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.

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.

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.

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.

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.

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.