Review Identifies Factors That Influence Patient Treatment Choice For Localized Prostate Cancer

UroToday.com - Variables that influence a patients' choice of treatment for localized prostate cancer (CaP) are identified in a literature review that is authored by Dr. Zeliadt and colleagues and appears in the on-line version of Cancer, 2006.

Cancer eradication is a primary concern for many men, but perhaps surprisingly not paramount to all patients. One study of 1000 CaP patients found that 42% defined an effective treatment as one that extended survival or delayed disease progression, but 45% defined effectiveness as preservation of quality of life (QOL). This contrasted to physicians, of whom 90% defined effectiveness as extended survival. In another study, only 20% of CaP patients selected either "effect of treatment of length of life" or "chances of dying of cancer" as 1 of the 4 most relevant factors in making a decision.

It is apparent that CaP patients associate cancer eradication with aggressiveness of therapy and radical prostatectomy (RP) was considered the most aggressive. One study found that 98% of RP patients and 50% of brachytherapy patients selected their treatment choice on the basis of evidence that it was the most curative procedure.

Regarding QOL, the issue of incontinence was more concerning than impotence. In fact, urinary and bowel side effects were the only 2 variables found to be important to greater than 50% of patients. Another study found that 49% and 38% of patients were concerned about incontinence and impotence, respectively. However, this must be assessed in the context of their pre-operative functional status. One report found that 55% of spouses reported that side effects were important, but only 6% indicated that side effects were deciding factors.

Only 2% of men indicated that out-of-pocket costs were important in selecting treatment choice. While spouses often are very involved in obtaining treatment information, one study found that only 13% of patients thought they would base their decision on family influence.

Clearly, patients are more involved in the decision making process. The same survey given to 2 cohorts of patients 5 years apart finds that more recently 32% as compared to 58% wanted their physician to make the final decision. Also, patients most commonly rely on the opinion of their urologist. While 37% sought a second opinion, 75% selected the first treatment recommended to them.

Review of studies regarding racial, socioeconomic and cultural factors reveal that African-American men more commonly receive less aggressive therapy. However, more educated men more commonly had watchful waiting presented to them, while higher income patients had surgery or brachytherapy discussed.

Many variables are found to influence a patients' selection of treatment for localized CaP. In addition to cancer eradication and QOL, clearly the initial physician a CaP patient interacts with regarding their new diagnosis of CaP is the most influential.

By Christopher P. Evans, MD

Reference:
Cancer. 2006 May 1;106(9):1865-74.
Link Here. Zeliadt SB, Ramsey SD, Penson DF, Hall IJ, Ekwueme DU, Stroud L, Lee JW

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Common Genetic Prostate Cancer Variant Is Identified

UroToday.com - Prostate cancer (CaP) is a presumed result of both genetic and environmental events. It is known that a positive family history and African-American ancestry will increase the risk of developing CaP 2-4 fold. This strongly supports a genetic alteration as a significant contributing factor. In the online version of Nature Genetics, the group working under Dr. Kari Stefansson in Iceland has reported a genetic variant on chromosome 8q24.

In the report, 3 genome-wide linkage studies were performed. The first used 1.068 microsatellite markers (repetitive stretches of short DNA sequences that occur in increased numbers in cancer cells) were typed for 871 Icelandic men with CaP that grouped into 323 extended families. This identified a suggestive linkage signal on chromosome 8q24. The researchers genotyped an additional 358 microsatellite markers spanning this region in 869 unrelated men with CaP and 596 population case-controls.

A second group of 422 Icelandic men with CaP and 401 controls was studied and the -8 variant was verified with an OR of 1.72 (p=0.0018). Combining the Icelandic groups demonstrated that the DG8S737 -8 allele variant had a frequency of 13.1% in affected men and 7.8% in controls. This corresponded to a population attributable risk of 11%.

Furthermore, 63 single nucleotide pleomorphisms (SNPs or single nucleotide alterations in a short genetic sequence) were geontyped and 37 were found significantly associated with CaP. Most associated were allele A of SNP rs1447295 (OR=1.72) and this correlated with the DG8S737 -8 allele.

The researchers attempted to replicate the findings in 1.435 unrelated men with CaP and 779 controls from Sweden and 458 European America men with CaP and 247 controls from Chicago. The frequency of the DG8S737 -8 allele variant was greater in affected men than in controls for all groups.

In the final study, 246 African-American men with CaP and 352 controls were genotyped and the frequency of the DG8S737 -8 allele variant was 23.4% in African American men with CaP and 16.1% in controls with an OR of 1.6. Of the SNPs evaluated in this study, rs1447295 gave the lowest, but not significant result suggesting that DG8S737 -8 rather than the SNPs is either itself a functional variant or is tightly associated with a presently unknown risk variant. In African-American men the association for affected individuals was 41% and 30% in the population, with a population attributable risk of 16% that may contribute to the higher incidence of CaP in African-American men.

An analysis of 510 Icelandic men with BPH did not show a significant excess of either the DG8S737 -8 allele or allele A of re1447295.

By Christopher P. Evans, MD

Reference:
Nat Genet. 2006 Jun;38(6):652-8. Epub 2006 May 7.
Link Here (PDF)

Amundadottir LT, Sulem P, Gudmundsson J, Helgason A, Baker A, Agnarsson BA, Sigurdsson A, Benediktsdottir KR, Cazier JB, Sainz J, Jakobsdottir M, Kostic J, Magnusdottir DN, Ghosh S, Agnarsson K, Birgisdottir B, Le Roux L, Olafsdottir A, Blondal T, Andresdottir M, Gretarsdottir OS, Bergthorsson JT, Gudbjartsson D, Gylfason A, Thorleifsson G, Manolescu A, Kristjansson K, Geirsson G, Isaksson H, Douglas J, Johansson JE, Balter K, Wiklund F, Montie JE, Yu X, Suarez BK, Ober C, Cooney KA, Gronberg H, Catalona WJ, Einarsson GV, Barkardottir RB, Gulcher JR, Kong A, Thorsteinsdottir U, Stefansson K

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Establishing An Integrated Molecular Signature Model For Metastatic Prostate Cancer

UroToday.com - Genomic and proteomic profiling has attempted to link patients with the likelihood for advanced disease progression. Approaches to do this are reviewed by Dr. Taylor and associates in the June 1, 2006 issue of Cancer Research.

Integrated approaches are of three types. One uses data available in the public domain rather than experimental, patient derived data and uses data-mining and bioinformatics. A second model integrates experimental data with heterogeneous public data sources. The third approach integrates multifaceted genomic and proteomic data for analysis of metastatic risk.

The paper reviews the integrated approach from the laboratory of Dr. Arul Chinnaiyan at the University of Michigan. Specimens from patients include benign, localized malignant and metastatic tissues that undergo direct proteomic analysis by an antibody-based high-throughput immunoblot approach. This methodology was validated with traditional immunoblotting and tissue microarray-based immunohistochemical staining. Correlation was also performed with prostate cancer transcriptomes to include publicly available genes expression studies and microarrays. Mapping between genes and dysregulated proteins resulted in data for meta-analysis by statistical procedures.

A 50-gene ensemble was identified that served as a multiplex signature of CaP progression when it was applied to patient primary disease specimens. The 50-gene signature was tested with two CaP gene expression studies and demonstrated strong concordance. The data suggests that mRNA transcripts that correlate with protein levels in metastatic disease could be applied as a multiplex gene predictor of CaP progression in localized disease. Application to other primary tumor types also supported relevance.

The integration of high-throughput data could also be extended to other proteomic platforms, such as mass spectrometry or array-based platforms.

By Christopher P. Evans, MD

Reference:
Cancer Res 2006;66:5537-39
Link Here.
Taylor BS, Varambally S, Chinnaiyan AM

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Symptom Severity Of PBS/IC Difficult To Predict Based On Medical History And Demographics

UroToday.com - The association, if any, between medical or demographic characteristics and symptom severity in chronic prostatitis/ chronic pelvic pain syndrome (CP/CPPS) and PBS/IC patients has not been well studied. Clemens and colleagues from Northwestern University reviewed their patient database covering 1999 to 2002 to identify patients diagnosed with CP/CPPS and IC. Questionnaires were mailed to these patients, and nonresponders were followed up 6 months later. The questionnaires asked for information on demographics, medical history, and smoking and alcohol intake. A standardized mental health questionnaire was administered, and females were sent the O'Leary Sant Symptom and Problem Indexes as well as the AUA Symptom Index. Men were sent the NIH chronic prostatitis symptom index.

Self-reported urinary urgency and frequency, depression and lower education level were independent predictors of symptom severity in men with CP/CPPS and women with PBS/IC. Self-reported pelvic pain, fibromyalgia and a previous heart attack predicted symptom severity in men and postmenopausal status predicted symptom severity in women. The authors conclude that although several common medical conditions are associated with urological pelvic pain syndromes in men women, few of them were predictive of symptom severity in this analysis.

By Philip M Hanno, MD, MPH
Reference:
Journal of Urology, 175:963-967, 2006
Link Here.
Clemens JQ, Brown SO, Kozloff L, Calhoun EA

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Time To Prostate Specific Antigen Recurrence After Radical Prostatectomy And Risk Of Prostate Cancer Specific Mortality

UroToday.com - Aside from preoperative PSA, Gleason score, and pathologic stage, surrogate markers for prostate cancer-related death after prostatectomy include PSA doubling time and the length of time from surgery to PSA recurrence.

In the October issue of the Journal of Urology, Freedland and co-workers from Johns Hopkins performed a detailed analysis of a contemporary series of 379 patients who developed disease recurrence after radical prostatectomy.

The authors found that disease-specific survival significantly decreased if the PSA recurrence occurred 3 years after surgery, with a hazard ratio of 2.70 (95% confidence interval, 1.37 to 5.31, p = 0.004). The 15-year estimated survival for patients with disease recurrence less than 3 years after surgery was 41% (95% CI 29 to 53) compared to 87% in those with recurrence 3 years after prostatectomy.

These data provide additional evidence that PSA recurrence within 3 years of surgery may serve as a surrogate marker for prostate cancer death. Most importantly, this information provides reassurance that the majority of patients with surgically-treated prostate cancer who recur after 3 years will not die of their disease.

J Urol. 2006 Oct;176(4 Pt 1):1404-1408.
Reviewed By UroToday.com Contributing Editor Ricardo F. SГЎnchez-Ortiz, MD

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Statin Use Associated With Decreased Risk Of Advanced Prostate Cancer

Use of cholesterol-lowering medications called statins is not associated with a lower risk of prostate cancer overall, but it is associated with a decreased risk of advanced disease, a large prospective study finds.

Two recently reported studies found an association between statin use and a reduced risk of prostate cancer. However, other observational studies and clinical trials have not confirmed those findings.

To investigate a possible association between statin use and the risk of prostate cancer and advanced prostate cancer, Elizabeth A. Platz, Sc.D., of the Johns Hopkins Bloomberg School of Public Health in Baltimore, Md., and colleagues analyzed data from the Health Professionals Follow-up Study, a cohort of 34,989 U.S. men ages 40 to 75. From 1990 to 2002, the men were asked every other year about several factors, including use of cholesterol-lowering drugs.

In 1990, 4.4% of the men reported taking statins. By 2000, that number increased to 23.8%. Current statin use was not associated with risk of prostate cancer overall or of localized disease. However, current use of statins was associated with a reduced risk of advanced prostate cancer. Compared with men who had never taken statins, men currently taking statins had half the risk of advanced disease and less than half the risk of metastatic or fatal disease. The authors calculated that the incidence of advanced prostate cancer among current statin users was 38 cases per 100,000 men per year, and 89 cases per 100,000 men per year among nonusers. The inverse association was even stronger for metastatic and fatal prostate cancers combined, and the reduced risk of advanced disease was even lower with longer use of statins.

A possible confounding factor of the study is that more statin users than nonusers reported undergoing prostate-specific antigen (PSA) screening, a test often used as an early indicator of prostate cancer. Men who underwent multiple PSA tests were more likely to be diagnosed with localized prostate cancer and less likely to be diagnosed with advanced disease. The authors calculated that PSA screening did not account for their results, but they caution that it may have been a source of bias in the analysis.

"- It is premature to recommend the use of statins for the prevention of advanced prostate cancer," the authors write. "Further work is needed to address the role of PSA screening as a possible explanation for these findings and to identify the biologic mechanisms that may underlie the inverse association, if this association is indeed causal."

Contact: Vanessa Wasta, Johns Hopkins Kimmel Cancer Center Office of Public Affairs

###

Other highlights in the December 20 JNCI

Note: The Journal of the National Cancer Institute is published by Oxford University Press and is not affiliated with the National Cancer Institute. Attribution to the Journal of the National Cancer Institute is requested in all news coverage. Visit the Journal online at http://jncicancerspectrum.oxfordjournals.org/.

Contact: Andrea Widener
Journal of the National Cancer Institute

Mucinous Adenocarcinoma Of The Prostate Does Not Confer Poor Prognosis

UroToday.com - While mucinous adenocarcinoma of the colon and breast demonstrate poor and favorable prognoses, respectively, the clinical behavior of mucinous adenocarcinoma of the prostate (MC) is unknown. A report by Dr. Lane and associates at the Cleveland Clinic suggest that the clinical course of MC is similar to conventional prostate adenocarcinoma (AC). This paper appears in the October 2006 issue of Urology.

Between 1987 and 2005, complete data on 2,572 radical prostatectomy (RP) patients who did not receive adjuvant therapy was available for analysis. A total of 32 cases were identified: 14 with MC and 18 with AC with focal mucin (AFM). Pathological and clinical variables were correlated with outcomes. All pathology was re-reviewed by a single pathologist.

In the MC cohort, pathologic Gleason score was 6 in one, 7 in 4, and 8 in three patients. In 6 patients it was not evaluable due to neoadjuvant hormonal therapy. Non-organ confined disease was present in 12 (37.5%) with MC or AFM including 12 with extraprostatic extension, 6 with positive surgical margins, and 4 with seminal vesicle invasion. One-half of patients had a pelvic lymphadenectomy and none had metastatic disease. There was no statistically significant difference between the patients with MC, AFM or AC with regard to PSA levels, clinical T stage, biopsy or pathologic Gleason score, or non-organ confined disease.

In follow-up, 26 patients had at least 2 follow-up PSA tests. Of these 26 men, biochemical failure occurred in 1 patient with MC and 5 patients with AFM (23%) at a median of 4.2 years. Overall survival showed no statistical difference among those with MC, AFM or AC. The 5-year overall survival rate was 100%, 100%, and 96.6%, for those with MC, AFM or AC, respectively. The overall 5-year biochemical recurrence-free survival rate was 100%, 69.2%, and 77.8%, for those with MC, AFM or AC, respectively.

This data is the largest known series of MC patients and suggests that MC can be treated in a fashion similar to AC.

Urol 2006;68:825-830

Reviewed By UroToday.com Contributing Editor Christopher P. Evans, M.D

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Study Suggests Role For Y Chromosome In Prostate Cancer

A new study finds that, among a group of men in Israel, men with only daughters had a 40 percent higher risk of prostate cancer than men with at least one son. The study raises the possibility that some mutation or variant on the Y chromosome may be involved in prostate cancer.

Although several studies have identified risk factors for prostate cancer and found some gene mutations that are associated with the disease, none of these can account for large numbers of prostate cancer cases. Some studies have suggested that prostate cancer risk may be associated with alterations on the X or Y chromosomes.

Because alterations on the sex chromosomes might affect the probability of having sons or daughters, Susan Harlap, M.D., of Columbia University in New York, decided to study cancer incidence and offspring among men participating in the Jerusalem Perinatal Study. During the study period, 712 men were diagnosed with prostate cancer. Compared with men who had at least one son, men with only daughters had a 40 percent increased risk of prostate cancer. Men with no daughters had no increase or decrease in prostate cancer risk compared with men with offspring of both sexes.

"Overall, our findings are consistent with hypotheses that tie Y chromosome loci to prostate cancer, although other explanations cannot be excluded," they write.

Contact: Stephanie Berger; Columbia University Office of Public Affairs

###

Other highlights in the January 3 JNCI

Note: The Journal of the National Cancer Institute is published by Oxford University Press and is not affiliated with the National Cancer Institute. Attribution to the Journal of the National Cancer Institute is requested in all news coverage. Visit the Journal online at http://jncicancerspectrum.oxfordjournals.org/.

Contact: Andrea Widener
Journal of the National Cancer Institute

Androgen Deprivation In Veterans With Prostate Cancer: Implications For Skeletal Health

UroToday.com- In addition to prostate cancer (CaP) patients with metastatic disease, androgen-deprivation therapy (ADT) is increasingly used for patients with non-metastatic recurrent disease. This means that the long-term consequences of ADT to include bone loss are more likely. Patients on ADT may also have other risk factors for bone loss to include alcohol abuse, smoking, prior fracture or a propensity for bone trauma secondary to falling. In the online version of the Annals of Pharmacotherapy, Dr. Wilcox and associates evaluated skeletal health in a population of Veterans on ADT at the Minnesota VA. They proposed three hypotheses; that fracture risk factors in addition to ADT would exist in most of these patients, bone mass measurements would be performed in a minority, and a minority of patients would receive bisphosphonate therapy.

Veterans over age 50 years who received ADT between 1993 and 2001 were identified through VA pharmacy service records. Medical records of these men were then reviewed. Of the 351 patients identified, 174 met study criteria. Median duration of ADT was 21 months and 57% received LHRH monotherapy without an anti-androgen. Additional skeletal risk factors were identified in 81% and smoking, alcohol use and prior fracture were most common.

Of the 174 men, only 22 (13%) had bone mineral density measurement (BMD) performed. Seven of these 22 men had BMD prior to initiation of treatment and 5 were found to be osteoporotic. The other 15 had BMD testing after initiation of ADT and 8 were osteoporotic after beginning ADT (median time 29 months). Fewer than half of the men received either calcium or vitamin D supplements for skeletal health and only 11% received antiresorptive therapy. Seventeen of the 22 men who had BMD measured received antiresorptive therapy. Fractures occurred in 24 men, most commonly vertebrae and hip. In those with fractures, 11 had one other risk factor for osteoporosis in addition to ADT. Only 6 of the patients with fractures were on antiresorptive therapy. The fracture rate was not different between men on combined androgen blockade or monotherapy.

This study found that in their population of Veterans on ADT, skeletal risk factors existed in 80%, BMD was infrequently measured and only 11% received antiresorptive therapy. Unfortunately, the analysis did not seem to determine whether patients were started on ADT for metastatic disease or non-metastatic disease. In the 24 men who experienced a fracture, the duration of their ADT prior to the fracture and whether the fracture was associated with a metastatic site on imaging was not reported.

Andrew Wilcox, Molly L Carnes, Timothy D Moon, Renee Tobias, Heather Baade, Emily Stamos, and Mary E Elliott
Annals of Pharmacotherapy 2006: 40: 2107 - 2114

Reviewed by UroToday.com Contributing Editor Christopher P. Evans, M.D.

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The Natural History Of Noncastrate Metastatic Prostate Cancer After Radical Prostatectomy

UroToday.com- Most patients with a rising PSA following relapse after primary therapy are treated with early androgen deprivation therapy (ADT). The natural history of these men therefore is not well defined. In the online version of European Urology, Dr. Yossepowitch and colleagues from Memorial Sloan-Kettering Cancer Center report that the median disease-specific survival from diagnosis of noncastrate metastases is 6.6 years.

The study cohort was comprised of 95 patients who developed metastatic disease without previously being treated by ADT for PSA relapse. Of these, 34 had received a short course of ADT before surgery, but testosterone was above castrate level at the time of metastatic presentation. Median follow-up was 7.1 years. Follow-up consisted of routine examinations, PSA testing, bone scans and additional imaging as indicated. At completion of follow-up, 33 men (35%) had died and in 29 of these the death was attributed to progressive castrate metastatic prostate cancer.

The mean interval from surgery to first evidence of metastatic disease was 4.2 years. Median PSA level at initial noncastrate metastasis was 13.5ng/ml and the median PSA doubling time was 3.4 months. At the diagnosis of metastasis, bone, lymph node and viscera were involved in 63%, 36%, and 6% of patients, respectively. Bone only metastases were found at initial metastatic diagnosis in 56 of 95 men (59%). Node-only metastases were identified in 30 patients (32%). The 3- and 5-year of cancer-specific survival from diagnosis of noncastrate metastases were 84% and 68%, respectively. In multivariate analysis, disease extent and PSA doubling time were significantly associated with survival outcome.

The 3- and 5-year actuarial disease-specific survival probabilities were 89% and 78% for a PSA doubling time of >3months and 71% and 42% for a PSA doubling time of <3 months, respectively. Only 26% of patients with extensive disease and a PSA doubling time of <3 months were alive 5 years after being diagnosed with noncastrate metastases, compared to 83% alive at 5 years who had minimal metastatic disease and a PSA doubling time of >3 months.

These data suggest that the risk of dying form prostate cancer is best determined from the initial pattern of metastatic spread and PSA kinetic, rather than time elapsing from prior disease states.

YossepowitchВ O, BiancoВ Jr.В FJ, EggenerВ SE, EasthamВ JA, ScherВ HI, ScardinoВ PT, GraefenВ M, LujГЎnВ M
Eur Urol 2006;epub
doi:10.1016/j.eururo.2006.10.045

Reviewed by UroToday.com Contributing Editor Christopher P. Evans, M.D.

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Radiation Therapy Combo Cures Prostate Cancer Long-Term

Seventy-four percent of men treated with a combination of radiation seed implants and external beam radiation therapy for prostate cancer are cured of their disease 15 years following their treatment, according to a study released today in the International Journal of Radiation Oncology Biology Physics, the official journal of ASTRO.

This study was conducted by the physicians at the Seattle Prostate Institute. Doctors wanted to look at the combination of seed implants and external beam radiation therapy, two different types of radiation therapy, to prolong the long-term disease cure rates for prostate cancer. Over the course of 15 years, doctors followed 232 men with early-stage prostate cancer who received a course of external beam radiation therapy followed by permanent seed implants a few weeks later. Sixty-five percent of these patients had T2b-T3 disease and the entire group had an average pre-treatment PSA of 15 ng/ml.

Seed implants, also called brachytherapy, are small radioactive pellets, each about the size of a grain of rice. The seeds are inserted into the prostate through small needles during a brief outpatient procedure. External beam radiation therapy involves a series of 25 short daily outpatient treatments, where a radiation oncologist precisely directs high energy radiation beams to kill cancer cells. "This study is exciting because it shows that the combination of brachytherapy and external beam therapy are successful long-term at curing men of their prostate cancer," said John E. Sylvester, M.D., lead author of the study and the Director of the Seattle Prostate Institute in Seattle. "This is good news for men with prostate cancer since radiation therapy is less invasive, spares healthy tissue and helps patients return to regular activities sooner than surgery."

For more information about prostate cancer treatment options, please visit http://www.rtanswers.org.

ASTRO is the largest radiation oncology society in the world, with more than 8,500 members who specialize in treating patients with radiation therapies. As the leading organization in radiation oncology, biology and physics, the Society is dedicated to the advancement of the practice of radiation oncology by promoting excellence in patient care, providing opportunities for educational and professional development, promoting research and disseminating research results and representing radiation oncology in a rapidly evolving socioeconomic healthcare environment.

American Society for Therapeutic Radiology and Oncology (ASTRO)
8280 Willow Oaks Corporate Dr., Ste 500
Fairfax, VA 22031
United States
http://www.astro.org/

Speeding Development Of Novel Tracer For Prostate Cancer

The collaborative work being performed by professionals across medical disciplines in the promising area of molecular imaging - from research scientists to nuclear medicine physicians, urologists, radiochemists and even veterinarians - provides encouraging news in fighting prostate cancer. This type of progressive - or translational - research can be seen in two papers published in the January issue of the Journal of Nuclear Medicine.

Researchers at Emory University in Atlanta, Ga., and at Nihon Medi-Physics’ research center in Chiba, Japan, collaborated closely in examining the potential of using the radiotracer FACBC to better stage or determine prostate cancer spread, said David M. Schuster, an assistant professor and director of the division of nuclear medicine and molecular imaging in Emory’s radiology department. "Our two studies show the progression of molecular imaging in what is called translational research, the process of taking research and finding useful applications for it with patients," added co-author of "Initial Experience With the Radiotracer Anti 1-Amino-3-[18F]Fluorocyclobutane-1-Carboxylic Acid (Anti-[18F]FACBC) With PET/CT in Prostate Carcinoma." Together with "A Preliminary Study of Anti 1-Amino-3-[18F] Fluorocyclobutyl-1-Carboxylic Acid for the Detection of Prostate Cancer," the two papers illustrate the development of a promising radioisotope tracer (a radioactive substance) from in vitro stage (in a test tube) to in vivo (within a live subject) in animals to in vivo in individuals with prostate cancer, explained Schuster. The Emory pilot study with FACBC, performed with only 15 patients, shows that the amino acid analog may hold the potential to provide information to better stage or determine prostate cancer spread, said Schuster. He stressed that FACBC is not available for use with patients, and additional research needs to be done with larger groups of patients.

Other than skin cancer, prostate cancer is the most common type of cancer found in American men. Estimates show that there were more than 230,000 new cases of prostate cancer in this country last year. Schuster’s study is one of many in which researchers are exploring new and "better" radiotracers that could improve a physician’s ability to stage cancer, for example, by providing higher sensitivity. This is very important since treatment and recovery outlook are dependent on the stage of cancer, said Schuster. "FACBC could eventually provide additional anatomical information about cancer location," he added, indicating that there could also be many "spin-off applications" for the tracer (for example, in patients with brain, breast and lung cancers). "This type of research is not a revolution, rather it’s an evolution; however, these kinds of evolutions can possibly lead to a revolution," explained Schuster, who is also seeking additional funding for this research.

The two studies used FACBC with positron emission tomography (PET) and PET with computed tomography (PET/CT), both standard imaging tools that can be used to pinpoint diseases in the body. When PET is used to image cancer, a radiotracer is injected into a patient, and it is drawn in higher concentrations to cancerous areas. The highly sensitive PET scan picks up the metabolic signal of actively growing cancer cells. The CT scan generates a detailed picture of internal anatomy, locating and revealing the size and shape of abnormal cancer growths. When these two results are fused together, the functional data from the PET imaging are correlated with anatomy on the CT images to provide a single detailed and informative image.

Tracers - such as 18F-FDG, 11C-choline, 11C-acetate and others - are currently used for diagnosing prostate cancer, said Shuntaro Oka, veterinarian and an assistant research associate at Nihon Medi-Physics. In Oka’s in vitro and in vivo study, FACBC had a high accumulation in cancer cells, small excretion into the bladder and a low accumulation in areas of inflammation, indicating that it could possibly "overcome drawbacks of some traditional PET tracers," he noted. "It is not unusual that the results of experiments lose touch with the results of clinical study; however, this time, the results of our basic studies correlated well with Dr. Schuster’s findings in patients with prostate cancer," said Oka. "This is good news for development of our compounds," he added, indicating clinical PET is not generally accepted in Japan; he hoped that FACBC could become "an agent to enhance the health and quality of life of patients."

Oka said the two research studies were definite examples of molecular imaging, a technique to visualize the activity of molecules in the body. PET showed the activity of amino acid transporters that "mediate" FACBC, the radiotracer that was developed in Mark M. Goodman’s lab at Emory University, into prostate cancer. " вЂ˜Hot spots’ on FACBC PET indicate the location of the amino acid transporters in target tissue and the site’s increased activity of the amino acid transporters," said Oka. Schuster indicated that the research was conducted with individuals representing "a panoply of clinical knowledge" from Emory Healthcare and Winship Cancer Institute of Emory University, Emory University, the Atlanta VA Hospital and Nihon.

The American and Japanese collaborative research appears in the January issue of the Journal of Nuclear Medicine, which is published by SNM, the largest molecular imaging and nuclear medicine association. Authors of "Initial Experience With the Radiotracer Anti 1-Amino-3-[18F]Fluorocyclobutane-1-Carboxylic Acid (Anti-[18F]FACBC) With PET/CT in Prostate Carcinoma" are David M Schuster, John R Votaw, Weiping Yu, Jonathon A Nye and Mark M. Goodman, Radiology Department, Division of Nuclear Medicine; Peter T Nieh, Viraj Master and Muta M. Issa, Urology Department; and F. DuBois Bowman, Biostatistics Department, all at Emory University in Atlanta, Ga.

"A Preliminary Study of Anti 1-Amino-3-[18F]Fluorocyclobutyl-1-Carboxylic Acid for the Detection of Prostate Cancer" was written by Shuntaro Oka, Ryota Hattori, Fumie Kurosaki, Masahito Toyama, Yasunori Yoshida and Osamu Ito, all with the Research Center, Nihon Medi-Physics Co. Ltd., in Sodegaura, Chiba, Japan; and Larry A. Williams, Weiping Yu, John R. Votaw and Mark M. Goodman, all with the PET Center and the Radiology Department at Emory University, in Atlanta, Ga.

About SNM - Advancing Molecular Imaging and Therapy

SNM is an international scientific and professional organization of more than 16,000 members dedicated to promoting the science, technology and practical applications of molecular and nuclear imaging to diagnose, manage and treat diseases in women, men and children. Founded more than 50 years ago, SNM continues to provide essential resources for health care practitioners and patients; publish the most prominent peer-reviewed journal in the field (the Journal of Nuclear Medicine); host the premier annual meeting for medical imaging; sponsor research grants, fellowships and awards; and train physicians, technologists, scientists, physicists, chemists and radiopharmacists in state-of-the-art imaging procedures and advances. SNM members have introduced - and continue to explore - biological and technological innovations in medicine that noninvasively investigate the molecular basis of diseases, benefiting countless generations of patients. SNM is based in Reston, Va.; additional information can be found online at http://www.snm.org/.

Contact: Maryann Verrillo
Society of Nuclear Medicine

Metastatic Disease Of Screen-Detected Prostate Cancer

UroToday.com- The number of men diagnosed with prostate cancer (CaP) per prostate cancer death (the incidence/mortality ratio) has increased due to either screening effort or improvements in treatment modalities. Due to a developing burden of overdiagnosis and treatment of CaP, a need for risk stratification of CaP patients exists. In the online edition of Cancer, the group of Dr. Fritz Schroeder, report on the prognostic factors related to the development of metastases in men with screen-detected CaP which is non-metastatic at diagnosis.

The European Randomized study of Screening for Prostate Cancer (ERSCP), Rotterdam database was used for this analysis. From 1993 to 1999 in Rotterdam 42,376 men were randomized between the screening and control arms. A cohort of 633 men diagnosed with non-metastatic CaP during their first screening visit in the first 4 years of ERSPC was identified. The primary endpoint for the analysis was the occurrence of metastatic disease and the secondary endpoint was overall survival.

Mean and median follow-up times for the 633 men were 7.1 and 7.5 years, respectively during which 41 men (6.5%) were diagnosed with metastatic disease. The 10-year metastatic-free survival was 90%. The mean time period from diagnosis until metastatic disease was 62 months. After 10 years the overall survival was 65%. A total of 232 men elected surgery and 5 (2.2%) developed metastatic disease.

In a multivariate regression model, the time to failure in surgery patients was significantly related to the initial PSA level (higher was worse). In the 334 men treated with radiotherapy, the group with a Gleason score >8 and, jointly a higher total number of biopsy cores positive for cancer showed a different failure pattern when compared to the rest of the radiotherapy patients. These patients had earlier time to metastases.

The data suggest that the predictive potential of the total number of biopsy cores with CaP and the biopsy Gleason score strongly affects the time to metastases during the first 60 months of the follow-up, but the initial PSA level and poorly differentiated tumors are the only predictors for metastases occurring after 60 months.

While the development of metastases is not common in men with screen-detected CaP, individual risk factors can help to predict for metastatic recurrence.

Stijn Roemeling, Ries Kranse, André N. Vis, Claartje Gosselaar, Theo H. van der Kwast, Fritz H. Schröder
Cancer: VolumeВ 107, IssueВ 12, Date:В 15 December 2006, Pages:В 2779-2785

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A Meta-Analysis Of Diabetes Mellitus And The Risk Of Prostate Cancer

UroToday.com- In 2004 a meta-analysis reported that patients with diabetes mellitus (DM) had a statistically significant decrease in risk (9%) of developing prostate cancer (CaP). This has now been validated in a larger meta-analysis reported by Drs. Kasper and Giovannunucci from Harvard Medical School. Their report appears in the November 2006 issue of Cancer Epidemiology Biomarkers and Prevention.

The goal of the new meta-analysis was to increase the number of articles included in the analysis from 14 to 19 and thereby the number of cases from 9,000 to >20,000 for enhanced statistical analysis. The authors also sought to determine if differences existed in patients in the pre-PSA compared to PSA era. The selection of published studies identified 325 articles of which 19 were chosen for extraction and analysis. While most publications did not specify whether patients had type I or type II DM, the age of participants suggested that most had type II DM. A variety of subset analyses were performed to address particular questions.

To determine the amount of heterogeneity that existed between the 19 studies a Cochran's Q test was performed. Then using a random-effects model, the authors found that DM was associated with a lower risk for CaP (RR, 0.84). Both cohort and case-control studies demonstrated heterogeneity. When analyzed by publication year, less heterogeneity existed as a group for the studies published prior to 2002 or after 2002 compared to all the studies combined.

To determine any difference in risk in the pre- and post-PSA eras, another subgroup analysis was done. The RR for pre-PSA was 0.94 and the RR for PSA era was 0.73. Separating studies that corrected for BMI from those that did not correct for BMI showed RRs of 0.82 and 0.87, respectively. Overall, the study showed that diabetic men have a statistically significant 16% decreased risk of developing CAP. The authors cite several possible explanations. DM and CaP may share additional factors that affect the risk of both diseases independently. This could include decreased insulin and IGF-I levels, or decreased testosterone levels.

This larger, robust meta-analysis strongly validates that men with DM are at decreased risk for development of CaP.

Jocelyn S. Kasper and Edward Giovannucci
Cancer Epidemiol Biomarkers Prev 2006 15: 2056-2062.

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Impact Of Surgical Margin Status On Long-Term Cancer Control After Radical Prostatectomy

UroToday.com- Patterns of prostate cancer (CaP) recurrence following radical prostatectomy (RP) demonstrate that up to 50% of patients will develop a high PSA level by 10 years after RP with most occurring within the first two years, but 20% occurring at greater than 5 years. Surgical margin status may impact this and is related to surgical technique, argues Dr. Orvieto from the University of Chicago who reports on the surgical series of Dr. Charles Brendler in the BJU International.

Between 1994 and 2004 a cohort of 996 men underwent RP by Dr. Brendler for clinically localized CaP. Mean patient age was 60 years and no patient received either neoadjuvant therapy or adjuvant therapy before biochemical failure. Pelvic lymph node dissection was performed in 44.5%. During pathologic review, any tumor at the inked margin was noted as a positive surgical margin (PSM), which was defined as focal if a solitary PSM and extensive when multifocal PSM was reported. Biochemical recurrence (BR) was defined as a PSA >0.1ng/ml and confirmed on a repeat assay.

Clinical stage was T1c in 60% and T2 disease in 40%. Ninety percent of patients had Gleason score 5-7 tumors on biopsy. Overall, a PSM was identified in 88 of 996 cases (8.8%). Only 12 of 694 patients with organ-confined disease (1.7) had a PSM. In those with extra-capsular extension, 60 of 241 (24.9%) and 16 of 59 (27%) with pT3a and pT3b disease had a PSM, respectively. Both clinical stage and pathological stage were statistically correlated with incidence of a PSM. Higher post-operative Gleason score did not correlate. The authors state that surgical modifications in 1995 and 2000 were followed by a significant decrease in PSM rates over time in patients with extra-capsular extension.

Overall, 97% of the cohort was available for follow-up at a mean of 6.4 years, during which 98 patients (10.1%) developed BR. Of these, 37% experienced a BR within a year of surgery and 61% with the first 2 years. Only 12% had a BR after 5 years from RP. The mean time to BR was 2.4 years. Follow-up was available in 871 men (90%) at 5 years and 135 men (14%) at 10 years. Kaplan-Meier analysis showed 5- and 10-year biochemical disease free survival rates of 90% and 86%, respectively. Adjuvant therapy was given to 89 men (9.2%) after RP. Nine men died from CaP.

Biochemical progression developed in 69 of 883 patients (8%) with negative surgical margins compared to 29 of 85 men (34%) with a PSM. Ten-year biochemical disease-free survival estimates for negative and positive surgical margins were 90% and 60%, respectively. A PSM was a significant predictor of recurrence in patients with both organ confined and pT3a disease. However, the risk of BR in those with pT3b disease was not impacted by the presence of a PSM. On multivariate analysis, the presence of a PSM and final pathological stage and Gleason score were the strongest predictors of subsequent BR.

Marcelo A. Orvieto, Nejd F. Alsikafi, Arieh L. Shalhav, Brett A. Laven, Gary D. Steinberg, Gregory P. Zagaja, Charles B. Brendler
BJU InternationalВ 98В (6),В 1199-1203.
Reviewed by UroToday.com Contributing Editor Christopher P. Evans, M.D.

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Copyright © 2006 - UroToday

Risk Of Dying From Prostate Cancer Increased By Excess Weight And Adult Weight Gain

A new study finds that obesity increases the risk of death from prostate cancer, even though it does not increase the overall risk a man will be diagnosed with the disease. Published in the February 15, 2007 issue of CANCER, a peer-reviewed journal of the American Cancer Society, the study reveals that higher body mass index (BMI) and weight gain in adulthood correlated strongly with increased risk of death from prostate cancer. However, no such association was found between BMI or weight gain and the development of the cancer. The study is the first large, prospective study to identify increasing weight after age 18 as an independent, poor prognostic factor for prostate cancer.

The incidence of obesity has increased dramatically worldwide. In the U.S., for example, the number of states reporting obesity rates greater than 20 percent increased from zero in 1985 to 46 in 2005. Today, 30 percent of American adults are categorized as obese - i.e., a BMI greater than 30. Obesity is linked to chronic medical problems, including heart disease, diabetes, gallbladder disease, and stroke. In addition, studies indicate higher BMIs are linked to some cancers, including breast and colorectal cancer.

The influence of obesity and weight gain on the development of localized and aggressive forms of prostate cancer is not clear. A recent meta-analysis suggested only a weak correlation between obesity and prostate cancer incidence. However, clinical studies have suggested that men with higher BMI or men who gained weight most rapidly since age 25 were at greater risk of treatment failure or being diagnosed with advanced disease.

Led by Margaret E. Wright, Ph.D., of the Division of Cancer Epidemiology and Genetics at the National Cancer Institute in Bethesda, MD, researchers followed 287,760 men, ages 50-71 years as part of the NIH-AARP Diet and Health Study to examine the individual impact of BMI and adult weight change on the incidence, severity and outcome of prostate cancer.

The researchers found that higher BMI and weight gain since the age of 18 were associated with significantly higher risk of death from prostate cancer. As BMI increased, so did the relative risk of death. Men who were overweight (BMI 25-29.9) had a 25 percent higher risk, mildly obese men (BMI 30-34.9) had a 46 percent higher risk, and severely obese men (BMI greater than 35) had a 100 percent, or doubled risk. Similarly, men who gained weight since the age of 18 were also at increased risk of a fatal outcome. Neither overweight nor obesity, however, was associated with developing prostate cancer.

That obesity did not impact the incidence of prostate cancer is consistent with findings from most other studies. However, that "BMI and adult weight gain were each linked with higher prostate cancer mortality," significantly links "adiposity to prostate cancer progression leading to death," conclude the authors.

###

Article: "Prospective Study of Adiposity and Weight Change in Relation to Prostate Cancer Incidence and Mortality," Margaret E. Wright, Shih-Chen Chang, Arthur Schatzkin, Demetrius Albanes, Victor Kipnis, Traci Mouw, Paul Hurwitz, Albert Hollenbeck, Michael F. Leitzmann, CANCER; Published Online: January 15, 2007 (DOI: 10.1002/cncr.22443); Print Issue Date: February 15, 2007.

Contact: David Greenberg
John Wiley & Sons, Inc.

The Prognostic Significance Of Perineural Invasion In Prostatic Cancer Biopsies

UroToday.com- Whether perineural invasion (PNI) identified in prostate cancer (CaP) biopsies is associated with disease recurrence is unclear from the literature. In an attempt to resolve this uncertainty, a systematic review was performed by Dr. Patricia Hamden and colleagues in the UK and published in the online edition of Cancer. What they found was that variable study design, execution and reporting excluded a definitive meta-analysis, but evidence suggests that PNI in biopsies was a significant prognostic indicator.

The authors' strategy used 128 search terms to identify articles published between 1990 and 2005. A total of 41,295 titles were reviewed by at least 2 reviewers and 128 articles identified for close evaluation. Ultimately, 10 surgical and 11 radiotherapy articles on PNI in biopsies as it related to patient outcomes were used in the report. Data items specific to biopsy PNI in CaP included biopsy procedure (amount of cores, number of nerves present and identification of PNI), histological slide preparation and pathological interpretation (consistency of identification, inclusion of information if no nerves were present).

No study reported on all data items and incomplete items ranged from 18% to 61% with a median of 39%. Exclusion criteria were variable, but included a history of prior treatment, unavailability of biopsies for review or the failure to obtain at least 4 biopsies. Only 1 surgical and 1 radiotherapy article was prospective. In surgical patients details on nerve sparing was generally lacking. In 12 studies, biopsies were reviewed for the presence of PNI and in 1 study 60% of biopsies were reviewed for this. In 5 studies the slides were not reviewed but the diagnosis was taken from the original report and in 3 articles the information was not provided. Only 2 articles reported blinded pathologic review. Individual patient data was sufficient in 5 articles to permit reanalysis.

The proportion of patients with PNI varied between 7% and 12% (median 9%) when the diagnosis was obtained form the original report and between 7% and 43% (median 23%) when slides were reviewed to identify PNI. Most studies had short (<6 months) of clinical follow-up. Overall, 6 of 10 surgical and 5 of 11 radiotherapy studies identified PNI as a prognostic factor in univariate analysis. Surgical articles that included a larger number of patients with less patient exclusion reported that PNI was independently prognostic in multivariate analysis with PSA and biopsy Gleason score. More than two-thirds of external radiotherapy studies but no brachytherapy study showed prognostic significance for perineural invasion. The highest incidence of PNI was found in locally-advanced disease.

Surprising to the authors were that none of the articles considered that the presence of nerves in the biopsies was a prerequisite for patient inclusion and no article provided data on the reproducibility of the PNI diagnosis. The authors conclude that the importance of PNI was likely to have been underestimated by the inclusion of uninformative test results (biopsies with no nerves in the specimens) and that despite this, the majority of studies including those performing multivariate analysis found prognostic significance to PNI. The weight of evidence supports PNI as of prognostic significance.

Patricia Harnden, Michael D. Shelley, Hayley Clements, Bernadette Coles, R. Sandy Tyndale-Biscoe, Brian Naylor, Malcolm D. Mason

Cancer 2006
Published Online: 22 Nov 2006

DOI: 10.1002/cncr.22388

Reviewed by UroToday.com Contributing Editor Christopher P. Evans, M.D.

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Copyright © 2006 - UroToday

Novel Regulation Of The Common Tumor Suppressor PTEN

PTEN is one of the most commonly mutated tumor suppressor genes. It is an antagonist for many cellular growth, proliferation and survival processes. When mutated or deleted, it causes cancers of the prostate, breast, colon, and brain. Researchers led by scientists at Memorial Sloan-Kettering Cancer Center have now identified fundamentally novel regulatory mechanisms of PTEN function. The findings from two related studies are published in the January 12 issue of Cell.

The first is research by Dr. Xuejen Jiang's laboratory at Sloan-Kettering which identified a novel component that regulates PTEN. This protein, NEDD4-1, controls protein stability in cells. Researchers found that NEDD4-1 is a key component in eliminating PTEN from cells by adding a molecular tag, ubiquitin, to PTEN causing degradation in the cellular machinery called proteasome. In a mouse model for prostate cancer, the researchers found that areas with aggressive tumor contained low PTEN levels and high NEDD4-1. They concluded that NEDD4-1 could promote cancer development by down-regulating PTEN.

The second study by Dr. Pier Paolo Pandolfi of Memorial Sloan-Kettering and colleagues found that the ubiquitination of PTEN by NEDD4-1 also regulates another important aspect of PTEN, its cellular localization.

PTEN has been found mostly in the cytoplasm but has been known to also be in cell nuclei. While the cytoplasmic function of PTEN is now quite well understood, its nuclear functions have been elusive. Looking at a family with an inherited PTEN mutation that caused them to have the cancer-susceptibility condition, Cowden Syndrome, researchers found that the patients' colon cancer strikingly lacked nuclear PTEN.

The Pandolfi and Jiang labs showed that the PTEN mutation in these patients prevented the addition of ubiquitin by NEDD4-1, providing a molecular mechanism for the detrimental effect of the mutant PTEN protein. They showed that the single ubiquitin tagging is necessary to import PTEN into the cell nucleus where it is protected from degradation and cancer is initiated.

According to the researchers, the uncovered key role of PTEN degradation provides a new therapeutic strategy. Since ubiquitination has both positive (single tag) and negative (repetitive tagging) effects, a class of drugs, the proteasome inhibitors, that selectively blocks the degrading effects of ubiquitination, should now be studied as possible treatments for cancers with PTEN mutations.

###

The research was supported by grants from The National Institutes of Health and the American Cancer Society.

Contact: Joanne Nicholas
Memorial Sloan-Kettering Cancer Center

Call For Better Prostate Cancer Biopsies

Routine collection of additional information from prostate cancer biopsies could allow better decisions about the best choice of treatment, according to a study published in the journal Cancer*.

Through a systematic review of the published evidence, scientists funded by the NHS Cancer Screening Programme, Cancer Research UK and Cancer Research Wales found evidence of a link between the spread of cancer to nerves in the prostate gland - called 'perineural invasion' or PNI - and a poorer outlook for prostate cancer patients.

The clinical significance of PNI has been unclear, and therefore current guidelines for pathologists make no mention of PNI, leaving it up to individual doctors to decide whether they check for it or not.

This review shows a significant association between PNI and the risk of disease recurrence but the risk associated with PNI remains impossible to fully quantify from the few studies that have been done so far. The researchers are recommending to the Royal College of Pathologists that PNI should be assessed in every case of prostate cancer. This would help determine more precisely the size of the associated risk and so aid future decisions about treatment.

Prostate cancer is the most common cancer in men, with more than 32,000 cases diagnosed each year in the UK, but the best approach to treatment is not always clear. Doctors currently have very little evidence to rely on when deciding on the most appropriate treatment option.

Widespread use in the US of the PSA (Prostate-Specific Antigen) test to identify asymptomatic prostate cancer has led to an increase in the number of prostate tumours detected, but the PSA test gives only limited information regarding a patient's prognosis.

The best management of early diagnosed tumours is particularly hard to judge. Options include radical prostatectomy - surgical removal of the prostate - and active surveillance or so-called 'watchful waiting', which may be chosen on the basis that most prostate tumours are slow-growing and occur in elderly men in whom prostate cancer will not be their cause of death. If, however, the cancer turns out to be growing faster, then active treatment is offered.

Cancer Research UK's Dr Patricia Harnden, lead author of the report, said: "We've shown that PNI increases the risk of recurrence in prostate cancer. If it is found in a prostate biopsy, it could mean the difference between choosing 'watchful waiting' and immediately treating the cancer, or perhaps giving a longer course of therapy. Pathology is not being used to its full potential in prostate cancer if PNI is not looked for.

" Making PNI a mandatory reporting item in the guidelines of the Royal College of Pathologists would have two effects - it would help gather more data on the exact association between PNI and risk of recurrence, and it would enable doctors to make more informed decisions on how best to treat their patients. We must also ensure that future studies of pathological prognostic factors such as PNI are designed well enough to properly assess their significance."

Julietta Patnick, director of NHS Cancer Screening Programmes, said: "I am very pleased that the NHS Cancer Screening Programmes has been able to facilitate this significant work. The results of this review will assist health professionals in making the best treatment decisions for patients."

Professor John Toy, medical director of Cancer Research UK, said: "Some prostate cancer patients have normal PSA levels, and some healthy men have high PSA levels that are not caused by cancer. It can often be extremely difficult to predict with certainty the prognosis for many men with early prostate cancer.

"Therefore, the identification of a prognostic marker that indicates an aggressive cancer would be of great value. PNI in a prostate biopsy may be such a marker. We must ensure that no opportunity to gather potentially important information about prostate cancer is wasted."

Professor Adrian Newland, president of the Royal College of Pathologists, said: "The Royal College of Pathologists welcomes this systematic review of PNI in prostatic cancer biopsies, particularly the identification of PNI as a reliable predictor of adverse clinical outcome.

"Detailed histological evaluation by medically-trained histopathologists is essential in the assessment of cancer specimens, particularly the identification of features of clinical value to patients and their supervising clinicians alike. The Royal College of Pathologists endorses the view expressed in the paper that well designed studies using pre-defined stringent protocols are now required to provide robust objective estimates of risk, following identification of PNI in prostatic core biopsies, as an aid in the planning of treatment for men diagnosed with prostate cancer."

* Harnden et al. (2007) "The prognostic significance of perineural invasion in prostatic cancer biopsies: A systematic review" CANCER; Vol. 109 Issue 1, pp13-24

For more statistics on prostate cancer, please visit Cancer Research UK's CancerStats website.

The NHS Prostate Cancer Risk Management programme

-- Information on Prostate Cancer Risk Management, prostate cancer and the PSA test is available here.

-- For more information about the NHS Cancer Screening Programmes, contact Andrea Whitfield, Caroline Greenaway, Sarah Gibbs or Helen Ketton in the press office on 020 7025 7510 or email screening@westminster.com

About Cancer Research UK

Together with its partners and supporters, Cancer Research UK's vision is to beat cancer.

-- Cancer Research UK carries out world-class research to improve understanding of the disease and find out how to prevent, diagnose and treat different kinds of cancer.

-- Cancer Research UK ensures that its findings are used to improve the lives of all cancer patients.

-- Cancer Research UK helps people to understand cancer, the progress that is being made and the choices each person can make.

-- Cancer Research UK works in partnership with others to achieve the greatest impact in the global fight against cancer.

http://www.cancerresearchuk.org

Watson Announces Positive Phase 3 Study Results On Silodosin For Treatment Of Benign Prostatic Hyperplasia

Watson Pharmaceuticals, Inc. (NYSE: WPI), a leading specialty pharmaceutical company, today announced positive top-line data from two Phase 3 studies of silodosin, the Company's investigational drug being studied for the treatment of signs and symptoms of benign prostatic hyperplasia (BPH).

The primary objective of the trials was to demonstrate that 8mg silodosin given once daily for 12 weeks was superior to placebo for the relief of BPH symptoms, including both obstructive and irritative symptoms, as measured by a baseline-to-endpoint change in the total score of the International Prostate Symptom Score-1 (IPSS-1). Secondary endpoints included improvements in maximum urine flow (Qmax). Very rapid and statistically significant improvements were seen in both of these endpoints.

Silodosin was well tolerated in both studies. Cardiovascular and blood pressure related side effects, including dizziness and orthostasis, were low in both trials. As expected with highly uroselective alpha blockers, ejaculations with little or no semen were the most commonly reported side effect seen in the trials. The vast majority of these reports were mild to moderate in intensity and patient withdrawal from the trial was low.

Results from these studies will be submitted for presentation at a medical meeting at a later date.

"We are extremely encouraged with the efficacy that was demonstrated in these trials, supporting the potential clinical utility of silodosin in treating BPH," said Dr. Charles Ebert, Watson's Senior Vice President, Research and Development. "Our ongoing one year safety study remains on track to be completed this fall and we expect to submit a New Drug Application to FDA in the first half of 2008."

"The completion of the silodosin Phase 3 studies is an important milestone for Watson," continued Dr. Ebert. "As BPH is one of the most commonly treated disorders by urologists, silodosin is expected to greatly enhance our growing urology franchise."

Benign Prostatic Hyperplasia (BPH)

BPH is characterized by a non-cancerous enlarged prostate that leads to obstructive and irritative urinary symptoms. In the United States (US) BPH affects more than half of men in their sixties and as many as 90 percent of men by the age of 85. Additionally, approximately $1.7 billion is spent annually on BPH prescription drug treatment.

Silodosin

Silodosin is a novel, highly uroselective alpha (1A)-adrenoceptor antagonist originally developed by Kissei Pharmaceutical Co., Ltd. in Japan and licensed to Watson for the US, Canada and Mexico markets. Silodosin preferentially binds to the alpha (1A) receptors in the prostate and bladder neck relative to cardiovascular associated receptors, thereby maximizing target organ activity while minimizing the potential for blood pressure effects. Urief(R) (silodosin) 4mg, dosed twice daily, was launched in Japan in May 2006 and is marketed in cooperation with Daiichi Pharmaceutical Co., Ltd.

About Watson Pharmaceuticals, Inc.

Watson Pharmaceuticals, Inc., headquartered in Corona, California, is a leading specialty pharmaceutical company that develops, manufactures, markets, sells and distributes brand and generic pharmaceutical products. Watson pursues a growth strategy combining internal product development, strategic alliances and collaborations and synergistic acquisitions of products and businesses.

For press releases and other company information, visit Watson Pharmaceuticals' Web site at http://www.watsonpharm.com.

About Kissei Pharmaceutical Co., Ltd.

Kissei Pharmaceutical Co., Ltd., headquartered in Matsumoto, Nagano prefecture, founded in 1946, is a Japanese pharmaceutical company that develops, manufactures, markets, sells and distributes brand pharmaceutical products. Kissei is primarily focused on three important fields of new drug research: urogenital, endocrinology & metabolism and immunology & allergy.

Forward-Looking Statement

Any statements contained in this press release that refer to future events or other non-historical facts are forward-looking statements that reflect Watson's current perspective of existing trends and information as of the date of this release. Except as expressly required by law, Watson disclaims any intent or obligation to update these forward-looking statements. Actual results may differ materially from Watson's current expectations depending upon a number of factors affecting Watson's business. These factors include, among others, the difficulty of predicting the timing or outcome of clinical studies, product development efforts and FDA or other regulatory agency approvals or actions; whether the results of clinical trials for silodosin and other information will be sufficient to support approval of silodosin by FDA and other regulatory authorities; delays regarding the regulatory approval process, including the timing and scope of approval received, if any; market acceptance and continued demand for Watson's products, including silodosin, if approved; patents and other intellectual property rights held by competitors and other third parties; successful compliance with FDA and other governmental regulations applicable to Watson's products and/or business; and such other risks and uncertainties detailed in Watson's periodic public filings with the Securities and Exchange Commission, including but not limited to Watson's Annual Report on Form 10-K for the year ended December 31, 2005 and its Quarterly Report on Form 10-Q for the quarter ended September 30, 2006.

Watson Pharmaceuticals, Inc.
http://www.watsonpharm.com

Dendreon's PROVENGE Granted FDA Priority Review For The Treatment Of Asymptomatic, Metastatic, Androgen-Independent Prostate Cancer

Dendreon Corporation (Nasdaq: DNDN) today announced that the U.S. Food and Drug Administration (FDA) has accepted for filing and has assigned priority review status to the Company's Biologics License Application (BLA) for PROVENGE(R) (sipuleucel-T), its investigational active cellular immunotherapy for the treatment of asymptomatic, metastatic, androgen-independent (also known as hormone refractory) prostate cancer.

Priority Review is granted to products that, if approved, would provide a significant improvement in the safety or effectiveness of the treatment, diagnosis or prevention of a serious or life-threatening disease. The goal for reviewing a product with Priority Review status is six months from the filing date. The Prescription Drug User Fee Act (PDUFA) date for completion of review by the FDA of the PROVENGE BLA is May 15, 2007.

"Clinical trials have shown that PROVENGE increases survival and is generally well tolerated in men with late-stage prostate cancer, a highly prevalent disease for which there are currently few available treatment options," said Mitchell H. Gold, president and chief executive officer of Dendreon. "We are extremely pleased the FDA has granted priority review to PROVENGE, which may represent an important new treatment option for men suffering from prostate cancer."

Prostate cancer is the most common non-skin cancer in the United States and the third most common cancer worldwide. More than one million men in the United States have prostate cancer, with an estimated 232,000 new cases of prostate cancer diagnosed each year. More than 30,000 men die each year of the disease.

The BLA submission is based primarily on an improvement in overall survival observed in Study D9901, a multi-center, randomized, double-blind, placebo-controlled Phase 3 Study, the results of which were published in the July issue of the Journal of Clinical Oncology.

About PROVENGE

PROVENGE (sipuleucel-T) is an investigational product that may represent the first in a new class of active cellular immunotherapies (ACIs) that are uniquely designed to stimulate a patient's own immune system. PROVENGE is in late-stage clinical development for the treatment of patients with advanced prostate cancer. In clinical studies, patients typically received three infusions over a one-month period as a complete course of therapy.

About Dendreon

Dendreon Corporation is a biotechnology company whose mission is to target cancer and transform lives through the discovery, development and commercialization of novel therapeutics that harness the immune system to fight cancer. The Company applies its expertise in antigen identification, engineering and cell processing to produce active cellular immunotherapy product candidates designed to stimulate an immune response. Active cellular immunotherapy holds promise because it may provide patients with a meaningful clinical benefit, such as survival, combined with low toxicity. The Company has headquarters in Seattle and is traded on the Nasdaq Global Market under the symbol DNDN. For more information about the Company and its programs, visit http://www.dendreon.com.

Except for historical information contained herein, this news release contains forward-looking statements that are subject to risks and uncertainties surrounding the efficacy of PROVENGE to treat men suffering from prostate cancer, risks and uncertainties surrounding the presentation of data to the FDA and approval of product applications by the FDA and risks and uncertainties inherent in the process of discovering, developing and commercializing drugs that are safe and effective for use as human therapeutics. Factors that may cause such differences include risks related to our limited operating history, risks associated with completing our clinical trials, the risk that the safety and/or efficacy results of a clinical trial for PROVENGE will not support an application for a biologics license, the risk that the FDA may interpret data differently than we do or require more data or a more rigorous analysis of data than expected, the risk that the FDA will not approve a product for which a biologics license has been applied, the risk that the results of a clinical trial for PROVENGE or other product may not be indicative of results obtained in a later clinical trial, risks that we may lack the financial resources and access to capital to fund required clinical trials or commercialization of PROVENGE, our dependence on the efforts of third parties, and our dependence on intellectual property. Further information on the factors and risks that could affect Dendreon's business, financial condition and results of operations are contained in Dendreon's public disclosure filings with the U.S. Securities and Exchange Commission, which are available at http://www.sec.gov.

Dendreon Corporation
http://www.dendreon.com

Tomato-Broccoli Combo Shown To Be Effective In Shrinking Prostate Tumours

A new University of Illinois study shows that tomatoes and broccoli--two vegetables known for their cancer-fighting qualities--are better at shrinking prostate tumors when both are part of the daily diet than when they're eaten alone.

"When tomatoes and broccoli are eaten together, we see an additive effect. We think it's because different bioactive compounds in each food work on different anti-cancer pathways," said University of Illinois food science and human nutrition professor John Erdman.

In a study published in the January 15 issue of Cancer Research, Erdman and doctoral candidate Kirstie Canene-Adams fed a diet containing 10 percent tomato powder and 10 percent broccoli powder to laboratory rats that had been implanted with prostate cancer cells. The powders were made from whole foods so the effects of eating the entire vegetable could be compared with consuming individual parts of them as a nutritional supplement.

Other rats in the study received either tomato or broccoli powder alone; or a supplemental dose of lycopene, the red pigment in tomatoes thought to be the effective cancer-preventive agent in tomatoes; or finasteride, a drug prescribed for men with enlarged prostates. Another group of rats was castrated.

After 22 weeks, the tumors were weighed. The tomato/broccoli combo outperformed all other diets in shrinking prostate tumors. Biopsies of tumors were evaluated at The Ohio State University, confirming that tumor cells in the tomato/broccoli-fed rats were not proliferating as rapidly. The only treatment that approached the tomato/broccoli diet's level of effectiveness was castration, said Erdman.

"As nutritionists, it was very exciting to compare this drastic surgery to diet and see that tumor reduction was similar. Older men with slow-growing prostate cancer who have chosen watchful waiting over chemotherapy and radiation should seriously consider altering their diets to include more tomatoes and broccoli," said Canene-Adams.

How much tomato and broccoli should a 55-year-old man concerned about prostate health eat in order to receive these benefits? The scientists did some conversions.

"To get these effects, men should consume daily 1.4 cups of raw broccoli and 2.5 cups of fresh tomato, or 1 cup of tomato sauce, or ВЅ cup of tomato paste. I think it's very doable for a man to eat a cup and a half of broccoli per day or put broccoli on a pizza with ВЅ cup of tomato paste," said Canene-Adams.

Erdman said the study showed that eating whole foods is better than consuming their components. "It's better to eat tomatoes than to take a lycopene supplement," he said. "And cooked tomatoes may be better than raw tomatoes. Chopping and heating make the cancer-fighting constituents of tomatoes and broccoli more bioavailable."

"When tomatoes are cooked, for example, the water is removed and the healthful parts become more concentrated. That doesn't mean you should stay away from fresh produce. The lesson here, I think, is to eat a variety of fruits and vegetables prepared in a variety of ways," Canene-Adams added.

Another recent Erdman study shows that rats fed the tomato carotenoids phytofluene, lycopene, or a diet containing 10 percent tomato powder for four days had significantly reduced testosterone levels. "Most prostate cancer is hormone-sensitive, and reducing testosterone levels may be another way that eating tomatoes reduces prostate cancer growth," Erdman said.

Erdman said the tomato/broccoli study was a natural to be carried out at Illinois because of the pioneering work his colleague Elizabeth Jeffery has done on the cancer-fighting agents found in broccoli and other cruciferous vegetables. Jeffery has discovered sulfur compounds in broccoli that enhance certain enzymes in the human body, which then act to degrade carcinogens.

"For ten years, I've been learning how the phytochemicals in tomatoes affect the progression of prostate cancer. Meanwhile Dr. Jeffery has been investigating the ways in which the healthful effects of broccoli are produced. Teaming up to see how these vegetables worked together just made sense and certainly contributes to our knowledge about dietary treatments for prostate cancer," said Erdman.

###

Authors of the tomato/broccoli study are Kirstie Canene-Adams, Brian L. Lindshield, Elizabeth H. Jeffery, and John W. Erdman Jr. at the University of Illinois and Shihua Wang and Steven K. Clinton of The Ohio State University. The study was funded by the American Institute for Cancer Research and the U.S. Department of Agriculture.

The U of I study of the effects of tomato carotenoids on serum testosterone was published in the December 2006 issue of the Journal of Nutrition. Authors are Jessica K. Campbell, Chad K. Stroud, Manabu T. Nakamura, Mary Ann Lila, and John W. Erdman Jr. Funding was provided by the National Institutes of Health's National Cancer Institute.

Contact: Phyllis Picklesimer
University of Illinois at Urbana-Champaign

Prostate Cancer Detection And Screening Session I - AUA 2006

UroToday.com - A Podium Session on Prostate Cancer Detection and Screening took place on Sunday May 21, 2006 at the annual AUA meeting in Atlanta. Some highlights from the 12 papers presented are as follows.

Dr. Ian Thompson, San Antonio, TX reported on ability for PSA to detect CaP in finasteride treated patients. Patients in the PCPT study who were on placebo or finasteride and underwent prostate biopsy were evaluated. Receiver operator characteristic curves (ROC) were calculated for the presence and absence of CaP and Gleason score. Of the 5,112 men in the placebo group, 1,111 were diagnosed with CaP compared to 695 of 4,579 men in the finasteride group. The area under the ROC curve was greater for finasteride than placebo. This was true for cancer detection overall and for high-grade disease. This study suggests a bias toward increased detection of CaP and high-grade CaP in men treated with finasteride in the PCPT study.

Dr. Loeb, Washington, DC stated that a PSA velocity (PSAV) of 0.5ng/ml/year should be used in men under age 60. Using the database of Dr. Catalona, 6,844 men under age 60 were identified and 346 of these were diagnosed with CaP. Analysis of their PSAV showed that a PSAV >0.5ng/ml/year was more predictive of CaP than age, total PSA, family history or race. Even those men with a PSA <0.25ng/ml had similar results. The sensitivity, specificity and positive and negative predictive values were 62%, 85%, 18%, and 98%, respectively.

Dr. Georg Bartsch, Innsbruck Austria and colleagues in several other countries presented an update on the Tyrolean CaP screening study. The program using PSA has been in place since 1993. Men diagnosed with CaP could go on to radical prostatectomy. Migration to lower stage of CaP and an increase in the number of organ-confined tumors was observed since the start of the program. A reduction in the mortality rates was observed in Tyrol and the rest of Austria (where PSA screening was not introduced). Dr. Bartsch concluded that the decline in death is likely a result of downstaging through surgical curable disease and successful treatment.

A presentation from Dr. Alschibaja, Munich Germany suggests that clinically insignificant CaP cannot be reliably predicted. A cohort of 349 patients undergoing radical prostatectomy had pathology specimens analyzed. Of these, 38 (9.2%) met the criteria for insignificant CaP. The model generated had a sensitivity of 84.2% and a specificity of 90.4%. The positive predictive value was only 51.5%, suggesting that 9.4% of clinically significant tumors would be missed.

By Christopher P. Evans, M.D.

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:
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Copyright © 2006 - UroToday

Prostate Cancer Basic Research Session II - AUA 2006

UroToday.com - A Discussed Poster Session on Prostate Cancer Basic Research took place on Sunday May 21, 2006 at the annual AUA meeting in Atlanta. A few of the many interesting posters on basic and potential translation science are described herein.

Dr. Davis Syme, Melbourne, Australia reported the effect of castration on cavernous nerve graft regeneration. Rats underwent bilateral cavernous nerve neurotomy followed by unilateral interpositional nerve graft using the genitofemoral nerve. Animals were then randomized to undergo castration, remain hormonally intact or receive testosterone. Electrostimulation of the nerve grafts was performed at 3 months and histologic analysis performed. Castration resulted in a significant reduction to electrostimulation and clinical application suggests that nerve grafts would be of little use in patients who may need androgen deprivation following surgery.

Dr. Christopher Evans, UC Davis presented work in a chimeric animal tumor model. His laboratory demonstrated that neuropeptide overexpressing androgen-insensitive CaP cells supported the growth and migration of androgen-sensitive CaP cells in androgen-deprived in vitro and in vivo environments. They have also shown that CaP cells express neuropeptides at the time of androgen-withdrawal. Taken together, this suggests that at the time of castration, some androgen-sensitive CaP cells may escape cell death due to paracrine support from surrounding neuropeptide expressing CaP cells.

Dr. Deka from Northwestern University reported that variants in the HEPSIN gene are associated with CaP in Caucasian men. The HEPSIN gene is located on chromosome 9q and codes for a transmembrane cell surface serine protease that is over-expressed in CaP. A comparison was made between 604 men with CaP and 576 controls, all Caucasian. Five of 11 single nucleotide polymorphisms on the HEPSIN gene were found to have significant differences in allele frequencies between the groups. This suggests an association between genetic variants in HEPSIN and CaP carcinogenesis in Caucasian men.

Dr. Wu from the laboratory of Dr. Dan Theodorescu, University of Virginia reported on the tumor suppressor gene PTEN and its effect on CaP cell migration in the bone microenvironment. PTEN was expressed in a PTEN-null CaP cell line, C4-2. The PTEN cells selectively migrated towards proteins expressed by bone calavaria compared to proteins expressed by lung fibroblast cells. Compared to control cells, the PTEN cells did not show increased proliferation, suggesting that the effect is purely on migration and not due to enhanced growth. Further experiments identified the PTEN mechanism as mediated through the small GTPase Rac1.

By Christopher P. Evans, M.D.

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:
http://www.urotoday.com

Copyright © 2006 - UroToday

Prostate Cancer Basic Research Session I - AUA 2006

UroToday.com - A Discussed Poster Session on Prostate Cancer Basic Research took place on Sunday May 21, 2006 at the annual AUA meeting in Atlanta. Many interesting posters on basic and potential translation science were presented. A few of these are described herein.

Dr. Stephen Freedland and colleagues, Baltimore MD compared gene expression patterns by microarray from obese and normal weight men. They found differences greater than expected by chance alone. 3-hydroxymethyl glutaryl coA, a rate limiting enzyme in ketone body production was significantly lower in obese men.

Dr. Eric Klein, Cleveland Clinic presented their work on a virus closely related to murine leukemia viruses that were identified in prostate tumors of men homozygous for the R462Q mutation in the HPC1 gene. This work suggests that there may be a link between viral infection and the development of CaP in men with a mutated gene.

A research group from Japan and California had their work on a biomarker in different ethnic cohorts presented by Dr. Enokida. They found that GSTP-1 gene hypermethylation was a biomarker for CaP in African-American as opposed to Caucasian or Asian men, but that it strongly influenced tumor progression in Asian men with CaP.

Dr. Ralf Herwig presented exciting work from Austrian collaborators regarding a new method to differentiate between benign and malignant prostate disease. To do this, they isolated peripheral blood mononuclear cells from 25 men with CaP and 10 healthy controls. Using cell surface antigens, the cells populations were separated by flow cytometry and intracellular PSA measured. Differentiation between malignant and benign disease was achieved using the CD14/PSA staining. PSA was only found in activated CD14 cells, and was much higher in metastatic compared to localized CaP.

Dr. Mark Rubin's group from Boston, MA characterized Metastasis-Associated Protein 1 (MTA1) in CaP cell lines. MTA-1 is overexpressed in several tumor types and facilitates cancer through transcription repression. MTA-1 overexpression in LNCaP cells resulted in significantly increased ability for migration and invasion. MTA-1 overexpression resulted in upregulation of several genes associated with CaP progression.

Work from Vancouver, Canada presented by Dr. Hayashi discussed how the anti-apoptotic survival gene Clusterin upregulates the transcription factor NFk-B. Androgen-withdrawal is shown to up-regulate Clusterin expression. Using microarray techniques combined with small interfering RNA inhibition experiments NFk-B was identified to be under Clusterin regulation. This suggests that the NFk-B pathway may be a potential downstream effector of clusterin-mediated cytoprotective function.

By Christopher P. Evans, M.D.

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:
http://www.urotoday.com

Copyright © 2006 - UroToday

Johns Hopkins Researchers Present Advances In Prostate Cancer Program At The Annual Meeting Of The American Urological Association

Ciphergen Biosystems, Inc. (Nasdaq: CIPH) announced the discovery of two biomarkers that may aid in the management of prostate cancer, including for the detection, staging, and prediction of recurrence. These markers, a fragment of protein C inhibitor (PCI) and complement factor 4 (C4a), were identified in two separate studies, a multi-institutional study encompassing over 400 men and a five-year longitudinal study following 104 patients after radical prostatectomy. These studies demonstrated that PCI provides information useful for the detection and staging of prostate cancer, and the combined use of pre-surgery PCI, PSA, and C4a is predictive of prostate cancer recurrence. The work was performed by Dr. Daniel Chan and Dr. Zhen Zhang of the Johns Hopkins Medical Institutions as part of our research collaboration.

"We are pleased with the progress of our ongoing collaborative prostate cancer program with Johns Hopkins. These findings address a critical aspect of the management of prostate cancer, as the ability to predict recurrence can help physicians and patients understand better the aggressiveness of disease," said Gail S. Page, President and CEO of Ciphergen. "The discovery of PCI using Ciphergen's technology demonstrates its ability to identify markers directly related to the disease process, since PCI is present in seminal fluid and directly interacts with PSA. Further validation is underway."

About Ciphergen

Ciphergen is dedicated to translating protein biomarkers and panels of biomarkers into protein molecular diagnostic tests that improve patient care. We are also focused on providing collaborative R&D services through our Biomarker Discovery Center(R) laboratories for biomarker discovery for new diagnostic tests as well as pharmacoproteomic services for improved drug toxicology, efficacy and theranostic assays. Ciphergen develops, manufactures and markets a family of ProteinChip(R) Systems and services for clinical, research and process proteomics applications. ProteinChip Systems enable protein discovery, validation, identification and assay development to provide researchers with predictive, multi-marker assay capabilities and a better understanding of biological function at the protein level. Additional information about Ciphergen can be found at http://www.ciphergen.com.

Safe Harbor Statement

Note Regarding Forward-Looking Statements: This press release contains forward-looking statements. For purposes of the Private Securities Litigation Reform Act of 1995 (the "Act"), Ciphergen disclaims any intent or obligation to update these forward-looking statements, and claims the protection of the Safe Harbor for forward-looking statements contained in the Act. Examples of such forward-looking statements include statements regarding the usefulness of certain biomarkers to predict the recurrence of disease and the ability of Ciphergen to use such biomarkers in the creation of diagnostic tests. Actual results may differ materially from those projected in such forward-looking statements due to various factors, including the risk that Ciphergen may not be able to develop diagnostic tests based on the discoveries of certain biomarkers. Investors should consult Ciphergen's filings with the Securities and Exchange Commission, including its Form 10-K filed March 17, 2006, for further information regarding these and other risks related to the Company's business. Ciphergen, ProteinChip and Biomarker Discovery Center are registered trademarks of Ciphergen Biosystems, Inc.

Ciphergen Biosystems, Inc.
http://www.ciphergen.com/

Phase II Trial Of Trovax(R) In Prostate Cancer Commences - Oxford BioMedica

Oxford BioMedica (LSE: OXB), a leading gene therapy company, announced today that a Phase II trial of TroVax in patients with prostate cancer that is unresponsive to hormone therapy is open for recruitment. This is the first clinical trial of TroVax in this cancer type.

The Phase II trial in prostate cancer is being conducted at the Methodist Hospital in Houston, Texas, USA. The Principal Investigator for the trial is Dr Robert Amato. The trial is designed to enrol 24 men with hormone-refractory prostate cancer who have previously received chemotherapy or have refused chemotherapy and have progressive disease. The trial is open label and will have two arms (12 patients each) to assess the activity of TroVax alone versus TroVax alongside an approved treatment for prostate cancer, granulocyte macrophage-colony stimulating factor (GM-CSF).

The primary objectives of the trial are to evaluate the safety and synergies of the combination treatment, and to assess whether GM-CSF, which is known to increase white blood cell count and hence boost the immune system, increases the anti-cancer immune response stimulated by TroVax. Efficacy endpoints include objective response rate, progression-free survival, overall survival and changes in prostate-specific antigen (PSA) level, which is a recognised marker of disease status.

Prostate cancer is the leading cause of cancer in men. Localised radiotherapy or surgery is potentially curative for early-stage disease although many patients relapse and require hormone therapy. However, therapeutic options are limited when the cancer has progressed and no longer responds to hormone therapy, which is the setting for the Phase II trial of TroVax. Initial data from this trial are expected in the first half of 2007. According to Datamonitor, treatments for prostate cancer generated worldwide sales of $2.7 billion in 2004.

Commenting on the start of the Phase II trial in prostate cancer, Oxford BioMedica's Chief Medical Officer, Dr Mike McDonald, said: "We are delighted that Dr Amato is supporting a Phase II trial of TroVax in prostate cancer. Given what we know of the product's safety profile and the anti-cancer immune response that it stimulates, we are hopeful that TroVax can provide a new therapeutic option for patients with prostate cancer who have progressed despite hormone therapy and for whom there are few available treatments."

Dr Robert Amato, Director of the Genitourinary Oncology Center at the Methodist Hospital said: "TroVax could provide a significant benefit to patients with hormone-refractory prostate cancer, particularly when administered with an effective immunostimulant such as GM-CSF. Our team at the Methodist Hospital has seen some intriguing clinical responses with TroVax from our trial in renal cell carcinoma and we are delighted to expand our collaboration with Oxford BioMedica into prostate cancer."

Oxford BioMedica's Chief Executive Officer, Professor Alan Kingsman added: "As we broaden and deepen the clinical development of TroVax, the value of our lead product candidate increases for potential partners."

Clinical evaluation of TroVax is ongoing in renal cell carcinoma, colorectal cancer and now prostate cancer. Oxford BioMedica plans to start a Phase III trial in renal cell carcinoma in the second half of 2006. The Company recently secured a Special Protocol Assessment agreement with the FDA for this Phase III trial. An update on the clinical trials and development plan for TroVax will be released to coincide with TroVax presentations at the American Society of Clinical Oncology (ASCO) Annual Meeting, to be held on 2-6 June in Atlanta, Georgia, USA.

Oxford BioMedica plc

Oxford BioMedica (LSE: OXB) is a biopharmaceutical company specialising in the development of novel gene-based therapeutics with a focus on the areas of oncology and neurotherapy. The Company was established in 1995 as a spin out from Oxford University, and is listed on the London Stock Exchange.

Oxford BioMedica has core expertise in gene delivery, as well as in-house clinical, regulatory and manufacturing know-how. In oncology, the pipeline includes an immunotherapy and a gene therapy in multiple Phase II trials, and a preclinical targeted antibody therapy in collaboration with Wyeth. In neurotherapy, the Company's lead product is a gene therapy for Parkinson's disease, which is expected to enter clinical trials in 2006, and four further preclinical candidates. The Company is underpinned by over 80 patent families, which represent one of the broadest patent estates in the field.

The Company has a staff of approximately 70 split between its main facilities in Oxford and its wholly owned subsidiary, BioMedica Inc, in San Diego, California. Oxford BioMedica has corporate collaborations with Wyeth, Intervet, Sigma-Aldrich, Viragen, MolMed, Virxsys and Kiadis; and has licensed technology to a number of companies including Merck & Co, Biogen Idec and Pfizer.

TroVax(R)

TroVax is Oxford BioMedica's leading cancer immunotherapy product. It is designed specifically to stimulate an anti-cancer immune response and has potential application in most solid tumour types. TroVax targets the tumour antigen 5T4, which is broadly distributed throughout a wide range of solid tumours. The presence of 5T4 is correlated with poor prognosis. The product consists of a poxvirus (MVA) gene transfer system, which delivers the gene for 5T4 and stimulates a patient's body to produce an anti-5T4 immune response. This immune response destroys tumour cells carrying the 5T4. TroVax has attracted external support from Cancer Research UK and the US National Cancer Institute. Over 100 patients have now been treated with TroVax in six clinical trials (collectively over 400 doses). The Company is targeting colorectal cancer and renal cell carcinoma (RCC) as lead indications for the development of TroVax. Renal cell carcinoma is an indication where TroVax might achieve a rapid route to product registration.

Prostate cancer

Prostate cancer is the leading cause of cancer in men. According to the American Cancer Society, an estimated 232,090 new cases of prostate cancer were diagnosed in the USA in 2005 and approximately 29,900 men die of this disease annually. The five-year survival rate of men with prostate cancer is 98%, although this falls to 34% for metastatic disease. Localised radiotherapy or surgery is potentially curative for early-stage disease although many patients relapse and require hormone therapy. According to Datamonitor, treatments for prostate cancer generated worldwide sales of $2.7 billion in 2004. However, therapeutic options are limited when the cancer has progressed and no longer responds to hormone therapy. Early detection is important, and it is recommended that men over the age of 50 have a prostate-specific antigen (PSA) blood test every year.

http://www.oxfordbiomedica.co.uk