattle, remained more skeptical. Though he called the study "well-executed," Kristal noted, for instance, that the authors were unable to control for prostate-specific antigen (PSA) testing among the men. These blood tests often detect clinically irrelevant tumors, he explained.
"You can never do an observational study of prostate cancer without rigorously controlling for whether or not the person got PSA screening," Kristal said. "The more times you take the test, the more likely you are to get the disease."
He also noted that the finding for lycopene contradicts a report published in May in Cancer Epidemiology Biomarkers and Prevention. That study did account for PSA testing, and it found no effect of lycopene whatsoever on prostate cancer risk -- including the risk of advanced disease.
"To my mind, that study is definitive," said Kristal. "It's a big study, extremely well executed, properly analyzed, and not biased by PSA screening."
A review of lycopene's effect on cancer by the U.S. Food and Drug Administration, published in July in the Journal of the National Cancer Institute, likewise found "no credible evidence to support an association between lycopene intake and a reduced risk of prostate, lung, colorectal, gastric, breast, ovarian, endometrial, or pancreatic cancer and very limited evidence to support an association between tomato consumption and reduced risks of prostate, ovarian, gastric, and pancreatic cancers," according to that study's authors.
So, with tomatoes, ketchup and pizza sauce crossed off the list of prostate-protecting foods, Key and others continue the search. Kristal, for instance, is on the executive committee of a randomized trial examining the effects of selenium and/or vitamin E on prostate cancer risk in 35,000 men. Results are expected in 2012, he said.
Said Key, "I am optimistic we will find something. This paper is an important piece of work, but it doesn't look like this is the answer."
According to a new study, neither carotenoids (such as lycopene), retinol, nor tocopherols (forms of vitamin E) appear to reduce the odds of prostate malignancy -- findings that are in line with two other recent publications.
"Our overall findings are null," said lead researcher Timothy Key, deputy director of the Cancer Research UK Epidemiology Unit at the University of Oxford, U.K.
"This large study does not support the hypothesis that consuming large amounts of these nutrients will reduce prostate cancer," he added. "That is disappointing, but that is the overall message."
The findings are published in the September issue of the American Journal of Clinical Nutrition.
His team examined the effect of the blood levels of 10 micronutrients on the risk of developing prostate cancer for almost 2,000 males from eight European countries.
The research, which the authors call "the largest prospective study to date of plasma carotenoids, retinol, tocopherols, and prostate cancer risk," was part of the EPIC (European Prospective Investigation into Cancer and Nutrition) study, which includes more than half a million men and women.
The authors did find evidence to suggest that, once a cancer forms, high levels of lycopene (or of carotenoids in general, including lycopene) may reduce by about 60 percent the risk of the tumor progressing to an advanced-stage prostate cancer. Carotenoids appeared to have no effect on the rate of localized, earlier-stage disease, however.
According to Dr. Peter Scardino, head of the Prostate Cancer Program at Memorial Sloan-Kettering Cancer Center in New York City, prostate cancer is the most common cancer in men in the developed world. A Western male, he said, has about a 42 percent risk of developing cancerous cells in his prostate over his lifetime, a 16 percent risk of being diagnosed with the disease, and about a three percent risk of dying as a result. In other words, nearly one-quarter of Western males have a subclinical form of prostate cancer, which will never progress to more advanced disease.
Stopping progression is crucial. According to Scardino, for those whose disease does progress, the risk of death is much higher -- nearly 50 percent.
"I think it's an important study," Scardino said. That lycopene and bulk carotenoids reduced the risk of progressing to advanced disease without impacting the risk of developing prostate cancer overall, he said, "suggests maybe these micronutrients are not as important in [stopping] carcinogenesis as they are in [slowing] progression of a very small early tumor to one that becomes invasive and larger and develops the ability to metastasize."
"The study provides supportive evidence that lycopene and the carotenoids may have an effect on delaying the progression of prostate cancer, so, from that point of view, it is an interesting study," Scardino added.
But Alan Kristal, associate head of the Cancer Prevention Program at the Fred Hutchinson Cancer Research Center in Seattle, remained more skeptical. Though he called the study "well-executed," Kristal noted, for instance, that the authors were unable to control for prostate-specific antigen (PSA) testing among the men. These blood tests often detect clinically irrelevant tumors, he explained.
"You can never do an observational study of prostate cancer without rigorously controlling for whether or not the person got PSA screening," Kristal said. "The more times you take the test, the more likely you are to get the disease."
He also noted that the finding for lycopene contradicts a report published in May in Cancer Epidemiology Biomarkers and Prevention. That study did account for PSA testing, and it found no effect of lycopene whatsoever on prostate cancer risk -- including the risk of advanced disease.
"To my mind, that study is definitive," said Kristal. "It's a big study, extremely well executed, properly analyzed, and not biased by PSA screening."
A review of lycopene's effect on cancer by the U.S. Food and Drug Administration, published in July in the Journal of the National Cancer Institute, likewise found "no credible evidence to support an association between lycopene intake and a reduced risk of prostate, lung, colorectal, gastric, breast, ovarian, endometrial, or pancreatic cancer and very limited evidence to support an association between tomato consumption and reduced risks of prostate, ovarian, gastric, and pancreatic cancers," according to that study's authors.
So, with tomatoes, ketchup and pizza sauce crossed off the list of prostate-protecting foods, Key and others continue the search. Kristal, for instance, is on the executive committee of a randomized trial examining the effects of selenium and/or vitamin E on prostate cancer risk in 35,000 men. Results are expected in 2012, he said.
Said Key, "I am optimistic we will find something. This paper is an important piece of work, but it doesn't look like this is the answer."
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