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

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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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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

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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

Panacea Pharmaceuticals Initiates Pivotal, Prospective Multi-Center Study To Evaluate The Diagnostic Performance Of PC Detect(SM) For Prostate Cancer

Panacea Pharmaceuticals, Inc. announced the initiation of the pivotal, prospective multi-center clinical study to evaluate the diagnostic performance of PC Detect(SM), the Company's prostate cancer screening test. Patients are currently being enrolled in this study at 15 sites in the U.S. to demonstrate that the performance of PC Detect(SM), a simple blood test, will serve as an aid in the detection of prostate cancer in men 50 years and older who are referred for biopsy because of a tPSA > 4.0 ng/mL and/or an abnormal digital rectal exam. The addition of PC Detect(SM) to the current screening methods should reduce the number of men recommended to undergo prostate biopsies and subsequently found to be cancer- free. PC Detect(SM) will soon be available from Panacea Laboratories (http://www.panacea-labs.com), a division of Panacea Pharmaceuticals, which is fully compliant with the requirements of the Clinical Laboratory Improvement Amendments of 1988 (CLIA). The Company anticipates submission of a Pre-Market Application (PMA) to the U.S. Food and Drug Administration later in 2007 to facilitate development of a PC Detect(SM) kit, which will be commercialized through clinical laboratories around the country.

Prostate cancer is currently the most prevalent form of cancer in men and the second leading cause of male cancer death in the United States. The major screening tools for prostate cancer used by physicians to determine whether to refer a patient for a prostate biopsy are the prostate-specific antigen (PSA) and the digital rectal examination (DRE). The American Cancer Society (ACS) recommends a PSA blood test and DRE yearly, beginning at age 50. However, some controversy exists as to the utility and predictive validity of PSA for prostate cancer. PSA is a tissue-specific protein and has been shown to be elevated in both benign prostate conditions as well as prostate cancer. According to the ACS, patients with a PSA > 10 ng/mL are recommended to have a biopsy since >50% of these men have been found to have biopsies positive for cancer. A biopsy may be recommended for a non-suspicious DRE result and a PSA result of between 4-10 ng/mL as 25% of these men will also be positive for prostate cancer. DRE has a reported sensitivity of 55%-68% in asymptomatic men, but values as low as 18%-22% have been reported. The reported positive predictive value of DRE is 6%-33%. A cutoff value of a PSA 4.0 ng/mL at base- line has been found to have a sensitivity of 46% with respect to the identification of cases of prostate cancer that would occur within the next 10 years. The reported positive predictive value of PSA in asymptomatic men is 28%-35%.

PC Detect(SM), a CLIA laboratory service, is a new method for screening a patient's serum with a simple blood draw to help determine the likelihood that prostate cancer is present. PC Detect(SM) is recommended for men who have an elevated PSA and/or an abnormal DRE. PC Detect(SM) provides information to differentiate prostate cancer from benign conditions, and to help guide both the physician and patient regarding further diagnostic testing and management. Human Aspartyl (Asparaginyl) Beta-Hydroxylase (HAAH) is a cancer biomarker. HAAH has been established as an excellent biomarker for many cancer diagnoses based upon its biochemical/cellular properties and its known biological function. The protein is undetectable in sera from cancer-free individuals; thus, an elevated serum protein level of HAAH is highly diagnostic for cancer. Low/undetectable levels of HAAH, when measured with PC Detect(SM), may obviate the need for a prostate biopsy, despite a slightly elevated PSA. Thereby, a patient could avoid an unnecessary biopsy with its associated morbidity and cost.

"PC Detect(SM), in combination with PSA and DRE, should significantly enhance our ability to identify men with a high likelihood of having prostate cancer as compared to screening with PSA and DRE alone," commented Neal Shore, MD, of the Carolina Urologic Research Center and Grand Strand Urology, Myrtle Beach, South Carolina, who serves as Principal Investigator for the study. "As a practicing urologist, I look forward to using PC Detect(SM) to enhance the quality of care for my patients and reduce the number of unnecessary prostate biopsies."

"Initiation of the pivotal PC Detect(SM) marks a significant milestone for Panacea. This test should improve the physician's ability to identify men with a high likelihood of having prostate cancer, and avoid biopsies for those with a negligible risk of cancer," observed Stephen N. Keith, MD, MSPH, President and Chief Operating Officer at Panacea. "The addition of PC Detect(SM) to the list of diagnostic tests offered by Panacea Laboratories; and the FDA approval of this test and subsequent development of a kit, provide further evidence that Panacea is a leading research, product development and commercial life science company."

About Panacea's Oncology Platform

Panacea is pursuing the development of antibodies directed against human aspartyl (asparaginyl) beta-hydroxylase (HAAH) as novel agents for the treatment of cancer with liver cancer as its first intended indication. The Company is exploring both naked anti-HAAH antibodies as well as HAAH antibodies conjugated to chemotherapeutic agents. Panacea is also pursuing the development of diagnostic products based on HAAH gene expression and anti- HAAH antibodies. A test to determine responsiveness to a current therapy of choice in patients with chronic myelogenous leukemia utilizing HAAH gene expression is available through Panacea Laboratories. A proprietary blood- based assay has shown high sensitivity and specificity in the detection of a range of cancers, thus facilitating the diagnosis and therapeutic management of disease. Initial targets for the blood-based diagnostic products include prostate and liver cancers.

About Panacea Pharmaceuticals, Inc.

Panacea Pharmaceuticals, Inc. is a privately-held biopharmaceutical company focused on the development and commercialization of therapeutics and diagnostics for diseases with substantial, unmet clinical needs. The Company's product development strategy is based on novel therapeutic agents and approaches for cancer treatment, as well as acute and chronic neurodegenerative conditions, such as hypoxia-induced neurological insult, Parkinson's Disease, and Alzheimer's Disease. Panacea has an extensive patent portfolio covering its neurodegenerative and oncology technologies. Panacea Laboratories is a division of Panacea Pharmaceuticals, Inc.

More information about the Company is available at http://www.PanaceaPharma.com.

Except for historical information presented in this press release, matters discussed herein may constitute "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995. Forward- looking statements are based on the opinions and estimates of management only as of the date of this release and are subject to certain risks and uncertainties that could cause actual results to differ materially from any future results, performance, or achievements expressed or implied by such statements. Factors that might cause such a difference include, but are not limited to, uncertainties related to our access to capital, the progress, costs, and results of any clinical trials undertaken by us, progress of our research and development projects, and uncertainties related to whether our product candidates would ultimately achieve commercial success. We do not undertake any obligation to update publicly any forward-looking statement, whether as a result of new information, future events, or otherwise unless required by law.

Panacea Pharmaceuticals, Inc.
http://www.panaceapharma.com

Sunshine Pill For Prostate Cancer In 2009?

A tablet designed to emulate the healing power of the sun could be available for the treatment of advanced prostate cancer as early as 2009. But it remains to be seen whether the drug will be the revolution in prostate cancer care that its makers claim.

The drug, Asentar (DN-101), is based on vitamin D and is given to patients in the advanced stages of prostate cancer along with chemotherapy drugs. Drug makers came up with the idea because vitamin D from sunlight improves the prognosis of certain cancers. But taking natural levels of the vitamin has no effect. Novacea, the company that makes Asentar, produced a novel formulation that reproduces the healing effect without the dangerous side-effects of a vitamin D overdose. If the on-going phase III trial goes to plan, the new drug should be available in 2009, reports Chemistry & Industry, the magazine of the SCI.

'If the results of the phase III trial are as good as those of the phase II trial, that would be significant,' says Nick James, professor of oncology at the University of Birmingham. In the phase II trials, Asentar significantly improved survival rates, 9 months over patients taking chemotherapy drugs (taxotere) alone. 'On average, patients in the advanced stage of the disease survive about 18 months, so an extension of 9 months would be very significant in my view,' says James.

Asentar provides levels of vitamin D 50-100 times higher than normal. Patients would be expected to take one tablet once a week with their weekly regime of taxotere for three weeks out of every four.

Business analysts say Asentar is a potential blockbuster, because prostate cancer rates are expected to soar in the next few years. But James is not so sure. 'A confounding factor is that if you go looking for more cases of cancer, you will find them. But this does not give you an accurate estimate of how many people will go on to develop advanced disease. In fact death rates are going down, which means that the market for this drug is probably pretty static.'

James also points out that it is far from certain that the Phase III trials will repeat the success of early trials. 'The phase II trial used a less than optimal taxotere regime so the survival rate may have been artificially inflated,' he says. He points out, however, that it may be that the Asentar will eventually prove applicable in the earlier stages of the disease.

Prostate cancer is the second leading cause of cancer death in men. Prostate cancer kills one man every hour in the UK.

###

Chemistry & Industry

Please acknowledge Chemistry & Industry as the source of these items. If publishing online, please include a hyperlink to http://www.chemind.org/ Please note Chemistry & Industry uses '&' in its title, please do not correct to 'and'.

About Chemistry & Industry

Chemistry & Industry magazine from SCI delivers news and comment from the interface between science and business. As well as covering industry and science, it focuses on developments that will be of significant commercial interest in five- to ten-years time. Published twice-monthly and free to SCI Members, it also carries authoritative features and reviews. Opinion-formers worldwide respect Chemistry & Industry for its independent insight.

About SCI

SCI is a unique international forum where science meets business on independent, impartial ground. Anyone can join, and the Society offers a chance to share information between sectors as diverse as food and agriculture, pharmaceuticals, biotechnology, environmental science and safety. As well as publishing new research and running events, SCI has a growing database of member specialists who can give background information on a wide range of scientific issues. Originally established in 1881, SCI is a registered charity with members in over 70 countries.

Contact: SCI Press Office
Society of Chemical Industry

Adjuvant Radiotherapy For Pathologically Advanced Prostate Cancer: A Randomized Clinical Trial

UroToday.com- Extraprostatic prostate cancer (CaP) is detected in up to 50% of men at radical prostatectomy (RP). But as urologists, do we decide to initiate adjuvant radiotherapy (XRT) or wait for a biochemical recurrence and then start salvage XRT? Adjuvant therapy may improve outcomes by treating with a minimal residual disease burden, but some patients are potentially being treated without really having residual cancer and may do equally well with salvage therapy. This longstanding question was addressed in a prospective multi-institutional trial that began in 1988. The results appear in the November 15, 2006 issue of JAMA and are authored by Dr. Ian Thompson and colleagues.

Beginning in 1988, patients who had undergone RP and met 1 or more of 3 criteria for extraprostatic disease were eligible. The criteria were extracapsular tumor extension, positive surgical margins, or seminal vesicle invasion. A pelvic lymphadenectomy with no evidence of nodal metastases was required for inclusion.

Starting in 1995 patients who were at pre-defined low clinical risk for lymph node metastases did not require a lymphadenectomy. An undetectable PSA at enrollment was not required. Radiotherapy was delivered at a dose of 60-64 Gy. Follow-up included PSA and clinical scans. The primary study endpoint was metastasis-free survival. The assumption was that the primary endpoint, median metastasis-free survival would be 6 years and that adjuvant XRT would decrease this by one-third.

A total of 425 men were eligible for analysis and had been enrolled between 1988 and 1997 with follow-up through September 2005. Mean follow-up was 10.9 years. The actual median metastasis-free survival for the observation group in this study was 13.2 years, with 5- and 10-year metastasis-free survival of 84% and 63%, respectively. A total of 91 of the 211 patients (43%) in the observation group were diagnosed with metastatic disease or died (median metastasis-free estimate, 13.2 years) vs. 76 of 214 patients (35.5%) (median metastasis-free estimate, 14.7 years). The hazard ratio for metastasis-free survival with adjuvant XRT was 0.75 and not statistically significant. Among the 167 men total who were diagnosed with metastatic disease or who died, 115 (69%) died without documented metastatic disease. There were 35 cases of metastatic disease found in the observation group and 17 in the XRT group.

Regarding PSA relapse (defined as a PSA >0.4ng/ml), 112 of 175 (64%) in the observation group had PSA relapse compared with 60 of 172 (35%) in the adjuvant XRT group. Adjuvant XRT was associated with a significant reduction of PSA relapse (median PSA relapse-free survival 10.3 years for XRT vs. 3.1 years for observation). A total of 111 of 211 (53%) of patients in the observation group experienced a recurrence of disease of death, compared with 84 of 214 (39%) in the adjuvant XRT group. Adjuvant XRT was associated with a significant reduction in disease recurrence. A total of 83 of 211 (39%) of patients in the observation group died during follow-up (median survival 13.8 years) compared with 71 of 214 (33%) in the XRT group. The hazard ratio was 0.80, which was not statistically significant. Among patients in the observation group, 21% received hormonal therapy by 5 years, compared with 10% of the XRT patients.

Patients with disease beyond the prostate capsule or with positive margins had a 6.1 year median time to PSA relapse, compared with a 2.1 years median time to relapse in those with seminal vesicle invasion and 3.1 years for those with both pathologic findings. Complications in the XRT group were consistent with usual reports and higher than the observation group.

This study did not demonstrate its primary endpoint that adjuvant radiotherapy results in a significant reduction in metastatic disease. Despite prolonged follow-up, the rate of metastatic disease was significantly less than anticipated.

Ian M. Thompson Jr; Catherine M. Tangen; Jorge Paradelo; M. Scott Lucia; Gary Miller; Dean Troyer; Edward Messing; Jeffrey Forman; Joseph Chin; Gregory Swanson; Edith Canby-Hagino; E. David Crawford


JAMA. 2006;296:2329-2335.

Reviewed by UroToday.com Contributing Editor Christopher P. Evans, MD

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

To access the latest urology news releases from UroToday, go to:
www.urotoday.com

Copyright © 2006 - UroToday

PSA Screening Among Elderly Men With Limited Life Expectancies

UroToday.com - PSA screening is recommended in men starting at age 50 (45 for positive family history or African-American race) and stopping when the life expectancy decreases to below 10 years. A report in JAMA from Dr. Walter and colleagues determined the PSA screening rates among elderly veterans stratified into subgroups based upon age and a validated measure of health status that is strongly predictive of life expectancy.

A cohort study was performed using data from the VA Automation Center. In addition, claims linked to Medicare claims from the VA Information Resource Center were analyzed. The final analysis was based upon a final screen-eligible cohort of 597,642 men.

To validate that PSA tests in the cohort were primarily sent for screening purposes, an audit from a random sample of 100 medical charts of men at the San Francisco VA was performed with 87% agreement. Age was categorized into 4 groups; 70-74 years, 75-79 years, 80-84 years, and 85 years and older. The Charlson Comorbidity Index defined health status, which is a measure of 19 chronic diseases selected and weighted according to their associations with mortality.

Median age was 77 years and median Charlson score was 1.8. Thirty percent of men had a Charlson score of 0 (best health) and 15% had a score of 4 or more (worst health). To put this in perspective, 47% of men in worst health had been hospitalized during one year compared to 6% in best health. A total of 56% of elderly men (333,041 of 597,642) received a PSA test in 2003. 68% of these had their first PSA performed in the VA system whereas 32% were performed within Medicare. Age was the strongest predictor of PSA screening. PSA screening decreased with increasing age; 64% for men aged 70-74 and 36% for men aged 85 years or older. Rates of PSA screening in the cohort did not decrease as much as estimated 10-year survival decreases with advancing age.

Although the an increase in Charlson score from 0 to 4 is associated with more than a 4-fold increased risk of death, worsening health was associated with only a small decrease in PSA screening rates. Within each age group, worsening health had little influence on PSA screening rates. For example, among men aged 85 years and older, the PSA screening rate for those in best health was 34% vs. 36% for men in worst health. Non-clinical factors such as marital status and region of the country were more predictive of PSA screening than health in multivariate analyses.

Men with a low probability of living 10 years were still likely to undergo PSA screening. This is exemplified by 36% of men aged 85 years or older being screened while less than 10% of men in the age group are expected to survive 10 years.

Louise C. Walter; Daniel Bertenthal; Karla Lindquist; Badrinath R. Konety
JAMA. 2006; 296 :2336-2342.

Reviewed by UroToday.com Contributing Editor Christopher P. Evans, MD

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

To access the latest urology news releases from UroToday, go to:
www.urotoday.com

Copyright © 2006 - UroToday

Practice Patterns In Screening And Management Of Prostate Cancer In Elderly Men

UroToday.com - Prostate cancer (CaP) screening guidelines are clear about when to initiate screening but only state that it should be discontinued when a man's life expectancy decreases to less than 10 years. Using these criteria and the fact that a man in his mid-to upper 70s in the United States has a 10-year life expectancy, it is understandable that physicians might perform PSA screening in men older than 75 years. Dr. Konety and colleagues assessed the practice patterns of PSA screening by physicians in Iowa by individual physician survey. The authors note that Iowa has the fourth largest population older than 65 years in the US and the second greatest proportion of people older than 85 years.

A pilot tested survey instrument was sent to 3,105 licensed healthcare providers from internal medicine (n=702), family practice (n=1,740), urology (n=78), medical oncology (n=13), radiation oncology (n=20) and physician's assistants (n=555). Of the 3,105 individuals surveyed, 32% (997) responded; 792 on the first mailing and 205 on a second mailing. Most survey responders perform PSA screening in men 75 years and older and consent to screening at a patient's request.

The age to initiate screening varied by specialty with 45-50 years preferred by 43% of family practitioner, 36% of internists, 13% of oncologists and 47% of urologists. 54% of family practitioner, 62% of internists, 87% of oncologists and 51% of urologists preferred a screening initiation age of 51-60 years. A screening age of 61-70 years was preferred by 2% of family practitioner, 2% of internists and 2% of urologists. A preference to never stop screening was reported by 4% of family practitioner, 3% of internists, 3% of oncologists and 2% of urologists.

Provider age and specialty correlated with the decision to screen elderly men. Older providers (greater than 51 years) were significantly more likely to screen even in elderly men. Family practitioners were also more likely to screen elderly patient s compared to other types of providers.

The survey also asked about CaP treatment preferences in patients age 75 years or older. Watchful waiting was preferred by 45%, and of those who recommended active therapy, 14% suggested radiotherapy, 5% surgery and 27% hormonal therapy.

These data indicate that a majority of healthcare providers in the State of Iowa perform CaP screening in men older than 75 years. The authors suggest that this may represent a lack of awareness that benefits of screening decline with age.

KonetyВ BR, SharpВ VJ, VermaВ M, WilliamsВ RD, The Iowa Prostate Cancer Consensus PanelВ 
Urology 2006; 68(5):1051-56.

Reviewed by UroToday.com Contributing Editor Christopher P. Evans, MD

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Impact Of Androgen Deprivation Therapy On Physical And Cognitive Function, As Well As Quality Of Life Of Patients With Nonmetastatic Prostate Cancer

UroToday.com- Androgen deprivation therapy (ADT) is given for significantly longer periods of time, with patients being treated for biochemical failure in the absence of known skeletal metastasis. Dr. Joly and associates evaluated the physical and cognitive effects on patients receiving ADT and report their findings in the December 2006 issue of the Journal of Urology.

Between 2003 and 2004 57 eligible men treated with ADT for at least 3 months for localized CaP, as adjuvant therapy, or for biochemical failure after primary therapy were included in the study. Of these, 30 received ADT as adjuvant treatment following radical prostatectomy (n=7) or radiotherapy (n=23), and 27 for a rising PSA. An LHRH analogue was given alone in 48 men (84%) and 9 received maximal ADT. The median duration of ADT was 1.8 years. An age-matched control group of men without CaP was included in the study.

A physical test, the 6MWT was used to reflect the functional exercise level for daily physical activities. Quality of life questionnaires were used for fatigue and cognitive assessments. Neuropsychological tests also screened for cognitive impairment.

More controls were found to have social activities compared to patients (92% vs. 77%). No differences in previous medical or psychiatric history were found. Patients had lower median hemoglobin and serum testosterone levels. No difference in cognitive, physical and QoL measures was found between patient receiving ADT as adjuvant therapy and those receiving it for increasing PSA. Duration of ADT did not correlate between the different measures. Overall functioning was high in both controls and patients without statistically differences in any of the measures of physical function. Furthermore, there was no difference in the incidence or severity of cognitive dysfunction between patients and controls.

Fatigue was reported by 14% of patients compared to 4% of controls. Depression was also not noted with 89% of patients and 98% in the normal range. Loss of energy by one measure was reported by 36% of patients and 16% of controls, but was not associated with hemoglobin or testosterone levels. Over the relatively short treatment period reported, significant physical and cognitive affects of ADT were not noted.

JolyВ F, AlibhaiВ SMH, GalicaВ J, ParkВ A, YiВ QL, WagnerВ L, TannockВ IF
J Urol 2006; 176(6):2443-47.

Reviewed by UroToday.com Contributing Editor Christopher P. Evans, MD

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Spectrum Pharmaceuticals Initiates Phase 2b Trial For Ozarelix In Patients With Benign Prostate Hypertrophy

Spectrum Pharmaceuticals, Inc. (Nasdaq: SPPI) announced today that the first patient has been dosed in the company's Phase 2b study of ozarelix in the U.S. in patients with benign prostate hypertrophy (BPH). The trial will be conducted in accordance with the protocol recently accepted by the U.S. Food and Drug Administration (FDA).

The Phase 2b study is a randomized, double blind, placebo controlled trial of ozarelix enrolling approximately 100 men suffering from BPH. In this trial, patients will be dosed with 15 mg of ozarelix or placebo on day 1 and day 15 and will then be followed for six months. The study will evaluate safety and assess the efficacy of ozarelix as a treatment for BPH. The primary endpoint of the study is the improvement of BPH symptoms as measured by the International Prostate Symptom Score (IPSS), the standard method of assessing BPH symptoms. The study will also measure urine flow and quality of life. Data from the study will be used to support a New Drug Application (NDA) for ozarelix with the FDA for the treatment of BPH. Dr. Claus Roehrborn, Professor and Chairman at the UT Southwestern Medical Center at Dallas, Department of Urology, will be the lead investigator. Dr. Roehrborn is an internationally recognized leader in the diagnosis and treatment of BPH. "We are pleased to meet our objective of initiating the Phase 2b trial of ozarelix this month, and we are on track to initiate a Phase 3 trial in the second half of 2007 to evaluate long-term efficacy and safety of ozarelix courses given at six-month intervals," said Rajesh Shrotriya, M.D., Chairman, President and CEO of Spectrum Pharmaceuticals. "Based on results from our earlier Phase 2 trial in which clinical efficacy was maintained for 6 months following dosing, ozarelix may represent an important advance in the treatment of BPH for the more than 28 million American men who are currently suffering from this disease. Currently marketed therapies are limited by their relatively mild improvement in BPH symptoms, their bothersome sexual side effects and by the fact that compliance can be an issue because the treatments require daily dosing." In 2006, Spectrum reported results from a double-blinded, randomized, placebo-controlled, multi-center, dose ranging Phase 2 trial with ozarelix in patients suffering from BPH. While the primary efficacy endpoint was achieved at all dosage regimens in this trial and ozarelix was well tolerated, the best results were obtained with the 15 mg dose, in terms of improvement in the IPSS score. Importantly, with this dosage regimen, where the patient is dosed on day 1 and day 15, the clinical efficacy was maintained for 6 months. Using the 15 mg dose, the observed mean decrease in the IPSS score following placebo run-in at weeks 12, 20 and 28 was -8.6, -9.4 and -8.7, respectively (mean: 47% decrease from baseline). This improvement in the IPSS represented a highly statistically significant and clinically meaningful difference versus baseline (p<0.001) as well as versus placebo (p<0.0001) and was accompanied by significant improvement in urinary flow without any deterioration in sexual function.

About Ozarelix and Development Alliance with AEterna Zentaris

Ozarelix is a fourth generation Luteinizing Hormone Releasing Hormone (LHRH) antagonist administered as an intramuscular injection. In August 2004, Spectrum received an exclusive license from AEterna Zentaris to develop and market ozarelix for all potential indications in North America (including Canada and Mexico) and India.

In addition, Spectrum will receive 50 percent of any upfront and milestone payments, royalties and/or profits from sales of the product in Japan. Japanese rights for all potential oncology indications have recently been licensed to Nippon Kayaku, a key player in the Japanese oncology market.

Spectrum is developing ozarelix for benign prostatic hypertrophy (BPH), hormone-dependent prostate cancer and other indications.

About Benign Prostatic Hypertrophy

Benign prostatic hypertrophy is a non-cancerous enlargement of the prostate frequently occurring in men over the age of 50. According to the National Institutes of Health, BPH affects more than 50% of men over the age of 60 and as many as 90% of men over the age of 70 and it is estimated that there are currently more than 28 million men suffering from BPH in the United States.

The IPSS (also known as AUA symptom index) is a standardized scoring system which evaluates the seven principal symptoms of BPH. The enlargement can result in the gradual squeezing of the urethra, resulting in increased frequency or difficulty in urinating. Treatment options for BPH include surgery and medications to reduce the amount of tissue and increase the flow of urine. Current treatment options have limited efficacy, potentially leading to inadequate compliance. Medications currently available belong to two classes: alpha blockers (such as FLOMAX(R)[1], CARDURA(R)[2] and HYTRIN(R)[3]) which relax the muscles in the neck of the bladder and in the prostate, but have no direct effect on the prostate growth itself, and alpha reductase inhibitors (such as PROSCAR(R)[4] and AVODART(R)[5]), which can result in some reduction of the prostate size but have a very slow onset of action, and may be associated with impotence and decreased libido.

About Spectrum Pharmaceuticals

Spectrum Pharmaceuticals acquires, develops and commercializes a diversified portfolio of drug candidates that meet critical health challenges for which there are few other treatment options. Spectrum's expertise lies in identifying undervalued drugs with demonstrated safety and efficacy, and adding value through further clinical development and selection of the most viable and low-risk methods of commercialization. The company's pipeline includes promising early and late-stage drug candidates with unique formulations and mechanisms of action that address the needs of seriously ill patients, such as at-home chemotherapy and new treatment regimens for refractory disease. For more information, please visit http://www.spectrumpharm.com.

Forward-looking statement

This press release may contain forward-looking statements regarding future events and the future performance of Spectrum Pharmaceuticals that involve risks and uncertainties that could cause actual results to differ materially. These statements include but are not limited to statements that relate to our business and its future, Spectrum's ability to identify, acquire, develop and commercialize its portfolio of drug candidates, the Company's promising pipeline, that ozarelix may represent an important advance in the treatment of BPH, that we will initiate pivotal Phase 3 trials of ozarelix in BPH in the second half of 2007, the safety and efficacy of ozarelix and any statements that relate to the intent, belief, plans or expectations of Spectrum or its management, or that are not a statement of historical fact. Risks that could cause actual results to differ include the possibility that our existing and new drug candidates may not prove safe or effective, the possibility that our existing and new drug candidates may not receive approval from the FDA, and other regulatory agencies in a timely manner or at all, the possibility that our existing and new drug candidates, if approved, may not be more effective, safer or more cost efficient than competing drugs, the possibility that past results may not be indicative of future results, the possibility that price and other competitive pressures may make the marketing and sale of our generic drugs not commercially feasible, the possibility that our efforts to acquire or in-license and develop additional drug candidates may fail, our lack of significant revenues, our limited human and financial resources, our limited experience in establishing strategic alliances, our limited marketing experience, our limited experience with the generic drug industry, our dependence on third parties for clinical trials, manufacturing, distribution and quality control and other risks that are described in further detail in the Company's reports filed with the Securities and Exchange Commission. We do not plan to update any such forward-looking statements and expressly disclaim any duty to update the information contained in this press release except as required by law.

[1] FLOMAX is a registered trademark of Boehringer Ingelheim

[2] CARDURA is a registered trademark of Pfizer, Inc.

[3] HYTRIN is a registered trademark of Abbott Laboratories

[4] PROSCAR is a registered trademark of MERCK & CO., Inc.

[5] AVODART is a registered trademark of GlaxoSmithKline

Spectrum Pharmaceuticals, Inc.
http://www.spectrumpharm.com

Radical Prostatectomy For Octogenarians: How Old Is Too Old?

UroToday.com- There is no defined recommendation for when to stop prostate cancer (CaP) screening, except when the life expectancy decreases to less than 10 years. In the United States, it is relatively uncommon for a man to undergo radical prostatectomy (RP) as definitive therapy beyond the age of 75 years. Yet life expectancy for a man in his upper 70s is about 10 years. Some men older than age 80 are fit and demand definitive therapy in the form of RP. Dr. Thompson and colleagues at the Mayo Clinic, Rochester MN identified a group of 19 men over age 80 who underwent RP and report on their outcomes in the November issue of Urology.

From 1986 to 2003, 13,154 men were treated with RP at the Mayo Clinic. Of these, 19 (0.4%) were 80 years or older at surgery. Overall, their database revealed that 876 men were diagnosed with localized CaP during this time period. The clinical, pathological, oncologic and functional outcomes were retrospectively assessed.

Mean patient age was 81 years, median pre-operative PSA was 10.2ng/ml, all men had clinical T1-2 disease and no patient had known metastasis. The mean American Society of Anesthesiologists score was 2.4. Records indicated that 5 patients specifically demanded RP and were opposed to age discrimination and in addition, 5 patients were physicians. On pathology, 13 (68%) had organ-confined disease, 2 had pT3a, 4 had pT3b, and 3 had a positive surgical margin. Gleason score was 7 or greater in 11 men (58%) and all had a negative pelvic lymphadenectomy.

While no peri-operative complications occurred and 3 received a blood transfusion, but these men all had surgery prior to 1992. Median follow-up was 10.5 years and no patient died within the first year after RP. Three men died less than 10 years after RP and no patient died from CaP. Ten patients survived more than 10 years, with 7 alive at a mean follow-up of 12.8 years. No overall survival difference was found comparing the survival of these patients (79%) with patients 60-69 years old (84%) and 70-79 years olds (75%) from the Mayo database during the same time period. Four men experienced a biochemical recurrence of PSA level 0.4ng/ml or greater. One patient with a positive surgical margin received adjuvant radiotherapy.

Regarding functional outcomes, one year after RP, 14 patients (74%) were using less than 1 pad/day for incontinence, 2 used 1 pad/day, 2 needed 2 pads/day or more and 1 required an artificial urinary sphincter. Nerve sparing was not performed in these men.

To the authors' knowledge, this is the first report of RP in octogenarians. While their data supports that RP can be performed safely in these men with good outcomes, it does not answer the question whether it is necessary. Other non-definitive modalities such as active surveillance and delayed androgen deprivation might give comparable results but were not compared in this study.

ThompsonВ RH, SlezakВ JM, WebsterВ WS, LieberВ MM
Urology 2006; 685(5):1042-45

Reviewed by UroToday.com Contributing Editor Christopher P. Evans, MD

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

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Copyright © 2006 - UroToday

Management Of Severe Urethral Complications Of Prostate Cancer Therapy

UroToday.com- Urethral stenosis after prostate cancer therapy (PCT) occurs in 2% to 28% of patients and may manifest as anterior or posterior urethral stenosis. Post radical prostatectomy urethral stenosis occurs as bladder neck contractures but if the prostate is left in-situ, as in patients choosing radiation therapy, posterior urethral stenosis includes membranous urethral stricture, prostatic urethral stricture and bladder neck contracture. Rectourinary fistula is a rare complication occurring 1% to 1.8% after prostate cancer therapy.

A recent review by Elliot and McAninch from San Francisco examines the management of urethral stenosis and rectourinary fistula resulting from prostate cancer therapy. The review is published in the December 2006 issue of the Journal of Urology.

A total of 48 patients with urethral complications after treatment for prostate cancer comprised the study group. Sixteen of these patients had rectourinary fistulas and 32 had urethral stenosis. Mean time from first PCT was 5.3 years. During that time, patients underwent certain procedures including 1 urethrotomy in 20, multiple urethrotomies in 17, one dilation in 16, multiple dilations in 6, transurethral resection for stenosis on 9, urethral stent placement in 2, urethroplasty in 1, fistula repair in 4, and AUS placement in 4.

Of the 32 cases of stenosis, 5 occurred after brachytherapy (BT), 5 occurred after external beam radiotherapy (EBRT), 11 occurred after radical prostatectomy (RP), 4 occurred after BT plus EBRT and 7 occurred after RP plus EBRT. Of the 16 cases of fistula, 7 occurred after RP, 3 occurred after BT plus EBRT, 2 occurred after cryotherapy plus EBRT. Complications occurred more often in patients who had a form of radiation therapy.

Stenosis repair was successful in 23 of 32 cases (73%) utilizing an anastomotic urethroplasty in 19 cases, flap urethroplasty in 2, perineal urethrostomy in 2 and urethral stent in 9. Thirteen of the patients were incontinent after repair, mostly after bulbar urethra to bladder neck anastomosis.

Fistula repair was successful in 14 of 15 cases (93%) and this was established in a variety of ways. The authors subdivided the patients into 3 groups depending on fistula size and the presence or absence of urethral stenosis. The more severe the fistula, the less chance that a transanal approach was utilized and the higher chance that a pubectomy was required.

Urethral stenosis or rectourethral fistula following prostate cancer therapy can be managed by urethral reconstruction, such that normal voiding via the urethra is maintained, rather than abandoning the urethral outlet and performing heterotopic diversion. Utilizing principles outlined in this paper, repair can be accomplished with an acceptable rate of failure given the complexity of the cases.

ElliottВ SP, McAninchВ JW, ChiВ T, DoyleВ SM, MasterВ VA
J Urol. 2006 Dec; 176(6):2508-13

Reviewed by UroToday.com Contributing Editor Michael J. Metro, MD

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No Link Between Viral Findings In The Prostate And Subsequent Cancer Development

UroToday.com- Recently, mutations in genes associated with immune defense and a link to the development of prostate cancer (CaP) has been proposed by several scientific studies. In addition, epidemiologic reports suggest that men with prior history of sexually transmitted infections have an increased relative risk for development of CaP. Based upon these reports Dr. Bergh and associates from Umed University and Karolinska Institute, Sweden investigated whether the presence of genetic traces viral infections in the prostate correlated with histological inflammation and a subsequent diagnosis of CaP. They did not find an association and report this in the on-line version of the British Journal of Cancer.

The research was a case-control study of 402 patients with benign prostatic hyperplasia who underwent transurethral resection of the prostate. Median patient age was 64 years and specimens were paraffin-embedded. A total of 201 men developed CaP at least 6 months after the TURP. For each case, a control was randomly selected from a group of patients that did not develop CaP. The case-controls were matched for age, residence and year of surgery. TURP specimens were graded for degree of histological inflammation as mild or severe. DNA from prostate tissue was purified and checked for integrity. Tissue was examined for genetic traces of EBV, herpes simplex virus (HSV) 1 and 2, cytomegalovirus (CMV), adenovirus, HPV, polyoma viruses BKV and JCV and Candida albicans. Nested PCR assays were used for all except HPV and C. albicans. Positive PCR findings were verified by sequencing.

Of the 402 samples tested, 352 (87.6%) were positive for the human ОІ-globin gene. This suggested sufficient DNA quality. Of the 352 samples, 31 (8.8%) were positive for EBV and 10 (2.8%) for JCV. No other viral DNAs were detected. Of 240 samples that were available for C. albicans specific PCR, 2 (0.8%) were positive. The detection of EBV, JCV and C. albicans was then tested for correlation with subsequent CaP development. A total of 159 matched case-control pairs with complete information on EBV and JCV and 115 pairs with complete information for C. albicans were available. Of the 29 positive EBV samples, 15 (9.4%) were in the case group and progressed to CaP and 14 (8.8%) were in the control group. The two samples with C. albicans were found in the case group. There was no difference in the occurrence of severe inflammation in the EBV or JCV positive samples vs. virus-negative samples.

The outcomes of this study suggest that the examined viruses are unlikely to contribute to CaP development. However, the results are very methodology dependent and the incidence of samples with viral infection was less than 10% for every virus selected.

J Bergh, I Marklund, C Gustavsson, F Wiklund, H Grönberg, A Allard, O Alexeyev, F Elgh
British Journal of Cancer advance online publication 21 November 2006
doi:10.1038/sj.bjc.6603480

Reviewed by UroToday.com Contributing Editor Christopher P. Evans, MD

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Copyright © 2006 - UroToday