Articles about new Prostate Cancer drugs, treatment methods, research etc.


May 2007 - April 2008

Contents
*New Research Results Show That Investigational Drug Phenoxodiol Targets Cancer Protein, Causing Cancer Cell Death
*High Dose Radiotherapy Benefits Patients With Prostate Cancer
*EDAP And Duke Medical Restart Ablatherm-HIFU Localized Prostate Cancer Clinical Study
*Study Implicates Protein As A Trigger Of Advanced Prostate Cancer Recurrence
*Ablatherm? - HIFU: A New Perspective In 2007, The Year Of The First Long Term Clinical Results On The Treatment Of Localised Prostate Cancer
*UroToday.com Premiers Advanced Prostate Cancer Treatment Resource Center Covering Bone Health, Chemotherapy And Radiation Therapy
*Risk Of Prostate Cancer For Young Men With A Prostate Specific Antigen Less Than Their Age Specific Median
*Advanced Prostate Cancer And Heavy Multivitamin Use May Be Linked
*New Research Supports Early Testing For Prostate Cancer
*Web-Based Program Could Ease Treatment Decisions For Prostate Cancer Patients
*Warfarin And Prevention Of Prostate Cancer
*Statin Use Linked With Decreased Prostate Cancer Mortality Rates; Lower PSA Levels
*First Randomized Head-to-Head Study Shows Cryoablation At Least As Effective As External Beam Radiation For Treating Localized Prostate Cancer
*EDAP Fast-Tracks U.S. Clinical Trial For Non-Invasive Prostate Cancer
*Red Wine Protects The Prostate, From The Harvard Men's Health Watch
*Prostate Cancer: Clinical Study Demonstrates Superior Efficacy Of Docetaxel Chemotherapy
*Prostate Cancer Hospitalizations Declining, USA
*Exclusion Of Inflammation In The Differential Diagnosis Of An Elevated PSA: Considerations And Evidence
*The Surgical Management Of Localized Prostate Cancer: Opportunities And Limitations
*Radium-223: An Alternative Treatment For Prostate Cancer - The Lancet Oncology
*Prostate Cancer Screening Decreases The Absolute Risk Of Being Diagnosed With Advanced Prostate Cancer
*Protein Marker For Prostate Cancer Survival Identified By OHSU Cancer Institute Researcher
*Flaxseed Halts Prostate Cancer Growth New Study Shows
*Treatment For Early Prostate Cancer Associated With Type Of Specialist Seen
*Poniard Pharmaceuticals Announces Promising Data From Interim Safety Analysis Of Phase 1 Trials Of Picoplatin In Colorectal And Prostate Cancers
*Primary Therapy For Intermediate Risk Prostate Cancer: Any Differences In Outcomes, QOL, Or Salvage Options With Surgery Vs. Radiotherapy
*Castration Adapted Prostate Cancer: Androgen Metabolic Pathways In Recurrent Disease
*Omega-3s May Help Slow Prostate Cancer Growth
*Influence Of Androgen Suppression Therapy For Prostate Cancer On The Frequency And Timing Of Fatal Myocardial Infarctions
*Prostate Cancer-Specific Mortality After Radical Prostatectomy Or External Beam Radiation Therapy In Men With 1 Or More High-Risk Factors


 
New Research Results Show That Investigational Drug Phenoxodiol Targets Cancer Protein, Causing Cancer Cell Death

02 May 2007

A new study further supports the unique mechanism of action of phenoxodiol, an investigational drug being studied for the treatment of ovarian cancer. The drug appears to work by targeting a certain tumor-specific protein, which triggers a series of events that selectively induce cancer cell death. Phenoxodiol is currently being studied in patients with resistant ovarian cancer, a disease that is estimated to kill more than 15,000 women this year in the U.S. alone.

In studies conducted thus far, phenoxodiol has exhibited an excellent safety profile, with few patients experiencing side effects attributed to the drug.

The new research was conducted by a team headed by Research Professor Michael Berridge Ph.D., at the Malaghan Institute of Medical Research - New Zealand's leading medical research facility focused on finding cures for cancer and other diseases.

Findings from the study, to be presented at the New Zealand Society of Oncology meeting to be held May 9-11, help explain the mechanism by which phenoxodiol induces cancer cell death. This new research supports previous findings by Professor James Morre, Ph.D. at Purdue University, which showed that phenoxodiol interacts with the tumor-specific protein, tNOX, to selectively block cancerous cells from dividing by switching off a variety of pro-survival signaling mechanisms within the cancer cell, causing it to die.

In cases of late-stage ovarian cancer, standard chemotherapy drugs often have a limited duration of use. The cancer can progressively lose its sensitivity to chemotherapy until cancer cells become unresponsive causing resistance, a major barrier to successful cancer treatment. In laboratory studies and Phase II clinical trials, phenoxodiol showed promise in restoring drug sensitivity to resistant cancer cells.

"Phenoxodiol has a unique mechanism of action not exhibited by other anticancer drugs in current use.," said Dr. Berridge. "By inhibiting plasma membrane electron transport selectively in cancer cells, phenoxodiol subjects these cells to stress that leads to cell death. This novel drug and its related analogues have the potential to enhance anticancer efficacy by a different mechanism, promising a new approach to management of solid tumors in a range of clinical settings. As the first compound to operate via this pathway, confirmatory evidence to validate the mechanism of action is very desirable."

Specific Findings Identify Specific Proteins Associated with Unlocking the Mystery for Why Cancer Cells don't Die the Way Healthy Cells Do

Evidence from this new study indicates that phenoxodiol inhibits proliferation of many cancer cell lines and some primary immune cells. Phenoxodiol induces the destruction of cancer cells by disrupting a stress pathway in the outer cell membrane, causing down regulation of the FLICE-inhibitory protein, FLIP, and resulting in caspase-dependent and independent degradation of the X-linked inhibitor of cell death, XIAP.

Phenoxodiol selectively limits plasma membrane electron transport in cancer cells, by binding to a cancer specific surface plasma membrane electron transport element on cancer cells thereby inhibiting their proliferation, whereas the compound has no such effect on normal healthy cells.

Multinational trial underway

Phenoxodiol in combination with carboplatin is currently being studied in a multi-national Phase III clinical trial called OVATURE, following positive findings of previous trials conducted at Yale-New Haven Hospital. The OVATURE trial will take place in 60 sites in the United States, Europe, and Australia. Preliminary results from the trial are expected within 18 months.

About phenoxodiol:

Phenoxodiol is being developed as a therapy for late-stage, chemo-resistant prostate, ovarian and cervical cancers. Phenoxodiol is an investigational drug and, as such, is not commercially available. It is a novel-acting drug that inhibits key pro-survival signaling pathways operating via sphingosine-1-phosphate and Akt. Inhibition of these pathways leads to prevention of phosphorylation of key anti-apoptotic proteins such as XIAP. Loss of activity of these proteins restores the ability of chemoresistant tumor cells to undergo apoptosis in response to chemotherapy. The putative molecular target for phenoxodiol is a tumor-specific protein, accounting for the highly selective nature of the drug.
http://www.medilexicon.com/medicalnews.php?newsid=69537

High Dose Radiotherapy Benefits Patients With Prostate Cancer

04 May 2007

A higher dose of radiotherapy to treat patients with prostate cancer improves cancer control and reduces the need for salvage treatment compared with the results usually obtained with a standard dose of radiotherapy, say researchers in a trial reporting online today in The Lancet Oncology.

"The trial is important in emphasising the advantage of higher dose radiotherapy but also the need to continue to improve radiation techniques", says the chief investigator of the trial David Dearnaley of the Institute of Cancer Research and Royal Marsden Hospitals, Sutton, UK.

The researchers randomised 843 patients with prostate cancer to receive either a standard dose of radiotherapy (64 Gy) or an escalated dose of radiotherapy (74 Gy).

Dearnaley explains, "the dose increase was made possible by using a new more precise radiation treatment method called conformal radiotherapy".

The researchers found that the high dose of radiotherapy helped prevent the recurrence of prostate cancer, and reduced the need for additional hormone treatment. "However, the higher radiation dose did slightly increase bowel side effects", adds Dearnaley.

The Lancet Oncology
www.lancet.com
http://www.medilexicon.com/medicalnews.php?newsid=69843

EDAP And Duke Medical Restart Ablatherm-HIFU Localized Prostate Cancer Clinical Study

04 May 2007

EDAP TMS S.A. (Nasdaq: EDAP), the global leader in High Intensity Focused Ultrasound (HIFU) treatment of prostate cancer, announced the continuation of its US Phase II/III clinical trial with treatment of an additional two patients at Duke University Medical Center, Durham, North Carolina.

"We are excited to resume our US program," said Marc Oczachowski, CEO of EDAP. "EDAP's more than 10 years of experience in HIFU therapy plus extensive peer reviewed and published clinical references demonstrate the potential of HIFU in the US. We continue to show solid growth outside the US where Ablatherm-HIFU use is already approved and growing as Ablatherm achieves standard of care status in the treatment of localized prostate cancer in Europe, the only HIFU device able to demonstrate such progress and market adoption. Ablatherm is the true HIFU leader in Europe and clearly the preferred HIFU system. This success outside the US is due to our clear commitment to clinical excellence, and we have absolute confidence our US sites will adhere to the same high standards of excellence in the US study programs."

"HIFU appears to very well tolerated with minimal invasiveness and minor discomfort," states Cary N. Robertson M.D. F.A.C.S. Associate Professor, Division of Urology, Duke University Medical Center. "This technology offers an alternative to other approved therapies for prostate cancer and may be effective in selected individuals as a primary therapy. This is an important trial that will define the role of HIFU as a treatment for localized prostate cancer."

Further treatments are scheduled to follow immediately at multiple centers, with enrollment again open to patients meeting the study criteria.

The study is currently enrolling men over age 50 diagnosed with clinical stage T1a, b or c or T2a localized prostate cancer. HIFU is a noninvasive therapy using highly focused ultrasound energy to ablate the prostate tissue. Details of the study and background on Ablatherm-HIFU can be found online at http://www.clinicaltrials.gov by searching for "Ablatherm.".

"We observed a good initial start to the clinical study and a strong commitment to resume the clinical sessions at our centers due to their support for Ablatherm-HIFU," said Hugues de Bantel, in charge of the US FDA programs for EDAP. "We intend to complete multiple opportunities already presenting themselves to add centers and achieve full patient enrollment as rapidly as possible. We will achieve the clinical goals necessary to demonstrate the efficacy of Ablatherm-HIFU in the prostate cancer therapy spectrum for the US while advancing to standard of care status in Europe where the treatment is already approved."
http://www.medilexicon.com/medicalnews.php?newsid=69815

Study Implicates Protein As A Trigger Of Advanced Prostate Cancer Recurrence

11 May 2007

Scientists with the Lineberger Comprehensive Cancer Center at the University of North Carolina at Chapel Hill have for the first time implicated a growth-promoting cellular protein as one trigger of the inevitable recurrence of advanced prostate cancer in men who are undergoing drug treatment to shut down their sex hormones, or androgens.

The new research may help solve a mystery: why does prostate cancer recur in men treated to get rid of circulating androgens such as testosterone?

Moreover, because chemotherapy after recurrence extends life by only a few months, the new research, "raises the exciting possibility that we can develop a specific drug against this," said senior study co-author Dr. Young Whang, associate professor of medicine at UNC-Chapel Hill.

The study appeared online May 7, 2007, in the Proceedings of the National Academy of Sciences. It is slated for print publication in the journal on May 15.

The protein, named Ack1, is a member of the tyrosine kinase gene family. Ack1 exerts its effect on the reemergence of the cancer by biochemically altering the now inactive androgen receptor in the nucleus of prostate of cells, according to a series of experiments conducted by lead author Dr. Nupam P. Mahajan, assistant professor of pharmacology, and other Lineberger scientists. The kinase activates the receptor via phosphorylation by adding a phosphate group to this protein molecule.

"This biochemical action converts a prostate cell that would need an androgen signal for its growth to one that is independent of the androgen signal," said senior study co-author Dr. Shelton Earp, director of the cancer center, Lineberger professor of cancer research and professor of pharmacology and medicine.

Earp noted that until now scientists haven't completely understood what that conversion means. "Our experiments show that this heretofore understudied protein Ack1 may be crucial in at least a portion of these tumor recurrences. Nupam's study nails down the mechanism by which that conversion happens."

Among the experiments were those that involved mice that were unable to produce androgen. The animals were implanted with human prostate tumor cells containing an activated form of Ack1. "We found that when prostate tumor cells express activated Ack1, cancer grew aggressively in these mice," Mahajan said. "This mimics what happens in patients undergoing hormone therapy."

The researchers noted that approximately one-third of androgen-independent human prostate tumors contain an activated Ack1 molecule. "The study is telling us this is a target for therapy and perhaps a very important target for therapy," Earp said.

Other Carolina co-authors are Drs. Yuanbo Liu and Samarpan Majumder, Lineberger research associates; Maria E. Warren, molecular biology research associate; and Dr. Carol E. Parker, associate professor of biochemistry and biophysics. Dr. James L. Mohler, chairman of the department of urologic oncology at Roswell Park Cancer Institute in Buffalo, N.Y., and a UNC Lineberger member, also collaborated on the study.

Funding for the research came from the National Cancer Institute and the Elsa U. Pardee Foundation.

University of North Carolina at Chapel Hill School of Medicine
101 Manning Dr., 6002 East Wing
Chapel Hill, NC 27514
United States
http://www.unchealthcare.org
http://www.medilexicon.com/medicalnews.php?newsid=70578

Ablatherm? - HIFU: A New Perspective In 2007, The Year Of The First Long Term Clinical Results On The Treatment Of Localised Prostate Cancer

13 May 2007

UroToday.com - UroToday.com announced today the addition of Ablatherm? - HIFU: A New Perspective in 2007, the Year of the First Long Term Clinical Results on the Treatment of Localised Prostate Cancer to the UroToday.com HIFU (High Intensity Focused Ultrasound) Resource Center. The HIFU resource center includes all current publications, clinical information, clinical trials and media presentations related to HIFU treatment.

The clinical results are presented as follows:

Ablatherm? Long Term Results As A Salvage Option After Radiotherapy Failure By Pr. G. Conti MD, Como, Italy

Ablatherm? Efficiency on Long Term Results By F.J. Murat MD, Lyon, France

Ablatherm? Safety on Long Term Results By A. Blana MD, Regensburg, Germany

PSA Nadir: A Surrogate Marker Of Long-Term Efficacy in HIFU Therapy Localised Prostate Cancer By S. Brown MD, Stockport, UK

Visit the HIFU Resource Center and stay updated on clinical developments in HIFU and Prostate Cancer.

About UroToday UroToday.com attracts more than 45,000 readers monthly. The website covers over 22 urology disease categories and provides the most in depth Urological conference reports available online. UroToday.com is the world leader in delivering a quality, global online publication providing accurate and timely education that is clinically relevant in the practice of Urology. All scientific content is developed by urologists committed to translating research into clinically relevant science, including all genitourinary cancers, pediatric and geriatric urological dysfunctions for urologists, medical oncologists, advanced nurse practitioners and other medical professionals.

UroToday - the only urology website with original content written by global urology key opinion leaders actively engaged in clinical practice.

To access the latest urology news releases from UroToday, go to: www.urotoday.com
http://www.medilexicon.com/medicalnews.php?newsid=70792

UroToday.com Premiers Advanced Prostate Cancer Treatment Resource Center Covering Bone Health, Chemotherapy And Radiation Therapy

13 May 2007

UroToday.com - UroToday.com, (http://www.urotoday.com) announced today the launch of the Advanced Prostate Cancer Treatment Resource Center. The new Advanced Prostate Cancer Treatment Center focuses on bringing together resources of global Clinical publications, disease information, listings of Clinical Trials and relevant multimedia lectures related to Bone Health, Chemotherapy and Radiation in advanced disease. Urotoday's emphasis on these areas covers the spectrum of Advanced Prostate Cancer current clinical science and practice.

The resource center categorizes areas that focus on each type of treatment and supports the rapidly evolving insights that can positively affect advanced prostate cancer treatment and outcomes. The multimedia options, including some surgical interventions, will keep you abreast of the newest science and techniques as performed by leading urologists in the field.
http://www.medilexicon.com/medicalnews.php?newsid=70791

Quality Of Life After Surgery, External Beam Irradiation, Or Brachytherapy For Early-Stage Prostate Cancer
21 May 2007

UroToday.com- Without prospective, randomized data comparing oncologic outcomes of brachytherapy (BT), radiotherapy (XRT), and radical prostatectomy (RP), focus on patient quality of life (QOL) can potentially drive patient decision-making. In the online version of Cancer, Dr. Mark Litwin reports on a prospective QOL assessment of these 3 treatments performed between 1999 and 2003.

The treatment distribution was RP (307 men), XRT (78 men) and BT (90 men). Follow-up assessments were performed routinely over a 24-month period. General health related QOL (HRQOL) was performed with the Short Form-36 that consolidates 8 domains into physical and mental summary scores. The disease-specific QOL was evaluated using the UCLA prostate cancer index (PCI) and the AUA symptom score index. Surgical patients had their nerve sparing quantified by the surgeons. Short-term androgen deprivation therapy was given to 23% of the BT patients.

The data was reported on 475 participants (82%) who had complete follow-up assessments. Surgical patients were younger, but comorbidities did not differ among treatment groups. By treatment category, men reported to be potent prior to treatment were 51% in the RP group, 20% in the XRT group and 18% in the BT group. Participants who underwent a bilateral nerve-sparing RP had a greater initial loss of sexual function than those treated with XRT or BT, but the RP patients had greater long-term improvement. XRT patients were more likely than BT patients to return to baseline sexual function. Unilateral or non nerve-sparing RP were less likely than BT patients to return to baseline sexual function. Long-term sexual function scores were better among RP patients, but the baseline scores were much higher.

Post-treatment urinary bother was similar between RP and BT patients, but worse immediately after therapy than those treated with XRT. After 4 months there was no difference between groups. Up to one-third of BT patients had an exacerbation of obstructive urinary symptoms 24 months after therapy. RP had worse urinary control in the immediate post-op period, but continued to improve beyond 2 years after surgery. RP patients had minimal effect on bowel symptoms after RP.

Mark S. Litwin, John L. Gore, Lorna Kwan, Judson M. Brandeis, Steve P. Lee, H. Rodney Withers, Robert E. Reiter

Cancer 2007; epub
Reviewed UroToday.com Contributing Editor Christopher P. Evans, MD

UroToday - the only urology website with original content written by global urology key opinion leaders actively engaged in clinical practice.

To access the latest urology news releases from UroToday, go to: www.urotoday.com
http://www.medilexicon.com/medicalnews.php?newsid=71567

Risk Of Prostate Cancer For Young Men With A Prostate Specific Antigen Less Than Their Age Specific Median

21 May 2007

UroToday.com- The National Comprehensive Cancer Network recommendation for PSA screening is an initial PSA baseline at age 40 years, and if the value is below the age-related median of 0.7ng/ml, then the next screening PSA is not needed until age 45. If it is above 0.7ng/ml, then annual screening is recommended. Dr. Stacy Loeb and colleagues to include Dr. Catalona investigated this and in the May 2007 issue of the Journal of Urology report that men age 40-49 with a PSA less than the age specific median have a low risk of prostate cancer (CaP).

A total of 1,083 men age 40-49 with a family history of CaP or of black ancestry were identified in Dr. Catalona's CaP screening database. Mean age was 45 years and 50% were African-American. A positive family history of CaP was present in 57%. The median PSA for these men was 0.7ng/ml; 54% had a PSA below this value and 46% had a PSA above it. More men with a positive family history had a value above the median and a greater proportion of African-American men had a PSA below the median.

The likelihood of reaching the PSA threshold for a prostate biopsy was highly dependent on the baseline PSA level. PSA velocity was similar between those with a baseline PSA above and below the median, although 97% with a baseline below the median had a PSAV <0.75ng/ml, compared to 91% of participants with a PSA above the median. A total of 48 (4%) of these men underwent a prostate biopsy; 44 had a level above 0.7ng/ml and 4 had a baseline below 0.7ng/ml. Seven of these men had an abnormal DRE. CaP was detected in 26 men of whom 15 were African-American and 16 had a positive family history. Median age at diagnosis was 47 years and 25 of the 26 men diagnosed had a PSA above the age specific median at initial screening and 1 had a level below it. In the 25 men diagnosed with CaP and an initial PSA level above the median, the median PSA at diagnosis was 3.9ng/ml. The mean biopsy Gleason score was 6 and 24 underwent radical prostatectomy and 18 (78%) had organ confined disease with negative surgical margins. Biochemical progression had occurred in 6 men (24%).

In men age 40-49 with a baseline PSA level below the age-specific median of 0.7ng/ml, the annual percent change in PSA and PSAV were low, thus supporting the recommendations of the National Comprehensive Cancer Network.
http://www.medilexicon.com/medicalnews.php?newsid=71566

Advanced Prostate Cancer And Heavy Multivitamin Use May Be Linked

20 May 2007

While regular multivitamin use is not linked with early or localized prostate cancer, taking too many multivitamins may be associated with an increased risk for advanced or fatal prostate cancers, according to a study in the Journal of the National Cancer Institute.

Millions of Americans take multivitamins because of a belief in their potential health benefits, even though there is limited scientific evidence that they prevent chronic disease. Researchers have wondered what impact multivitamin use might have on cancer risk.

Karla Lawson, Ph.D., of the National Cancer Institute in Bethesda, Md., and colleagues followed 295,344 men enrolled in the National Institutes of Health-AARP Diet and Health Study to determine the association between multivitamin use and prostate cancer risk. After five years of follow-up, 10,241 men were diagnosed with prostate cancer, including 8,765 with localized cancers and 1,476 with advanced cancers.

The researchers found no association between multivitamin use and the risk of localized prostate cancer. But they did find an increased risk of advanced and fatal prostate cancer among men who used multivitamins more than seven times a week, compared with men who did not use multivitamins. The association was strongest in men with a family history of prostate cancer and men who also took selenium, beta-carotene, or zinc supplements.

"Because multivitamin supplements consist of a combination of several vitamins and men using high levels of multivitamins were also more likely to take a variety of individual supplements, we were unable to identify or quantify individual components responsible for the associations that we observed," the authors write.

In an accompanying editorial, Goran Bjelakovic, M.D., of the University of Nis in Serbia, and Christian Gluud, M.D., of Copenhagen University Hospital in Denmark, discuss the positive and negative health effects of antioxidant supplements. "Lawson [and colleagues] add to the growing evidence that questions the beneficial value of antioxidant vitamin pills in generally well-nourished populations and underscore the possibility that antioxidant supplements could have unintended consequences for our health," the authors write.
http://www.medilexicon.com/medicalnews.php?newsid=71121

New Research Supports Early Testing For Prostate Cancer

20 May 2007

Prostate cancer is the third-leading cause of cancer deaths among American men and is most treatable when caught in its earliest stages. Research presented during the 102nd Annual Scientific Meeting of the American Urological Association in Anaheim, Ca. provided further evidence supporting regular prostate-cancer screening and offered new insights into disease progression and the hormonal treatment of recurrent disease.

A SINGLE PSA MEASUREMENT IN MIDDLE AGE PREDICTS DIAGNOSIS OF ADVANCED PROSTATE CANCER UP TO 25 YEARS LATER IN AN UNSCREENED POPULATION (Abstract 1876)

Almost all advanced cancers could be found early by intense screening of at-risk patients, according to researchers from New York and Malmo, Sweden who analyzed samples taken from a population-based cohort of 21,277 men in Malmo, Sweden between 1974 and 1986 to determine whether initial PSA plasma levels correlated with future diagnosis of advanced disease.

Of the 21,277 cases, 498 men actually developed prostate cancer, and 161 suffered from advanced disease (greater than T3 or metastasis). Association between PSA levels and eventual development advanced disease was determined using conditional logistical regression. In men with a total PSA of .5, .75, 1., 1.5 and 2 ng/ml, the probability of being diagnosed with advanced disease by age 75 was 2 percent, 3 percent, 4 percent, 7 percent and 12 percent, respectively. Risk was highly concentrated, with 89 percent of advanced cancers occuring in men with the top 10 percent of PSA levels.

This abstract will be presented during Moderated Poster Session 59 on Wednesday, May 23 starting at 1:00 p.m.

CLINICAL AND PATHOLOGICAL FEATURES OF SCREEN VS. NON-SCREEN DETECTED PROSTATE CANCERS: IS THERE A DIFFERENCE" (Abstract 851)

Pathological stage and surgical margins are important predictors of prostate cancer recurrence after radical prostatectomy.

Cancers detected in a PSA-screening population from Tyrol, Austria, had a statistically significant lower rate of extracapsular extension and positive surgical margins than those found in a non-screened population despite similar preoperative PSA levels. Researchers evaluated 997 radical prostatectomy patients from Innsbruck undergoing surgery between February 1999 through March 2006. Within that group, 806 were participants in the PSA screening Tyrol Prostate Cancer Demonstration Project and 191 represented the non-screening group. Preoperative total PSA, age, pathological characteristics and prostate volume were analyzed. Screen-detected cancers were significantly more likely to be organ confined at the time of treatment with radical prostatectomy.

This abstract will be presented during Podium Session 29 on Monday, May 21 starting at 10:00 a.m.

BASELINE CHARACTERISTICS AND PREDICTORS OF PROGRESSION IN AN ACTIVE SURVEILLANCE COHORT: THE UCSF EXPERIENCE (Abstract 611)

Active surveillance with delayed intervention is a viable option for well-selected patients with favorable risk prostate cancer. But is there a single characteristic that could help determine which of these patients are likely to progress" What is the best predictor of subsequent intervention with treatment" To determine the best predictor of secondary treatment, researchers from the University of California, San Francisco (UCSF), examined demographic and clinical characteristics of men electing active surveillance.

The researchers led by Peter R. Carroll, M.D., characterized disease progression in a subset of men with low-risk disease enrolled in an active surveillance protocol at UCSF. Patients received repeat prostate needle biopsies at 12-24 month intervals, trans-rectal ultrasound (TRUS) every 6-12 months and PSA measurements every three months to track progression. Researchers defined progression as a change in PSA of greater than 0.75 ng/ml per year, increase in lesion size (as determined by TRUS) or change in Gleason sum. Of those three predictors, change in tumor grade was the most significant predictor of delayed intervention, with 35 percent of the subjects experiencing an increase in Gleason score on surveillance. There were no baseline demographic or clinical characteristics that could accurately predict disease progression in this population.

This abstract was presented during Podium Session 21 on Sunday, May 20.

OUTCOMES OF MEN MANAGED WITH WATCHFUL WAITING IN THE PSA FOLLOW-UP STUDY (Abstract 610)

There are many questions surrounding watchful waiting/active surveillance as an initial treatment for prostate cancer and whether outcomes vary from patients who elect a more aggressive treatment sooner after diagnosis. Researchers from Northwestern University, led by William Catalona, M.D., reviewed a large, community-based cohort of men with screen-detected prostate cancer electing watchful waiting as initial management for their disease.

A group of 347 men selecting watchful waiting as their initial treatment were followed with biannual PSA tests. Of this group, 36 percent showed evidence of biochemical progression and/or underwent secondary treatment. Overall mortality was 30 percent and disease-specific mortality was 8 percent. There were no deaths in the group electing secondary treatment while 8 died in the non-treatment group.

This abstract was presented during Podium Session 21 on Sunday, May 20.

INTERMITTENT ANDROGEN DEPRIVATION IN PATIENTS WITH PSA-RELAPSE AFTER RADICAL PROSTATECTOMY - FINAL RESULTS OF A EUROPEAN RANDOMIZED PROSPECTIVE PHASE III CLINICAL TRIAL (Abstract 600)

In men with PSA relapse following prostatectomy, androgen deprivation is commonly used to slow tumor progression. However, reducing androgen (namely testosterone) levels can seriously impact quality of life for patients undergoing this treatment. Researchers from Germany presented data comparing the use of continuous androgen deprivation (CAD) therapy to intermittent androgen deprivation (IAD) therapy in these patients to compare both efficacy and patient tolerability between these two forms of hormonal treatment.

No statistically significant difference was seen in androgen-independent disease progression between the two groups. However, patients treated with IAD had an improved quality of life and fewer hot flashes than the CAD group indicating that IAD may be a more attractive treatment option for patients with PSA relapse after primary treatment.

This abstract was presented during Podium Session 20 on May 20.
http://www.medilexicon.com/medicalnews.php?newsid=71551

Web-Based Program Could Ease Treatment Decisions For Prostate Cancer Patients

20 May 2007

A Web-based program that provides prostate cancer patients with information about different treatment approaches may make deciding which path to follow a little easier, Medical College of Georgia researchers say.

Treatments for localized prostate cancer and associated side effects are so varied that patients are often confused about which option is best for them, says Dr. Gerald Bennett, chair of the Department of Health Environments and Systems in the MCG School of Nursing.

"This disease can be treated by observation alone, surgery, cryosurgery, hormonal therapy and radiation therapies," Dr. Bennett says. "But there have only been a few studies that adequately compare the complications of different treatments, which can include sexual, bladder and bowel dysfunction. Men can hear their doctors' recommendations, but ultimately, they decide which treatment to pursue. Those decisions can dramatically affect their lives, but the bottom line is that we often don't know enough scientifically to recommend one treatment over the other."

MCG is part of a National Institutes of Health-funded study to determine the impact of the Personal Patient Profile Prostate (P4) program, an innovative computer program that measures personal factors and creates an Internet decision-support system.

Led by the University of Washington in Seattle, the other sites are Fox Chase Cancer Center in Philadelphia and the University of Texas Health Science Center in San Antonio. Nearly 500 patients will be included in the study nationwide.

In Augusta, Dr. Bennett and his research team will recruit 72 prostate cancer patients from the Augusta Veterans Affairs Medical Center. Half of those men will follow a traditional treatment plan - diagnosis followed by a consultation with a cancer specialist and treatment. The other half will use the P4 program.

"These men will go to the Web site and answer questions like who they feel should be responsible for making treatment decisions - their doctor, themselves or a combination of the two - and the program will provide video examples of how to approach those discussions with their care providers," Dr. Bennett says. "We believe men who have access to the P4 program will have less inner conflict while making treatment decisions and, in the long run, will be more satisfied with whatever treatment path they choose."

"I often see patients struggle with treatment decisions," adds Dr .Martha Terris, urologist at the Veterans Affairs Medical Center in Augusta and the Medical College of Georgia. "While a program like this one doesn't make the treatment decision for them, it does help them make better informed decisions and further open the lines of communication with their doctors."
http://www.medilexicon.com/medicalnews.php?newsid=71105

Warfarin And Prevention Of Prostate Cancer

20 May 2007

UroToday.com- A population based study by Dr. Tagalakis and colleagues suggest that a marginally lower risk of prostate cancer (CaP) in men on 4 years of warfarin therapy. This report appears in the May 2007 issue of the Lancet Oncology.

The population source was the Saskatchewan, Canada Cancer Registry and Saskatchewan Health, which comprise 99% of the one million Saskatchewan residents. ICD codes identified patients between 1981 and 2002 with any urogenital cancer to include prostate (11,502), bladder (3,424), kidney (1,601), uterine (1,800), and ovarian (1,085). For each case, six randomly selected controls without cancer were matched. Data on warfarin use was obtained from an outpatient prescription drug database. Warfarin ever-use and cumulative use were correlated with cancer risk. Conditional logistic regression was used to calculate matched odds ratios (OR).

Men with CaP and their matched controls had the highest prevalence of ever use of warfarin before the index date. This is consistent with the higher use of warfarin in men and increased use with increasing age. A marginally lower risk of CaP was found for men with 4 years of warfarin use compared with those who did not receive warfarin. Four years of warfarin usage in the 5-year period immediately preceding the index date was associated with a rate ratio of 0.80. A trend towards a decreasing rate ratio of CaP was found with increasing duration of warfarin use during years 2 through 5. For warfarin use, 76-100% of the time the rate ratio was 0.80 during year 2, 0.76 during year 3, 0.67 during year 4, and 0.81 during year 5. No other urogenital cancer was found to have an association with warfarin use. What is not assessed in this database is whether a selection bias against doing a prostate biopsy existed for men with an increased PSA who would require a change in anticoagulation regimen or temporary cessation of warfarin, while some of the other urogenital tumor can be diagnosed radiographically or without stopping anticoagulation. This would be potentially biased by the more indolent natural history of CaP.
http://www.medilexicon.com/medicalnews.php?newsid=71531

Statin Use Linked With Decreased Prostate Cancer Mortality Rates; Lower PSA Levels

22 May 2007

Urologists and researchers have postulated in recent years that statin medications could have an impact on the growth and progression of prostate cancer. Cholesterol is a primary building block for testosterone, which has in turn been linked with prostate tumor growth (less testosterone results in slower-growing tumors). In recent years, research has indicated a possible link between dietary fat intake and prostate cancer. Research presented at the 102nd Annual Scientific Meeting of the American Urological Association explores the effect statin medications (which work to reduce low-density lipoprotein, or LDL, levels) may have on prostate-specific antigen, the incidence of prostate cancer, and mortality due to prostate cancer.

EXPLORING CAUSES FOR DECLINING PROSTATE CANCER MORTALITY RATES IN THE UNITED STATES BETWEEN 1993 AND 2003 (Abstract 203)

Researchers from the University of Alabama, Birmingham, sought to compare declining prostate cancer mortality rates with the independent epidemiological variables including prostate-specific antigen (PSA) screening, insurance coverage, obesity, diabetes and hyperlipidemia (high cholesterol levels). Results of the study showed a direct correlation between prostate-cancer mortality rates with hyperlipidemia and PSA screening in white men, and health insurance coverage in black men. The link between high cholesterol and declining mortality was unexpected, and researchers attribute this relationship to the increased use of statin medications to treat high cholesterol.

THE INFLUENCE OF STATIN MEDICATIONS ON PROSTATE-SPECIFIC ANTIGEN LEVELS IN HEALTHY MEN (Abstract 463)

High levels of LDL cholesterol have been associated with a variety of health concerns, including heart disease and, most recently, prostate cancer. As more men are prescribed statin medications to lower levels of 'bad' cholesterol, prostate cancer growth has been shown to slow due to decreased levels of testosterone. Researchers from Duke University and Johns Hopkins University have explored whether statin medications affect not only prostate cancer growth, but also prostate-specific antigen levels in healthy men thereby posing a risk of not detecting the disease early.

The team examined 1,545 men who had been prescribed a statin between 1990 and 2006 at the Durham VA Medical Center. The men had a mean age of 60.1, median PSA of 0.92 ng/ml and mean pre-statin LDL level of 152 mg/dl. PSA changes were strongly linked with LDL changes; PSA levels declined by 1.1 percent for every 10 mg/dl decrease in LDL. Results suggest that statins influence prostate biology - a factor that should be explored further to examine the significance that statin medications may have on prostate cancer detection.

STATINS AND PROSTATE CANCER AMONG MEN PARTICIPATING IN THE FINNISH PROSTATE CANCER SCREENING TRIAL (Abstract 1719)

Reviewing PSA levels among statin users screened in the Finnish Prostate Cancer Screening Trial, researchers from Helsinki found a decrease in prostate cancer incidence in this group, compared to those who did not take the drugs. A significant decrease was found in the incidence of T3 cancers and thos with a Gleason score ranging 5-6. Researchers also found lower serum PSA levels and free/total PSA ratios in this population.

Non-statin, lipid-lowering drugs were not associated with incidence, stage or grade.

This abstract will be presented during Moderated Poster Session 53 on Wednesday, May 23 starting at 8:00 a.m.
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First Randomized Head-to-Head Study Shows Cryoablation At Least As Effective As External Beam Radiation For Treating Localized Prostate Cancer

23 May 2007

Endocare, Inc. (OTC Bulletin Board: ENDO), an innovative medical device company focused on the development of minimally invasive technologies for tissue and tumor ablation, announced today that a randomized clinical trial of 244 men with localized prostate cancer demonstrated that cryoablation, a minimally invasive method of freezing cancerous tumors to destroy them, is at least as effective as external beam radiation when used to treat localized prostate cancer. The trial is the first North American randomized clinical trial comparing two definitive prostate cancer treatments in the past 25 years to enroll more than 100 patients. In addition, it is one of 13 studies of the use of cryoablation for treating prostate and renal cancer scheduled to be presented this week at the American Urological Association (AUA) Annual Meeting that runs from May 19-24 at the Anaheim Convention Center in Anaheim, CA.

The head-to-head trial, led by Bryan J. Donnelly, M.D., a urologist at the University of Calgary, also showed that after 36 months, only 6.6 percent of the cryoablation patients had positive biopsy findings compared to 26.3 percent of the patients who underwent the radiation therapy.

"This study demonstrates that cryoablation is equivalent to external beam radiation when used to treat localized prostate cancer," said Dr. Donnelly, who presented the study at the conference. "Furthermore, the positive biopsy rates three years after treatment were significantly higher for patients who underwent radiation therapy. A positive biopsy alerts a physician to recurrent or residual disease within the prostate and indicates that additional treatment may be necessary. Like radiation therapy, cryoablation is a treatment option that should be considered by all patients who are diagnosed with localized prostate cancer."

Jay Fahrer, a spokesman for the Washington, D.C.-based Men's Health Network, a non-profit group of health professionals committed to improving the health and wellness of men, applauded the use of head-to-head, randomized studies of cancer treatment options.

"The decision that men face when diagnosed with prostate cancer is extremely difficult. This is largely because of the absence of studies directly comparing different treatment options. This landmark study settles the question of whether or not cryoablation is as effective as radiation therapy and solidifies its role as a primary treatment for prostate cancer. It is a much needed milestone in the collection of high-quality information regarding prostate cancer treatments and men's health choices," Fahrer said.

Other studies to be presented at the AUA were conducted by leading physicians from The Cleveland Clinic, MD Anderson Cancer Center, UC San Francisco Medical Center, Columbia University and other prestigious health care facilities. The studies include:

-- Primary Prostate Cryoablation: Results from 1,198 Patients Tracked with the COLD Registry: A retrospective study of 1,198 patients with an average age of 69 pooled from data of 27 physicians with a median follow-up of 25 months. The cryoablation patients had a positive biopsy rate of 6.8 percent, an ASTRO biochemical failure rate of 22.9 percent after five years, an incontinence rate of 2.9 percent and a fistula rate of 0.04 percent. The COLD Registry (also called the Cryo On-Line Database) is the largest database of cryoablation patients ever compiled and is based on an Institutional Review Board (IRB) approved protocol. J. Stephen Jones, M.D. of the Cleveland Clinic is the lead investigator.

-- Salvage Cryoablation for Recurrent Localized Prostate Cancer following Definitive Radiation Therapy (from COLD Registry): A retrospective study of 277 patients with an average age of 70 (all who had previously undergone radiation therapy and the cancer had recurred) pooled from data of 27 physicians with a median follow up of 25 months. The cryoablation patients had a positive biopsy rate of 6 percent, an ASTRO biochemical failure rate of 40 percent after five years, an incontinence rate of 3.4 percent and a fistula rate of 1.2 percent. Louis L. Pisters, M.D. of the University of Texas, M.D. Anderson Cancer Center is the presenting investigator.

-- Pre-operative Nomogram for Predicting Biochemical-Free Probability following Salvage Cryotherapy for Prostate Cancer: An analysis of 276 patients with locally recurrent prostate cancer who underwent salvage cryoablation therapy following the return of their cancer after radiation therapy (the majority had been treated with external beam radiation). The data suggest a pre-operative nomogram can be successful in predicting the success of salvage cryoablation in these patients. Philippe E. Spiess, M.D., of the University of Texas, MD Anderson Cancer Center is the lead investigator.

In addition to these and other studies highlighted at the Conference, the AUA is also offering a number of post-graduate courses and workshops that feature training and information on the use of cryoablation in the urology suite.

Endocare Chairman and Chief Executive Craig Davenport commented, "The continued production of quality data by leading physicians and the presence of AUA-sponsored cryoablation courses at this year's Annual Meeting mark the emergence of the cryoablation technology further into the mainstream of Urology and indeed all areas of medicine where minimally invasive treatments for cancer are needed."
http://www.medilexicon.com/medicalnews.php?newsid=71795

EDAP Fast-Tracks U.S. Clinical Trial For Non-Invasive Prostate Cancer

23 May 2007

EDAP TMS S.A. (Nasdaq: EDAP), the global leader in High Intensity Focused Ultrasound (HIFU) treatment of prostate cancer is fast-tracking its ongoing U.S. Ablatherm(R)- HIFU clinical trial. Long-term European results presented at the European Association of Urologists (EAU) in March paved the way for unprecedented interest from the U.S. medical community about Ablatherm-HIFU at The Annual Scientific Meeting of the American Urological Association (AUA) held last week in Anaheim, CA.

"We have treated more than 1,800 patients in our center over 10 years and we now have mature data that demonstrates the long-term benefits of Ablatherm- HIFU. Given the success we've had in Europe and the clear consensus from urologists that this therapy is a good selection for patients, it is a priority to make this leading-edge, non-invasive treatment available in the U.S.," commented Christian Chaussy, M.D. Department of Urology, Krankenhaus Muenchen-Harlaching, Germany. "We are also seeing more and more patients coming to Munich from the U.S. to receive Ablatherm-HIFU treatment," he added.

The U.S. Ablatherm-HIFU clinical study is currently enrolling men over 50 years of age, diagnosed with localized prostate cancer. Details of the study and background on Ablatherm-HIFU can be found online at http://www.clinicaltrials.gov by searching for "Ablatherm."

"The outstanding clinical outcomes demonstrated by the long-term European clinical data affirmed the early success we have seen with our patients who are currently enrolled in the U.S. trial," Cary N. Robertson M.D. F.A.C.S. Associate Professor, Division of Urology, Duke University Medical Center. "HIFU appears to be very well-tolerated with minimal invasiveness and minor discomfort."

How it works

The Ablatherm(R) Integrated Imaging device is designed to target and deliver high-intensity focused ultrasound (HIFU) energy to the prostate, resulting in thermal destruction of prostate tissue. It is intended for the primary treatment of localized prostate cancer in subjects with low risk, localized prostate cancer.

The focused energy is delivered from an endorectal probe containing ultrasound treatment and imaging transducers. Treatment with HIFU for low risk, localized prostate cancer subjects is expected to result in immediate thermal destruction of prostate tissue. The treatment is conducted under spinal or general anesthesia during one, two-hour session and patients are able to resume normal activity within 24 hours.

"The science is based on strong engineering principles. The HIFU device itself is elegant and very intuitive," added Cary N. Robertson M.D. F.A.C.S. Associate Professor, Division of Urology, Duke University Medical Center.

"We are dedicated to making Ablatherm-HIFU technology the next standard of care. The strong partnerships we have built with our U.S. investigators strengthen our commitment to saving countless patients from having to undergo radical treatment," commented Marc Oczachowski, CEO of EDAP. "This trial will enable U.S. physicians to provide their patients with the newest non-invasive option available for treating prostate cancer," he added.
http://www.medilexicon.com/medicalnews.php?newsid=71786

Red Wine Protects The Prostate, From The Harvard Men's Health Watch

23 May 2007

Researchers have found that men who drink an average of four to seven glasses of red wine per week are only 52% as likely to be diagnosed with prostate cancer as those who do not drink red wine, reports the June 2007 issue of Harvard Men's Health Watch. In addition, red wine appears particularly protective against advanced or aggressive cancers.

Researchers in Seattle collected information about many factors that might influence the risk of prostate cancer in men between ages 40 and 64, including alcohol consumption. At first the results for alcohol consumption seemed similar to the findings of many earlier studies: There was no relationship between overall consumption and risk. But the scientists went one step further by evaluating each type of alcoholic beverage independently. Here the news was surprising -- wine drinking was linked to a reduced risk of prostate cancer. And when white wine was compared with red, red had the most benefit. Even low amounts seemed to help, and for every additional glass of red wine per week, the relative risk declined by 6%.

Why red wine? Doctors don't know. But much of the speculation focuses on chemicals -- including various flavonoids and resveratrol -- missing from other alcoholic beverages. These components have antioxidant properties, and some appear to counterbalance androgens, the male hormones that stimulate the prostate.

Many doctors are reluctant to recommend drinking alcohol for health, fearing that their patients might assume that if a little alcohol is good, a lot might be better. The Harvard Men's Health Watch notes that men who enjoy alcohol and can drink in moderation and responsibly may benefit from a lower risk of heart attack, stroke, diabetes, and cardiac death.

Harvard Men's Health Watch
http://www.health.harvard.edu/men
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Prostate Cancer: Clinical Study Demonstrates Superior Efficacy Of Docetaxel Chemotherapy

24 May 2007

The chemotherapy drug docetaxel currently offers the best treatment for androgen-independent prostate cancer. That is the result of a now published clinical trial that compared the efficacy of the two most widely used chemotherapy drugs. When using docetaxel, the risk of disease progression was cut by more than 50% than when using the next-best chemotherapy drug.

The use of chemotherapy to treat prostate cancer has rapidly grown in importance over recent years, with several comprehensive clinical trials helping to drive forward progress. In two of these trials, the chemotherapy drug docetaxel offered patients a significantly improved prognosis. However, other clinical trials indicated that the drug vinorelbine, which like docetaxel acts on cellular microtubuli, also produces impressive results and it is often used as an alternative to docetaxel.

The Medical University of Vienna has now carried out the world?s first direct comparison of both drugs, giving doctors valuable support in choosing the appropriate treatment for their patients.

TWO DRUGS ONE CLEAR RESULT

The trial clearly demonstrated the superior efficacy of docetaxel by using 40 patients to directly compare the drug against vinorelbine. The initiator and coordinator of the study, Prof. Michael Krainer, oncologist at the Department of Internal Medicine I, Medical University of Vienna, describes the outcome of the trial: "The median time to disease progression in all 20 patients we treated with docetaxel was more than three times longer than in the patients given vinorelbine." Cancerous tumours in patients from the first group did not progress for an average period of 14.5 months. In contrast, the median time to first disease progression in the patients treated with vinorelbine was only 4.4 months.

Values for "prostate-specific antigen" (PSA), an established tumour marker that indicates when a cancer is progressing, were similarly conclusive. While 62.5% of the patients treated with docetaxel exhibited an over 50% reduction in PSA, a reduction of only 11.1% was detected among those treated with vinorelbine. This is a clear indication that docetaxel restricts tumour growth.

Even the team working on the study were surprised at the scale of the reduction in PSA produced by docetaxel. Prof. Krainer explains: "We used a much lower dose than that used during the TAX 327 study, which was the first to demonstrate the efficacy of docetaxel in a phase III trial, and we also chose not to boost the efficacy of the chemotherapy drug with cortisone premedication. Nevertheless, we still achieved a similar effect on PSA." Prof. Krainer believes this effect could be due to the lower toxicity which was produced by using a lower dose and which helped improve the efficacy of the therapy regimen.

Cancer specialist Dr. William K. Oh from the Dana-Farber Cancer Institute at Harvard Medical School also highlights this finding in his editorial comment attached to the publication. In his opinion, the therapy regimen used in Vienna offers a good alternative for patients in whom steroids are contraindicated. He also points out that the study demonstrated a 28.6% reduction of PSA in patients who had stopped responding to docetaxel and were instead using vinorelbine as second line chemotherapy, indicating that this drug will continue to play an important role in cancer treatment.

SMALL STUDY BIG ISSUE

This open-label, randomized phase II trial involved a total of 40 chemotherapy-na?ve patients with histologically proven androgen-independent prostate cancer. The patients were divided into two groups that were given 25mg/m2 weekly doses of docetaxel or vinorelbine. Referring to the scope of the trial, Prof. Krainer states: "Of course, smaller studies such as this phase II trial cannot produce definitive conclusions. These can only be generated by major phase III trials conducted at several centres. However, it is extremely important to establish in advance which of the treatments currently in use should be tested in such large-scale and expensive trials. Our impressive findings on docetaxel provide clear data for making this decision.?

Original publication:
A Prospective, Open Label, Randomized Phase II Trial of Weekly Docetaxel Versus Weekly Vinorelbine as First Line Chemotherapy in Patients with Androgen Independent Prostate Cancer
J. Urol., DOI:10-1016/j.juro.2007.01.148
Available to download at:
www.jurology.com/article/PIIS0022534707002868/abstract

Medical University of Vienna
1090 Vienna, Austria
www.meduniwien.ac.at
http://www.medilexicon.com/medicalnews.php?newsid=72007

Prostate Cancer Hospitalizations Declining, USA

25 May 2007

Men were less likely to be hospitalized for prostate cancer treatment in 2004 than in 1997, according to the latest News and Numbers from the Agency for Healthcare Research and Quality. Hospitalizations for treatment of the disease fell nearly 30 percent in those eight years.

Prostate cancer is the second-most common cancer in men. Currently, an estimated 2 million men in the United States are living with prostate cancer.

-- Approximately half the men hospitalized for prostate cancer treatment were 45 to 64 years old and men age 65 to 84 accounted for 44 percent. About 5 percent were older than age 85 and less than 1 percent were age 18 to 44.
-- Nearly 73 percent of these men underwent open prostatectomy - the most common procedure for the disease - and 13 percent had transurethral prostatectomy, a less invasive procedure often done on an outpatient basis.
-- Hospitals charged $1.7 billion for the stays of patients admitted for prostate cancer treatment. Almost half of this amount was billed to private insurers; 43 percent was billed to Medicare; 4 percent was billed to Medicaid; 1.5 percent was billed to uninsured patients and the remainder was charged to other payers such as the VA, military or other state programs.
-- During the same period, there was an 8 percent increase in the number of hospital stays for men who had prostate cancer but were being treated for other conditions.

This News and Numbers is based on data in Hospital Stays for Prostate Cancer, 2004. This report uses statistics from the HCUP Nationwide Inpatient Sample, a database of hospital inpatient stays that is nationally representative of all short-term, non-federal hospitals. The data are drawn from hospitals that comprise 90 percent of all discharges in the United States and include all patients, regardless of insurance type as well as the uninsured.

www.ahrq.gov
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Exclusion Of Inflammation In The Differential Diagnosis Of An Elevated PSA: Considerations And Evidence

26 May 2007

UroToday.com - Dr. Mark Litwin, UCLA moderated a session on "Exclusion of Inflammation in the Differential Diagnosis of an Elevated PSA: Considerations and Evidence" at the annual SUO meeting at the AUA. Dr. William Catalona, Northwestern University presented the lecture, which was followed by discussion.

Dr. Catalona stated that the median PSA of men without CaP should be 0.7ng/ml in men in their 40's, and increasing slightly as men get older. Overall, it is below1.7ng/ml for most men. For age 50-59, a PSA increasing above 0.9ng/ml is associated with significantly increasing risk. The natural variability of PSA is multifactorial and he focused on inflammation. The coefficient of variation of PSA is 15% when evaluated two weeks apart. Among 972 men who would have had a biopsy based upon initial PSA, 40-50% had a PSA fall below the biopsy level over time suggesting that a second PSA should be performed prior to biopsy. PSA velocity will be recommended as 0.35ng/ml/year based upon newer data.

PSAV is associated with increased detection of CaP but also associated with inflammation. He cited a study by Dr. Schaeffer in which in 42%f men treated with antibiotics, the PSA decreased to <4ng/ml afterwards. The mean decreased from 8.3 to 5.3ng/ml. 15% of CaP patients had a decreasing PSAV within 2 years prior to biopsy, while it was 25% for prostatitis.

64% of men who had an unchanged PSA after antibiotics had CaP compared to 35% who had a decrease in PSA. Up and down PSA levels are more indicative of inflammation, but the overall PSAV should prompt biopsy.

Dr. Scardino commented that there has never been a randomized trial of antibiotics and just rechecking the PSA alone will give a similar number of reductions in the PSA to avoid a biopsy. Dr Catalona responded that he believes up to 20% will not correct without antibiotics. Dr. Joel Nelson asked about the indiscriminate use of antibiotics and resistance, but Dr. Catalona felt the risk of this was justified in an individual to avoid a potential biopsy. He said the %free PSA is not changed by inflammation or antibiotics. Dr. Anthony D'Amico asked whether this is similar to use of finasteride, which has reportedly increased the detection rate and Dr. Catalona agreed that those patients who do not correct completely need a biopsy. He concluded that the use of antibiotics was not durable and had to be reemployed frequently.
http://www.medilexicon.com/medicalnews.php?newsid=72239


The Surgical Management Of Localized Prostate Cancer: Opportunities And Limitations

26 May 2007

UroToday.com - Dr. Marston Linehan, SUO president introduced Dr. Peter Scardino, MSKCC as the 2007 Willet F, Whitmore, Jr lecturer. Dr. Scardino's talk was titled "The Surgical Management of Localized Prostate Cancer: Opportunities and Limitations".

Dr. Scardino started by citing the Bill-Axelson trial that shows a decrease in metastatic rate, disease specific and overall survival in patients treated with RP vs. watchful waiting. He said RP provides excellent control of localized CAP. He thought overtreatment was an issue and RP should be reserved for CaP that poses meaningful threat. Among 6,490 patients having an RP at MSKCC since 1983 there is a freedom from PSA progression in 75%. The 15 year CaP specific survival rate is 93%. Even 40% of men with pT3 tumors are alive at 15 years and 45% with a PSA >20ng/ml are alive at 15 years.

He discussed the role of RP in high-risk CaP. In the literature up to 20% meet these criteria and 38% meet it using the criteria of PFAV>2ng/ml/yr. The 15 year freedom from progression in this group, however is above 45%. This suggests that perhaps avoiding RP in high risk patients is not appropriate.

The goals of RP are complete cancer removal, with minimal morbidity, early return to normal activities and no positive surgical margins or loss of continence or potency. However, nationwide the complications occur to a significant extent. Recovery of urinary continence was 96% and recovery of erections was 67%, and at 2 years only 60% are cancer free, continent and potent. He then evaluated to what degree outcomes are related to variables such as surgeon volume. While mortality did not differ among different surgical volumes, the incontintnece and impotency rates did. He showed a significant degree of heterogeneity regarding continence rates among surgeons at MSKCC. Positive surgical margins also differed among surgeons and this had significant implications for patients. Biochemical recurrence from 4 institutions (7,800 men) found that BCR was higher if a patient was operated on earlier in a surgeons' individual career. Also, a 5-year BCR of 18% was found for more inexperienced surgeons compared to 11% for experienced surgeons. Most disturbing said Dr. Scardino was that among those with high volume career total RP's, there was still variability. This points to differences in surgical technique. Fellowship trained and non-fellowship trained surgeons had similar outcomes at the onset of their careers, but fellowship trained urologists had improvement in outcomes to a greater extent than non-fellowship trained urologists. Research in surgical technique is an important area to continue to improve outcomes for patients.
http://www.medilexicon.com/medicalnews.php?newsid=72237


Radium-223: An Alternative Treatment For Prostate Cancer - The Lancet Oncology

03 Jun 2007

The bone-targeting radioisotope radium-223 has delivered promising results in a randomised trial to test its efficacy in treatment of hormone-refractory prostate cancer (HRPC). The findings are reported early Online - timed to coincide with presentation of the research at the American Society of Clinical Oncology meeting in Chicago - and in the July edition of The Lancet Oncology.

Patients who have HRPC often have involvement of bone marrow, leading to symptoms such bone pain, spinal-cord compression, and pathological fracture. Existing bone-targeted treatments, such as use of the beta-emitting radioisotope strontium-89 have been shown to reduce bone pain.

Dr Christopher Parker, Institute of Cancer Research and Royal Marsden Hospital, Sutton, UK and colleagues did a study of 64 patients with HRPC. Radium-223 was chosen because it emits alpha radiation - which has higher energy and travels less distance than beta radiation. Thus Parker and colleagues believe that alpha radiation will have a more pronounced localised effect on tumours.

The patients were randomly assigned to two groups. In the first, 33 received external-beam radiotherapy and up to four injections of radium-223. The other group received the same radiotherapy and placebo.

Levels of bone-alkaline phosphatase (bone-ALP) - considered a marker for progression of HRPC - decreased by 66% in the group receiving radium-223. The length of time for patients' HRPC to progress - as assessed by prostate-specific-antigen concentrations - was much longer for those receiving radium-223 (26 weeks) compared with the group given placebo (eight weeks). The median survival time for radium-223 patients was 41% longer than those receiving placebo (65?3 weeks vs 46?4 weeks respectively); and no radium-223 patients stopped treatment due to treatment toxicity.

However, radium-223 treatment had no significant effect on the timing of skeletal-related events (SREs) - another key indicator of HRPC progression. These include, among other factors, a 25% increase in pain severity, increased painkiller consumption, new pathological bone fractures, tumour-related orthopaedic surgical intervention, and use of radioisotopes to relieve new skeletal-related symptoms.

The authors believe larger clinical trials are needed to study the effect of radium-223 on SREs and overall survival rates for HRPC.

The authors say: "In our randomised study of patients with symptomatic, hormone-refractory prostate cancer, radium-223 was well tolerated with little or no myelotoxic effect, and showed promising evidence of efficacy."

They conclude: "Further studies of radium-223 should explore potential for escalation of dose and for increased duration of treatment by more than four injections. The bone-targeting properties of radium-223 could also be applicable to the treatment of skeletal metastasis from other primary cancers."

The Lancet Oncology
http://www.thelancet.com/journals/lanonc
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Prostate Cancer Screening Decreases The Absolute Risk Of Being Diagnosed With Advanced Prostate Cancer

03 Jun 2007

UroToday.com- Dr. Gunnar Aus and colleagues report in the March 2007 issue of European Urology that men screened for prostate cancer (CaP) had a 49% reduction in the risk of being diagnosed with metastatic disease compared to unscreened men.

The study included 10,000 men, ages 50-65 who were randomly invited for PSA screening and 10,000 randomized to serve as population-based controls. Men with a PSA >3ng/ml were asked to participate in a digital rectal examination, and transrectal ultrasound guided prostate biopsy. Those with a PSA level <3.0ng/ml were reinvited for PSA screening after 2, 4, 6 and 8 years. All patients diagnosed with CaP were treated according to local clinical practice.

Between the years1995 and 2004, 1,252 cases of CaP were diagnosed; 810 in the screening arm and 442 in the control arm. Men randomized to active screening had a 1.83-fold increased risk of being diagnosed with CaP compared to men in the control group. Most screened men had localized disease. The number of participants with metastatic CaP at the time of diagnosis (or with a PSA >100ng/ml) was 24 in the screening group compared to 47 in the control group (p=0.0084). This represents a 49% reduction in the risk of being diagnosed with metastatic CaP by screening over a 10-year period.

The study minimized selection bias as men were randomized without any prior information. A study limitation is that men had only sextant biopsy, although the biopsies were directly laterally.
http://www.medilexicon.com/medicalnews.php?newsid=72916

Protein Marker For Prostate Cancer Survival Identified By OHSU Cancer Institute Researcher

04 Jun 2007

Oregon Health & Science University Cancer Institute researchers have identified a protein that is a strong indicator of survival for men with advanced prostate cancer. The C-reactive protein, also known as CRP, is a special type of protein produced by the liver that is elevated in the presence of inflammation.

"This could mean that a simple blood test that is already available could help patients and doctors make better decisions as they become more informed about what to expect from the prostate cancer they are facing," said Tomasz Beer, M.D., director of the Prostate Cancer Research program at the OHSU Cancer Institute, associate professor of medicine, (hematology/medical oncology) OHSU School of Medicine.

Beer's research was presented at the 43rd annual meeting of the American Society of Clinical Oncologists in Chicago. Julie Graff, M.D., OHSU Cancer Institute member, division of hematology and medical oncology, will present the research.

It has been known that cancer causes an inflammatory response. This research also suggests that inflammation may play an important role in driving prostate cancer progression and resistance to therapy.

"While sometimes inflammation may slow the cancer, an increasing body of evidence suggests that cancer can take advantage of the inflammatory response and the inflammatory cytokines released by the immune reaction may in fact fuel cancer progression. To the extent that our hypothesis proves true, C-reactive protein may be reflecting the overall intensity of the inflammation," Beer said.

The finding that higher CRP is associated with shorter survival and a lower probability of response to chemotherapy is a result of a secondary analysis of inflammatory markers in subjects enrolled in the ASCENT study, a large Phase 2 clinical trial that evaluated treatment with docetaxel and DN-101, a high dose formulation of calcitriol or docetaxel with placebo. This analysis included subjects from both groups. The analyses were supported by Novacea Inc., the sponsor of the ASCENT study. This new finding was in collaboration with Novacea.

The results of ASCENT were published February 20, 2007 in the Journal of Clinical Oncology. . The most significant finding from the trial of advanced prostate cancer subjects was the magnitude of DN-101 (Asentar) used in combination with docetaxel (Taxotere), on survival, producing an estimated 49 percent improvement in survival (p=0.035), while reducing the frequency of serious adverse events by 34 percent (p=0.023) as compared to the use of Taxotere alone.

Because this was the first time CRP has been linked with both response and survival in advanced prostate cancer patients receiving chemotherapy, it will be important to confirm this finding in an independent data set before this can become a routine blood test for men with advanced prostate cancer, Beer said.
http://www.medilexicon.com/medicalnews.php?newsid=72899

Flaxseed Halts Prostate Cancer Growth New Study Shows

04 Jun 2007

A new US study suggests that flaxseed, which is rich in omega 3 fatty acids and lignans, can stop prostate cancer tumours from growing.

The study was presented at the 43rd annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago on Saturday by researchers from Duke University Medical Center, Durham, North Carolina.

The researchers think that flaxseed, which has similar properties to sesame seed, probably interrupts the chain of events that eventually makes cells multiply out of control and become a tumour.

Dr Wendy Demark-Wahnefried, a researcher in Duke's School of Nursing and lead investigator on the study said that:

"Our previous studies in animals and in humans had shown a correlation between flaxseed supplementation and slowed tumor growth, but the participants in those studies had taken flaxseed in conjunction with a low-fat diet."

However, she explained that:

"For this study, we demonstrated that it is flaxseed that primarily offers the protective benefit."

The study was funded by the National Institutes of Health, and researchers at the University of Michigan and the University of North Carolina at Chapel Hill also took part.

Demark-Wahnefried and colleagues recruited 161 men who were due to have surgery for prostate cancer (prostatectomy: where all or part of the prostate gland is removed).

The patients were randomly assigned to one of four groups. One group took 30 grams of flaxseed a day for an average of 30 days before they had the operation (the flaxseed only group). Another group did the same but also followed a low-fat diet (20 per cent or less of their calories from fat). A third group did not take the flaxseed and only followed a low-fat diet, while the fourth group, a control, had none of the interventions.

After the surgery, the researchers examined the tumour cells under a microscope to assess how quickly they had multiplied.

They then compared the men who had only flaxseed, with or without following a low-fat diet, with the men in the other two groups: no intervention and low-fat diet only. They found that the slowest rate of tumour growth occurred in the two flaxseed supplemented groups.

Demark-Wahnefried said:

"The results showed that the men who took just flaxseed as well as those who took flaxseed combined with a low-fat diet did the best, indicating that it is the flaxseed which is making the difference."

The flaxseed supplement was given in ground form because in the whole form the seed coat is hard and undigestible. The patients took the flaxseed either in drinks, sprinkled on food, or with yogurt.

Flaxseed is thought to stop the growth and spread of cancer cells. This could be because the omega-3 fatty acids it contains interferes with the ability of cancer cells to cling onto other body cells, said Demark-Wahnefried.

The lignans it contains may also have antiangiogenic properties, the ability to stop the blood supply to the tumour.

Demark-Wahnefried said that they were "excited that this study showed that flaxseed is safe and associated with a protective effect on prostate cancer".

In next phase of their research the team hopes to study the preventative properties of flaxseed, and its effect on patients with recurrent prostate tumours.

As well as being antiangiogenic, the lignans in flaxseed, one of the richest sources of these fibre-related compounds, are thought to interfere with or prevent cell division and affect hormones. They are antimitotic, affect androgen metabolism and have estrogenic effects, said Demark-Wahnefried.

Flaxseed is also the richest known source of plant-based omega-3 fatty acids which affect the production of cell membranes, the levels of natural killer cells and circulating levels of protein kinase C and tyrosine kinases, which profoundly affect cell activity.

According to the American Cancer Society, one in six American men gets prostate cancer. This year it is estimated that over 200,000 will be diagnosed with the disease and 27,000 will die from it.
http://www.medilexicon.com/medicalnews.php?newsid=72990

Treatment For Early Prostate Cancer Associated With Type Of Specialist Seen

04 Jun 2007

A new study analyzing men with localized prostate cancer shows that the specialty of the physician they see can influence the type of therapy they ultimately receive. The study, co-led by a urologist and a radiation oncologist at Memorial Sloan-Kettering Cancer Center, found that patients aged 65 to 69 years old who consult a urologist are more likely to undergo surgery to remove the prostate, while those who consult a radiation oncologist and a urologist, regardless of age, usually receive radiation therapy.

"These practice patterns are no surprise but are notable because specialists who treat prostate cancer tend to favor the treatment they themselves deliver, despite the fact that no one has shown one treatment for early stage prostate cancer to be better than another," said Thomas L. Jang, MD, MPH, a physician in the Department of Urology, at Memorial Sloan-Kettering and co-lead author of the study. "It is very important for patients to receive an unbiased, balanced perspective on the full range of treatments."

The study, presented at the annual meeting of the American Society of Clinical Oncologists, reviewed the records of 85,088 men aged 65 and older who were diagnosed with prostate cancer between 1994 and 2002 using information from the SEER (Surveillance, Epidemiology, and End Results) Medicare-linked database to determine the type of specialist they saw and the therapy they received. The treatments included radical prostatectomy (surgery to remove the prostate), radiation therapy, primary androgen deprivation (hormone) therapy, and expectant management (watchful waiting).

Among the men in the study, 50 percent were seen exclusively by a urologist; 44 percent by both a radiation oncologist and urologist; 3 percent by both a medical oncologist and urologist; and 3 percent by all three specialists. A high correlation was observed between the specialist patients saw and the treatment they received. This was especially true in the younger men aged 65 to 69 year old where 70 percent of men who saw only a urologist had a radical prostatectomy. However, if men in this group saw a radiation oncologist and a urologist, 78 percent had radiation therapy. If the men saw a medical oncologist and urologist, 53 percent had a prostatectomy and an almost equivalent number had either radiation therapy (17 percent), expectant management (16 percent), or primary androgen deprivation therapy (14 percent).

"Because outcomes for men are similar whether they have surgery or radiation therapy, there are often other factors that a patient considers when deciding their most optimal treatment," said Justin Bekelman, MD, a physician in the Department of Radiation Oncology at Memorial Sloan-Kettering and co-lead author of the study. "When speaking with physicians who have particular expertise in prostate cancer be they urologists, radiation oncologists, or medical oncologists men should seek a balanced perspective on the risks and benefits of all available therapeutic options."

"The treatments for early stage prostate cancer have different side effects, different recovery profiles, and involve a different commitment of time," said Deb Schrag, MD, a medical oncologist and health services researcher in Memorial Sloan-Kettering Cancer Center's Department of Epidemiology and Biostatistics and the study's senior author. "It is imperative that men be advised about the details of all options so that they can make an informed decision that is right for them."

In 2007, the American Cancer Society predicts that 218,890 men will be diagnosed with prostate cancer. The 5-year relative survival rate for men with localized prostate cancer is nearly 100 percent. Treatment side effects vary. The most common are urinary incontinence and erectile dysfunction for prostatectomy; diarrhea and erectile dysfunction for radiation therapy; loss of libido, hot flashes and breast tenderness for hormone therapy. There are no physical side effects associated with watchful waiting.

Drs. Peter T. Scardino, Michael J. Zelefsky, Colin B. Begg, Peter B. Bach, Elena B. Elkin, Ethan M. Basch, and Yihai Liu of Memorial Sloan-Kettering participated in this study. It was funded, in part, by grants from the National Institutes of Health and the National Cancer Institute.

Memorial Sloan-Kettering Cancer Center is the world's oldest and largest institution devoted to prevention, patient care, research, and education in cancer. Our scientists and clinicians generate innovative approaches to better understand, diagnose, and treat cancer. Our specialists are leaders in biomedical research and in translating the latest research to advance the standard of cancer care worldwide. For more information, go to http://www.mskcc.org.

Memorial Sloan-Kettering Cancer Center
1275 York Ave.
New York, NY 10021
United States
http://www.mskcc.org/mskcc/html/44.cfm
http://www.medilexicon.com/medicalnews.php?newsid=72972

Poniard Pharmaceuticals Announces Promising Data From Interim Safety Analysis Of Phase 1 Trials Of Picoplatin In Colorectal And Prostate Cancers

02 Jun 2007

Poniard Pharmaceuticals, Inc. (Nasdaq: PARD), a biopharmaceutical company focused on oncology, today announced promising results from an interim safety analysis of two Phase 1 dose-escalating trials of picoplatin, a new generation platinum for the potential first-line treatment of metastatic colorectal cancer (CRC) and metastatic hormone-refractory prostate cancer (HRPC). Initial safety data from the Phase 1 trial in CRC demonstrated that picoplatin can be safely administered with fluorouracil and leucovorin, and initial safety data from the Phase 1 trial in HRPC demonstrated that picoplatin can be safely combined with the dose of docetaxel (Taxotere(R)) used in current practice for HRPC.

The data were included in abstracts published in the 2007 American Society of Clinical Oncology (ASCO) Annual Meeting Proceedings.

-- Abstract #14510. Gladkov Jr O, Manikhas G, Biakhov M, Tjulandin S, Karlin D. Phase 1 study of picoplatin in combination with 5- fluorouracil and leucovorin as initial therapy in subjects with metastatic colorectal cancer.

-- Abstract #15546. Roman L, Karlov P, Kaprin A, Gladkov Jr O, Breitz H. Phase 1 study of picoplatin and docetaxel with prednisone in patients with chemotherapy-na?ve metastatic hormone refractory prostate cancer.

"Our new data indicate that picoplatin can be safely combined with established cancer therapeutics. In 66 patients treated up to 10 months, we have observed reversible myelosuppression that is non-cumulative and has not led to any treatment-related mortality," said Jerry McMahon, Ph.D., chairman and CEO of Poniard. "These Phase 1 studies have explored different doses of picoplatin and different dosing schedules either in combination with docetaxel for prostate cancer or with 5-fluorouracil and leucovorin for colorectal cancer. We anticipate that the Phase 2 trials for both indications will begin in the third quarter of 2007, shortly after the maximum tolerated doses have been defined."

He added, "In the Phase 1 colorectal cancer study, only three patients have experienced grade 1 neuropathy to date. There has been no neuropathy greater than grade 1 in all patients treated, including four patients who have received a cumulative picoplatin dose of greater than 900 mg/m2. The objective of our planned Phase 2 trial is to confirm the neuropathy-sparing properties of picoplatin given once every two weeks in a randomized trial compared to oxaliplatin and to enable a Phase 3 clinical trial to show superior safety and efficacy of FOLPI (picoplatin combined with fluorouracil and leucovorin) compared to FOLFOX (oxaliplatin combined with fluorouracil and leucovorin). The goal of our planned Phase 2 study in prostate cancer is to generate proof-of-concept data demonstrating that picoplatin has improved efficacy with docetaxel and to enable future picoplatin combination studies with taxanes for prostate and other cancer indications."
http://www.medilexicon.com/medicalnews.php?newsid=72878

Primary Therapy For Intermediate Risk Prostate Cancer: Any Differences In Outcomes, QOL, Or Salvage Options With Surgery Vs. Radiotherapy

26 May 2007

UroToday.com - Dr. Peter Carroll, UCSF moderated a session on "Primary Therapy for Intermediate Risk Prostate Cancer: Any Differences in Outcomes, QOL, or Salvage Options with Surgery vs. Radiotherapy" at the annual SUO meeting at the AUA. Dr. Eric Klein, Cleveland Clinic presented the lecture, which was followed by panel discussion.

Dr. Carroll began with presenting the definition and data on intermediate risk CaP and the treatment trends in the US. Regarding intermediate risk CaP he posed the questions; how do we define intermediate risk disease?, is this a spectrum of risk?, which such patients require combination treatment? and are there patients better suited for one form of treatment compared to another?

Dr. Klein presented data from the Cleveland clinic that showed that there is no difference in BCR between XRT and RP. Local recurrence rates favor RP patients, but this may be artifactual. A slight advantage to RP was found in surgical patients compared to XRT or brachytherapy. He cited a study with 24 month follow-up that accrued over 1,000 patients. 49% of men one year after RP had complaint of sexual dysfunction and 21% had urinary complaints after brachytherapy and 11% had bowel complaints after either form of XRT. Over time, side effects of RP improved with time, but obstructive symptoms from brachytherapy could persist. At 24 months the sexual QoL domains are similar, although patients who received radiotherapies had lower starting points. Obesity resulted in worse urinary and vitality outcomes for all forms of treatment. He summarized that cancer control at 53 months were similar among treatment groups but all therapies had detriments.

The panel consisted of Drs. Eric Klein, Anthony D'Amico, Harvard University, Derek Raghavan, Cleveland Clinic, and Gerald Andriole, Washington University. Discussion surrounding treatment monotherapy for intermediate risk disease yielded the point that recurrences after 10-15 years may pose some risk. The heterogeneity of this group of patients makes stratification of treatment complex, they agreed. The risks of monotherapy with potential recurrence was weighed against the toxicity and unproven outcomes of combination up front.
http://www.medilexicon.com/medicalnews.php?newsid=72240

Castration Adapted Prostate Cancer: Androgen Metabolic Pathways In Recurrent Disease

03 Jun 2007

UroToday.com - Dr. Peter Nelson, University of Washington presented "Castration Adapted Prostate Cancer: Androgen Metabolic Pathways in Recurrent Disease" in the session "New Ideas in Prostate Cancer Recurrence after Castration".

Dr. Nelson pointed out that between 2-10 years following androgen-deprivation therapy (ADT) androgen-independent (AICaP) clones will develop. This is partially due to mechanisms independent of androgens, with up to 5 pathways identified. These concepts work under the presumption that androgen levels have been adequately suppressed. However, clinically the meta-analysis of combined androgen blockade does demonstrate a small survival benefit using an anti-androgen.

He discussed that residual prostate androgens remain after a variety of endocrine manipulations. A GnRH antagonist given to patients resulted in a castrate level in 24 hours and greater reductions of testosterone and DHT in prostate tissue. This response is heterogeneous among individuals at the gene and protein levels. Analysis of neoadjuvant ADT radical prostatectomy tissue demonstrated that most genes examined are still active at the transcript and protein levels after 3-6 months of ADT. Using tissue from the rapid autopsy program, patients with untreated CaP have levels above the castrate level, but a significant number of metastatic castrate-treated patients do as well.

Xenografts grown in intact or castrate mice demonstrate that both have detectable androgen levels in the tumor tissue, despite the fact that rodents do not have significant adrenal androgen production. These tumors represent "castrate-adapted" CaP. In these tumors, transcripts for all the steroid molecules involved in the androgen synthesis pathway are still present. Numerous drugs are in development that targets the intracrine androgen pathways.
http://www.medilexicon.com/medicalnews.php?newsid=72920

Omega-3s May Help Slow Prostate Cancer Growth

22 Jun 2007

Research in mice suggests that a diet high in omega-3 fatty acids found in fish oil and certain types of fish could potentially improve the prognosis of men who are genetically prone to develop prostate cancer.

"This study clearly shows that diet can tip the balance toward a good or a bad outcome," said senior researcher Yong Q. Chen, Ph.D., from Wake Forest University School of Medicine. "It's possible that a change in diet could mean the difference between dying from the disease and surviving with it."

In mice that were engineered with a genetic defect that caused prostate cancer, a diet high in omega-3 fatty acids beginning at birth reduced tumor growth, slowed disease progression and increased survival. The research is reported online today by the Journal of Clinical Investigation and will appear in the July 2 print issue.

Prostate cancer is the most frequently diagnosed cancer and is a leading cause of death in men in the United States. Population studies have suggested that consumption of fish or fish oil reduces prostate cancer incidence. However, these investigations have been hampered by the difficulty people have in accurately reporting their dietary intake.

The goal of the current study was to explore gene-diet interactions in prostate cancer. It involved mice that were engineered with a genetic defect they lacked a tumor suppressor gene and spontaneously developed prostate cancer. This gene (Pten) is absent in 60 to 70 percent of metastatic cancers in humans.

The engineered mice and "wild-type" (or non-engineered) mice were fed varying levels of omega-3 and omega-6 polyunsaturated fatty acids (PUFAs). Both are "essential" fatty acids, which means the body needs them for proper cell function but cannot produce them. Many vegetable oils contain omega-6 PUFA. Fish like mackerel, lake trout, herring, sardines, albacore tuna and salmon are high in omega-3 fatty acids.

Nutritionists recommend that people consume equal proportions of omega-3 and omega-6 PUFA. However, in current western diets, the proportion of omega-6 to omega-3 is between 30 and 50 to one.

The mice were fed either a diet high in omega-3 (ratio of omega-6 to omega-3 was 1:1) a diet low in omega 3 (ratio omega-6 to omega-3 was 20:1), or a diet high in omega-6 (ratio of omega-6 to omega-3 was 40:1). The scientists compared survival rates and weighed the animals' prostates to measure tumor progression.

Mice with the tumor suppressor gene remained free of tumors and had 100 percent survival, regardless of diet. In mice with the gene defect, survival was 60 percent in animals on the high omega-3 diet, 10 percent in those on the low omega-3 diet and 0 percent in those on the high omega-6 diet.

"This suggests that if you have good genes, it may not matter too much what you eat," said Chen, a professor of cancer biology. "But if you have a gene that makes you susceptible to prostate cancer, your diet can tip the balance. Our data demonstrate the importance of gene-diet interactions, and that genetic cancer risk can be modified favorable by omega-3 PUFA."

Chen said dietary changes may be particularly beneficial in people prone to prostate cancer because the disease is usually diagnosed in older men and the tumors are slow-growing. It's possible that eating a high omega-3 diet could delay tumor development or progression long enough for the man to live out his natural lifespan with prostate cancer.

"Our data imply a beneficial effect of omega-3 PUFA on delaying the onset of human prostate cancer," Chen said.

He noted that the mice got lifetime exposure of omega-3 and that some people may not be willing to change their diets until they develop cancer. He hopes to study whether there would be beneficial effects of adding omega-3 PUFA to the diet after tumors have developed.

He cautioned that the effects were obtained with the omega-3s found in fish oil and that omega-3s from flaxseed oil and other plants may not provide the same results.

The research was funded by the National Institutes of Health. Co-researchers were Isabelle Berquin, Ph.D., lead author, Younong Min, B.S., Ruping Wu, B.S., Jiansheng Wu, Ph.D., Donna Perry, D.V.M., J. Mark Cline, D.V.M., Mike J. Thomas, Ph.D., Todd Thornburg, Ph.D., George Kulik, Ph.D., D.V.M., Adrienne Smith, B.S., Iris J. Edwards, Ph.D., and Ralph D'Agostino Jr., Ph.D., all with Wake Forest, Hao Zhang, Ph.D., with Southern Yangtze University in China, Hong Wu, Ph.D., with University of California Los Angeles School of Medicine, and Jing X. Kang, Ph.D., with Harvard Medical School.

Wake Forest University Baptist Medical Center is an academic health system comprised of North Carolina Baptist Hospital and Wake Forest University Health Sciences, which operates the university's School of Medicine. U.S. News & World Report ranks Wake Forest University School of Medicine 18th in primary care and 44th in research among the nation's medical schools. It ranks 35th in research funding by the National Institutes of Health. Almost 150 members of the medical school faculty are listed in Best Doctors in America.

Wake Forest University Baptist Medical Center
Medical Center Blvd.
Winston-Salem, NC 27157-1015
United States
http://www1.wfubmc.edu
http://www.medilexicon.com/medicalnews.php?newsid=74928

Influence Of Androgen Suppression Therapy For Prostate Cancer On The Frequency And Timing Of Fatal Myocardial Infarctions

25 Jun 2007

UroToday.com- Recent studies have suggested that patients treated with androgen deprivation therapy for more than 12 months may exhibit nearly a 50% risk of developing the metabolic syndrome. These data have heightened awareness regarding the potential cardiovascular toxicity of luteinizing hormone releasing hormone agonists in men with prostate cancer.

In the June 10th issue of the Journal of Clinical Oncology, D'Amico and colleagues present multi-institutional data evaluating the temporal relationship between androgen deprivation therapy and the risk of developing a fatal myocardial infarction in men with prostate cancer.

The cohort consisted of a total of 1,372 patients pooled from 3 randomized trials designed to evaluate the impact of the duration of ADT on the efficacy of radiotherapy administered for men with prostate cancer. The 3 studies included subgroups of men who had been randomized to receive radiation therapy with no ADT vs. 3 months of ADT, no ADT vs. 6 months of ADT, and 3 vs. 8 months of ADT. Clinical variables were evaluated to determine their association with the risk of a fatal MI.

The investigators found that in men age 65 years or older the use of ADT for 6 months was associated with a higher risk and a shorter time to a fatal MI when compared to men who did not receive ADT. The difference was not seen in men younger than 65 years of age.

These data retrospective obtained from randomized trials add to the growing body of evidence suggesting that androgen deprivation therapy is associated with an increased of the metabolic syndrome which may result in higher cardiovascular mortality. Androgen deprivation therapy is not free of adverse side effects and in older men its use should be limited to those patients with locally advanced or high grade prostate cancer whenever possible.
http://www.medilexicon.com/medicalnews.php?newsid=75115

Prostate Cancer-Specific Mortality After Radical Prostatectomy Or External Beam Radiation Therapy In Men With 1 Or More High-Risk Factors

25 Jun 2007

UroToday.com- According to a report by Dr. D'Amico and colleagues that appears in the online version of Cancer, a PSA velocity >2ng/ml/year is the high-risk factor most strongly associated with an increased risk of prostate cancer specific mortality (PCSM) after radical prostatectomy (RP) or radiotherapy (RT).

The researchers evaluated 948 men of whom 660 underwent RP and 288 had RT between 1998 and 2004. The patients had high-risk CaP as defined by having one or more of the following risk factors; Gleason score >7, PSA level >10ng/ml, clinical stage T2b or higher and PSAV >2ng/ml/year. Median patient age was 67 for RP men and 72 for RT men. Androgen deprivation therapy or adjuvant RT were exclusion criteria. Median follow-up was 5.4 and 4.0 years for RP and RT, respectively. Gray regressions were used for statistical analysis.

A single determinant of high-risk was associated with 68% of men treated with RP compared to 40% of those treated with RT. Patients with 2, 3, or 4 high-risk factors were at significantly increased risk for PCSM compared to men with any single high-risk feature. A pre-RP or post-RT PSAV >2ng/ml/year in the absence of other high-risk variables correlated with an increased risk of PCSM after surgery (HR of 7.3, 95% CI 1.0-59) or RT (HR of 12.1, 95% CI 1.4-105) compared to men with any other single high-risk feature.

Of patients treated with RP, 29 of 660 experienced PCSM; 2 of 5, 5 of 58, 11 of 149, and 8 of 448 of whom had all 4, any 3, any 2, or any 1 high-risk variable, respectively. Of patients treated with RT, 32 of 288 experienced PCSM; 10 of 25, 14 of 62, 3 of 85, and 5 of 116 of whom had all 4, any 3, any 2, or any 1 high-risk variable, respectively. Seven of 8(88%) and 4 of 5(80%) of all PSCM in RP and RT patients, respectively in men with a single high-risk factor had PSAV >2ng/ml/year as that variable. The data concludes that men with a PSAV >2ng/ml/year were found to have a significantly higher risk of PCSM compared with men who had any other single high-risk factor.
http://www.medilexicon.com/medicalnews.php?newsid=75112

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