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


Contents
*Possible Causes and Prevention
*Delay In Surgery Of Three Months Decreases Survival For Bladder Cancer Patients
*Halozyme Therapeutics Completes Enrollment Of Chemophase Phase I Clinical Trial For Superficial Bladder Cancer
*Protein Patterns Can Be Used To Identify Bladder Cancer
*Clinical Benefits Of UroVysion(R) DNA Test Highlighted By Bladder Cancer Experts In Urology
*Cystectomy Vs. BCG For T1 High Grade Bladder Cancer - AUA 2006 - Society Of Urologic Oncology Meeting
*MDCT Shows Potential For Detecting Bladder Cancer Without Surgery Or Contrast
*Apoptosis Receptor Holds Potential As Urinary Marker For Bladder Cancer
*Matritech's NMP22(R) BladderChek(R) Test Can Save Lives And Reduce Expense Screening High Risk Populations For Bladder Cancer
*U.S. Genomics And Lahey Clinic Announce Collaboration To Study The Role Of MicroRNAs In The Prognosis Of Urologic Cancers
*Use Of Personal Permanent Hair Dye Is Not Linked To Bladder Cancer Risk
*Is There An Indication For Frozen Section Examination Of The Ureteral Margins During Cystectomy For Transitional Cell Carcinoma Of The Bladder?
*Reproductive Risk Factors for Incident Bladder Cancer: Iowa Women's Health Study
*Bladder Cancer Linked To Androgens And Androgen Receptor In Mice
*Clinical Utility Of Fluorescent In Situ Hybridization For The Surveillance Of Bladder Cancer Patients Treated With Bacillus Calmette-Gu?rin Therapy
*The Effect Of Ofloxacin On Bacillus Calmette-Guerin Induced Toxicity In Patients With Superficial Bladder Cancer: Results
*Compound Found In Cruciferous Vegetables Associated With A Decreased Risk Of Bladder Cancer
*Green Tea May Protect The Bladder From Becoming Inflamed
*Viventia Biotech Reports Final Vicinium(TM) Phase I/II Bladder Cancer Data At The American Urological Association Annual Meeting
*Transitional Cell Carcinoma - Optimizing Outcomes At Various Stages Of Bladder Cancer
*How Immunology Research Drives Treatment Of Bladder Cancer
*Ral GTPases And Friends: New Conspirators In Bladder Cancer Metastasis And Targets For Therapy
*Can Restaging Transurethral Resection Of T1 Bladder Cancer Select Patients For Immediate Cystectomy?
*Use Of Urinary Biomarkers For Bladder Cancer Surveillance: Patient Perspectives


 
Possible Causes and Prevention

Researchers at hospitals and medical centers all across the country are studying bladder cancer. They are trying to learn what causes the disease and how to prevent it.

At this time, the causes of bladder cancer are not fully understood. It is clear, however, that this disease is not contagious; no one can "catch" cancer from another person.

Some researchers study patterns of cancer in the population. They look for factors that are more common in people who get bladder cancer than in people who don't get this disease. Studying such patterns helps researchers identify risk factor for bladder cancer. However, most people with these risk factors do not get cancer, and many people who do get bladder cancer have none of the known risk factors.

Researchers have found that white people in the United States get bladder cancer twice as often as African-Americans, and men are affected about three times as often as women. People with family members who have bladder cancer may be more likely to get the disease as well. Most bladder cancers occur after the age of 55, but the disease can also develop in younger people.

Known and possible risk factors for bladder cancer include:
* Smoking.This is a major risk factor. Cigarette smokers develop bladder cancer two to three times more often than do nonsmokers. Quitting smoking reduces the risk of bladder cancer, lung cancer, and several other types of cancer, as well as a number of other diseases.
* Occupational risk. Workers in some occupations are at higher risk of getting bladder cancer because of exposure to carcinogen in the workplace. Increased risk is seen in people in the rubber, chemical, and leather industries, as well as in hairdressers, machinists, metal workers, printers, painters, textile workers, and truck drivers.

People who think they may be at risk for developing bladder cancer should discuss this concern with their doctor. The doctor may suggest ways to reduce the risk and can plan an appropriate schedule for checkups.
http://www.cancersociety.com/bladder_tp.cfm

Delay In Surgery Of Three Months Decreases Survival For Bladder Cancer Patients

29 Mar 2006

Bladder Cancer patients whose surgery was delayed for more than three months after their diagnosis were more likely to die from their disease than patients whose surgery was performed sooner, according to a study by researchers at the University of Michigan Comprehensive Cancer Center.

The study, published in the April Journal of Urology, looked at 214 patients diagnosed with muscle-invasive bladder cancer and treated with radical cystectomy, an operation in which the bladder is removed. The researchers found that patients whose surgery was delayed more than 93 days from the date of diagnosis had worse survival rates compared to patients whose surgery occurred in fewer than 93 days.

Thirty-nine percent of patients without a delay died, while 54 percent of patients with a delay died. The patients whose surgery was delayed lived on average only one year, and their three-year survival rate was 38 percent, compared to a three-year survival rate of 51 percent for patients whose surgery was not delayed.

The time from diagnosis to surgery ranged from four days to 175 days, with 26 patients having a delay of more than 93 days, roughly three months. The most common reason for delay was scheduling issues. Less frequent reasons were patients seeking multiple opinions, misdiagnosis or patients reluctant to be treated. Patient indecision was not a common cause of lengthy delays.

"Most of these causes for delaying surgery are potentially reversible, and physicians - despite busy schedules and the need for second opinions - need to be diligent about coordinating appointments and information in a timely way," says lead study author Cheryl Lee, M.D., director of the bladder cancer program at the U-M Comprehensive Cancer Center and assistant professor of urology at the U-M Medical School.

The researchers believe a delay in treatment could cause micrometastases, cancer cells that spread through the body but in small quantities that cannot be detected by standard imaging techniques. The short survival - less than a year - among patients whose surgery was delayed more than 93 days is similar to survival for bladder cancer patients in which it is known the cancer has spread.

Some causes of treatment delay were unavoidable and irreversible, such as the patient being too old for surgery or having other medical conditions that rule out surgery.

Cystectomy is standard treatment for bladder cancer that has invaded the nearby muscle. Typically, five-year survival rates after surgery are as high as 80 percent.

This year, an estimated 61,420 Americans will be diagnosed with bladder cancer and 13,000 will die from it, according to the American Cancer Society. The disease affects men three times more often than women.
http://www.medilexicon.com/medicalnews.php?newsid=40458

Halozyme Therapeutics Completes Enrollment Of Chemophase Phase I Clinical Trial For Superficial Bladder Cancer

07 Mar 2006

Halozyme Therapeutics, Inc. (Amex: HTI), a biopharmaceutical company developing and commercializing recombinant human enzymes, announced today it has completed patient enrollment for its Chemophase(TM) Phase I clinical trial. Chemophase is a novel investigational recombinant therapeutic being developed to enhance the delivery of chemotherapy.

The initial clinical protocol for Chemophase was designed to evaluate a single intravesical (into the bladder) administration of Chemophase along with the widely used anticancer drug mitomycin in patients with superficial bladder cancer. The Phase I study enrolled five patients with superficial bladder cancer. The objectives of the study were to determine the safety, tolerability and pharmacokinetics of Chemophase administered intravesically with mitomycin. The study was conducted at BCG Oncology in Phoenix, Arizona under the supervision of Donald L. Lamm, MD, the principal investigator.

According to data from the American Cancer Society, National Cancer Institute, American Urological Association, and Southwest Oncology Group Study, more than 100,000 patients have new or recurrent superficial bladder cancer in the U.S. every year. All of these patients may be potential candidates for Chemophase in the event it is approved as first-line treatment with mitomycin.
http://www.medilexicon.com/medicalnews.php?newsid=38959

Protein Patterns Can Be Used To Identify Bladder Cancer

01 Mar 2006

A pattern of 22 polypeptides (proteins) could help distinguish patients with Bladder Cancer from individuals with other malignant and non-malignant genitourinary diseases, according to researchers reporting in the March issue of The Lancet Oncology. "From signatures of polypeptide mass, we established a model for predicting the presence of cancer", says lead author Prof Dan Theodorescu (University of Virginia Health Sciences Center, Charlottesville, VA, USA).

Although cancer of the urinary bladder is a common disease with an estimated 63 210 new cases in the USA in 2005, the current diagnostic tests are not very specific or sensitive. Previous studies have identified biomarker (protein) patterns that would distinguish patients with urothelial carcinoma--the most common malignant disease of the urinary bladder--from healthy controls. However, Theodorescu and colleagues wanted to identify a specific protein pattern that would, in addition, distinguish patients with urothelial carcinoma from those with other urinary diseases that can present with similar clinical signs and symptoms as those associated with bladder cancer.

They used urine samples from 46 patients with urothelial carcinoma and 33 healthy volunteers to establish a protein model. This model was then refined further using 366 urine samples from individuals with malignant and non-malignant genitourinary diseases. Using one of these refined models, the researchers correctly identified between 86% and 100% of 31 patients with urothelial carcinoma, 138 people who had other genitourinary diseases, and 11 healthy individuals.

Prof Theodorescu states: "At present, we are applying these methods to the discovery of biomarkers that can predict tumour stage, recurrence, progression and treatment response in patients with bladder cancer".
http://www.medilexicon.com/medicalnews.php?newsid=38533

Clinical Benefits Of UroVysion(R) DNA Test Highlighted By Bladder Cancer Experts In Urology

18 May 2006

A review of multiple studies in the journal Urology indicates that UroVysion(R), a DNA-based urine test that detects key genetic changes in bladder cells, showed favorable clinical attributes not found in other available biomarkers in the detection of bladder cancer.

UroVysion, the first and only test approved by the U.S. Food and Drug Administration that uses DNA probes to identify chromosomal abnormalities associated with bladder cancer, is also known as "molecular cytology" because it assesses both morphologic cellular changes of conventional cytology and molecular DNA changes. The test is based on Abbott's proprietary fluorescence in situ hybridization (FISH) technology.

In the March 2006 supplement of Urology, one expert, J. Stephen Jones, M.D., of the Glickman Urological Institute, Cleveland Clinic Foundation, authored a review of nine published studies that compared UroVysion(R) to conventional cytology. In the reviewed studies, UroVysion outperformed conventional urine cytology -- a long-time standard test used in the examination of individual cells and small clusters of cells -- across all stages and grades of bladder cancer. He also noted that UroVysion detected recurrent cancer before the development of lesions visible by cystoscopy, the visual examination of the bladder with an endoscopic tool inserted through the urethra.

"Many urologists have historically overestimated the sensitivity of cystoscopy, which could explain the high rate of cancer recurrence after complete removal of visible tumors," Dr. Jones said. "We found that molecular cytology demonstrated an increased risk for tumor recurrence when it is positive and the cystoscopy is negative."

In other key findings, UroVysion:

Excelled when combined with cystoscopy. In one study, UroVysion, used in conjunction with cystoscopy, detected 97 percent of bladder tumorswhereas the traditional cytology in tandem with cystoscopy detected 88 percent of tumors;

-- Better detected high-grade urothelial carcinoma, such as carcinoma in situ (CIS), a high-grade tumor of flat appearance that is often difficult to detect via cystoscopy. High-grade tumors, like CIS, have the greatest chance of progression and death if undiagnosed and untreated. Across the reviewed studies, FISH detected 96 percent of these worrisome cases, whereas cytology detected 71 percent.

-- Is not affected by infection, hematuria (blood in urine), instrumentation (e.g., cystoscopy) or bacillus Calmette-Guerin (BCG) immunotherapy, the most commonly used agent for treatment of bladder cancer.

The March supplement to Urology is based on a meeting of medical experts, held on May 20, 2005, in San Antonio, Texas, to discuss the diagnosis and treatment of bladder cancer. The findings presented reflect the collective opinion of the panel. The meeting was jointly sponsored by the Postgraduate Institute for Medicine and Dane Garvin, Ltd. The meeting and publication of the proceedings were made possible, in part, by an unrestricted educational grant from Abbott.

Further data regarding the clinical benefits of UroVysion appeared in the December 2005 supplement to Urology. In that supplement, which featured prominent bladder cancer thought leaders from around the world, the International Consensus Panel on Cytology and Bladder Tumor Markers conducted extensive analyses of published studies of various marketed and in-development tumor markers. The summary findings of that independent consensus panel concluded that, of the marketed products, UroVysion:

-- Demonstrated high sensitivity to detect high-grade and high-stage tumors (83 percent to 97 percent), including carcinoma in situ (about 100 percent).

-- Showed overall sensitivity in the studies that varied between 69 percent and 87 percent, with a sensitivity to detect low-grade (36 percent to 57 percent) and low-stage (62 percent to 65 percent) tumors.

-- Exhibited high specificity across all grades and stages of tumors (>90 percent).

"The findings published in Urology confirm that UroVysion is a superior test as an aid in the detection of bladder cancer," said Timothy Stenzel, M.D., Ph.D., medical director, Abbott Molecular. "Because of its high sensitivity and its unique ability to detect chromosomal change, UroVysion provides physicians with deeper insight into detection of high-risk urothelial carcinoma and helps guide important treatment decisions."
http://www.medilexicon.com/medicalnews.php?newsid=43598

Cystectomy Vs. BCG For T1 High Grade Bladder Cancer - AUA 2006 - Society Of Urologic Oncology Meeting

24 May 2006

The annual meeting of the Society of Urologic Oncology took place on Saturday, May 20, 2006 during the annual American Urological Association Meeting in Atlanta, Georgia. In the afternoon session, Dr. Seth Lerner, Baylor College of Medicine moderated a session titled ?Cystectomy vs. BCG for T1 High Grade Bladder Cancer?. In his introduction, Dr. Lerner pointed out that the presence of CIS clearly worsens the prognosis of stage T1G3 TCC.

Dr. Mark S. Soloway, University of Miami School of Medicine presented the argument for management of stage T1 bladder cancer with intravesical BCG therapy. First, he argued to eliminate the term ?superficial? bladder cancer as it includes a heterogeneous group of tumors. However, many of these are not low risk and the term ?superficial? implies no invasion and low risk for progression. Dr. Soloway pointed out that cystectomy for stage T1 disease is over-treatment in 25-40% of patients. However, he showed data on 319 of his patients who had cystectomy. Of those, 30% were not organ confined. The 5-year estimated overall survival was 65% and the 69% for disease-specific survival. This serves as evidence, he said that we are currently waiting too long to treat many patients. Better patient selection through re-TUR will help to identify patients at risk for progression or understaging. Dr. Soloway also cited the excellent response rates to BCG in stage T1 tumors and that a significant percentage of these patients would never need to go on to cystectomy. Dr. Soloway referred to the data on BCG maintenance therapy and its role in decreasing tumor progression. Lower doses of BCG can minimize side effects without compromising the anti-tumor effects.

Dr. Eila Skinner, USC Norris Cancer Center presented the case for management of stage T1 bladder cancer with cystectomy. She discussed the risks of understaging T1 disease and the fact that metastatic bladder cancer is not curable. Between 37-39% of patients with T1G3 disease and CIS will be up-staged. Dr. Skinner was concerned that BCG may delay recurrence but may not impact long-term cancer specific survival. She pointed out that even with cystectomy, some patients went on to fail due to micro-metastatic disease. The USC series for patients who had cystectomy shows that the survival curves for T1 and T2 are extremely similar. As such, she felt that T1 and T2 were similar and should be treated the same. Dr. Skinner pointed out that cystectomy is an operation with low morbidity and mortality. The outcomes with orthotopic urinary diversion are excellent and in combination with extended pelvic lymphadenectomy give the best chances for cure.

By Christopher P. Evans, M.D.
http://www.medilexicon.com/medicalnews.php?newsid=43872

MDCT Shows Potential For Detecting Bladder Cancer Without Surgery Or Contrast

03 May 2006

MDCT urography is a promising technique for detecting bladder tumors both with and without contrast material, helping patients avoid an invasive test, according to a new study by researchers from the University of Michigan Health System in Ann Arbor, MI.

For the study, 92 patients with bladder cancers were evaluated with MDCT. The researchers were able to identify 87 of the 92 bladder tumors on MDCT, regardless of whether the portion of the bladder was opacified with contrast material or not. Usually, bladder cancer is detected by cystoscopy, an uncomfortable procedure in which an instrument is inserted into the urethra to sample or see inside the bladder. "Urologists often ask for MDCT to evaluate the ureters and kidneys for further disease. In doing so, we found that we saw most of the bladder cancers identified by cystoscopy on our MDCT, so we wondered if MDCT could be used to investigate the bladder on its own. Based on our study, it looks like this is a possibility," said Jonathan Willatt, MD, lead author of the study.

In addition, the researchers found that it didn't always matter whether contrast was used or not. "The problem with contrast material is that once it has passed from the ureters to the bladder it tends to opacify unevenly. When this happens, the doctors either roll the patient over repeatedly to mix the urine and contrast or administer a diuretic to get the patient to void and then allow the bladder to fill with contrast-enhanced urine. We found that we could see almost all of our tumors in the unopacified part," said Dr. Willatt. "With new CT technology we can scan so rapidly that if we time it right, and if we get the bladder full enough, we feel that there is scope for evaluating the bladder fully with CT which may obviate the need for the more invasive and less comfortable cystoscopy," he added.

The researchers also discovered that both CT and cystoscopy struggle with patients who have had previous bladder treatment such as surgery, radiotherapy or chemotherapy, so monitoring cancer recurrence is still a problem for both tests.

The full results of the study will be presented in May 2006 during the American Roentgen Ray Society Annual Meeting in Vancouver, BC.
http://www.medilexicon.com/medicalnews.php?newsid=42618

Apoptosis Receptor Holds Potential As Urinary Marker For Bladder Cancer

07 May 2006

UroToday.com - Cystoscopy remains the gold standard for detection of recurrent transitional cell carcinoma (TCC) of the bladder. Cytology and other markers are used to improve sensitivity and potentially decrease the frequency of cystoscopies.

A new marker, soluble Fas (sFas) holds promise as a new bladder marker according to a recent paper published in the April 15, 2006 issue of Cancer by Dr. Svatek and colleagues at the University of Texas, Southwestern Medical Center.

Programmed cell death, or apoptosis can be signaled through a variety of pathways. One pathway involves the transmembrane receptor Fas, which is activated by its ligand FasL to induce protease activation and degradation of chromosomal DNA. Dysregulation of Fas mediated cell death facilitates tumor development and progression. Soluble forms of Fas can result from alternative splicing and may protect tumor cells from host anti-tumor immunity. It is reported that blood and tissue levels of sFas are elevated in patients with TCC of the bladder.

The investigators found sFas elevated in the cell lysates and conditioned media from two aggressive TCC bladder cancer cell lines.

In patients, sFas was compared to cytology and NMP22 for the detection of recurrent TCC. The study cohort consisted of 188 patients with a history of TCC who presented for surveillance cystoscopy, 31 patients with other noncancerous urologic conditions and 10 healthy volunteers. Overall, 53% of patients had bladder tumors. Commercial assays were used to measure sFas and NMP22.

Levels of sFas were higher in patients with TCC as compared to controls and was associated with elevated NMP22 levels, positive cytology and advanced (>T1 tumor) stage. In the >75% sensitivity areas of the receiver operating characteristics curves, sFas was more specific than NMP22. However, while all three markers were associated with TCC in multivariate analysis, only cytology was associated with tumor stage >T1 in this analysis.

In this study, sFas independently predicted for TCC recurrence and outperformed NMP22, one of only two urine marker assays that are approved by the U.S. Food and Drug Administration.

By Christopher P. Evans, MD
http://www.medilexicon.com/medicalnews.php?newsid=42881

Matritech's NMP22(R) BladderChek(R) Test Can Save Lives And Reduce Expense Screening High Risk Populations For Bladder Cancer

02 Aug 2006

An article published in an early online view of the American Cancer Society's journal Cancer reports that screening for bladder cancer in high risk populations can save lives and reduce overall medical expenses. All other cancer screening programs save lives but increase expenses. Screening for bladder cancer with the NMP22(R) BladderChek(R) Test was less costly than not screening. The article will appear in the September 1 print issue of the journal.

Yair Lotan, M.D., Assistant Professor, Department of Urology, University of Texas Southwestern Medical Center, and his colleagues created a decision analysis model to assess cost-effectiveness and life years saved from screening versus not screening for bladder cancer in high risk populations. They found that the urine-based NMP22 BladderChek Test is cost effective for screening high risk populations based on its cost and accuracy in detecting bladder cancer.

"Cancer screening is generally considered a valuable tool for saving lives, but at this time it is limited to prostate, breast, colon, and cervical cancer. While the goal of cancer screening is to detect cancer early and save lives, it must be reasonably cost-effective if it is to be instituted widely," said Dr. Lotan.

High risk was defined as over 50 years of age with a smoking history and/or significant occupational exposure to toxins or dyes. The authors also took into consideration factors that limit the effectiveness of cancer screening, including survival benefit, disease prevalence, screening efficacy and cost.

The NMP22 BladderChek Test is a point-of-care assay administered in the doctor's office using four drops of urine with results available in 30 minutes. The test is marketed by Matritech (Amex: MZT), a leading developer and marketer of protein-based diagnostic products for the early detection of cancer.

Dr. Lotan suggests that bladder cancer is an ideal disease for screening a high risk population because the risk factors are well known. "The best possibility for reducing bladder cancer mortality is early detection," he emphasized. "The initial diagnosis of one out of four bladder malignancies currently occurs when the cancer is at an advanced stage. Bladder tumors detected early, when they are non-muscle invasive, are very treatable and the five-year survival rate is 95%. However, once the tumors become more advanced the survival rate drops steadily from 50% to 10%."

"This study goes beyond analyzing the cost per cancer detected. It is about the cost per life year saved and defines how effective a urine marker needs to be to perform as a screening tool. In the absence of screening, one in four bladder cancers is detected when it is already advanced, requiring expensive treatment and has reduced survival. Screening offers the potential for detecting cancers earlier, resulting in less extensive and less costly treatments, as well as improved survival," Dr. Lotan explained.

There will be more than 63,000 new cases of bladder cancer in the U.S. this year and it is the 5th most common cancer among men and women. It is significantly more common and has a higher mortality than cervical cancer. It is almost as common in men as colon cancer. The prevalence of bladder cancer in the U.S. is higher than lung cancer and its prevalence in women is similar to ovarian cancer. Currently there are more than 500,000 Americans with a history of bladder cancer.

The Lotan analysis indicated urine-based bladder cancer markers could reduce mortality and save costs in a high-risk population, if the cost of the urine test is less than $126. Overall the Lotan model projected a gain of three life years and $101,000 saved from reduced treatment costs per 1,000 people screened based on a population with 4% incidence of bladder cancer. He noted that adjusting for other causes of mortality did not vary the results significantly, and screening versus not screening is more cost-effective as long as the cancer incidence is greater than 1.6%.

Nationally, bladder cancer has the highest cost per patient of the major cancers from diagnosis to death. This year alone in the U.S. it's estimated that bladder cancer will cost $4 billion in direct costs.

"With the FDA approval of the NMP22 Test for detecting cancer in high risk patients, the healthcare community has a test that could be employed in screening," commented Dr. Lotan.

In the article, the authors pointed out that another advantage for bladder cancer screening is the low cost of the NMP22 BladderChek test, so those patients without cancer do not have a high cost burden compared to cancer screening using colonoscopy or mammography.

Another recent study has proven that screening reduced bladder cancer mortality. Results of the long-term study were reported at the 2006 annual meeting of the American Urological Society (AUA) meeting by Edward Messing, M. D., Chairman of the Urology Department, University of Rochester Medical Center. His 14-year follow up of patients screened for bladder cancer showed that no patients who underwent screening died from bladder tumors, whereas 20% of unscreened patients did die from bladder cancer. The tumors found by screening were diagnosed at earlier stages, thereby improving outcomes. Overall mortality was significantly lower in screened patients (43%) compared to those whose were not screened (74 %). Dr. Messing is also a co-author of the two studies on the NMP22 BladderChek Test published in JAMA.

Implementation of a screening strategy requires a prospective, randomized trial to assess both the detection accuracy in asymptomatic individuals and the impact of screening on cancer-specific mortality. Dr. Lotan has initiated such a screening clinical trial, and he believes that in the meantime, this model will help healthcare professionals identify at risk populations that would benefit from bladder cancer screening.

About the NMP22(R) BladderChek(R) Test

The NMP22(R) BladderChek(R) Test was developed and commercialized by Matritech, a leading developer and marketer of protein-based diagnostic products for the early detection of cancer. The NMP22 BladderChek Test detects elevated levels of the NMP22 protein marker in a single urine sample. Most healthy individuals have very small amounts of the NMP22 protein marker in their urine, but bladder cancer patients commonly have elevated NMP22 levels, even at early stages of the disease.

The NMP22(R) BladderChek(R) Test, a painless and noninvasive assay, is the only in-office test approved by the FDA for both the diagnosis and monitoring of bladder cancer. It is used in a physician's office, requires only four drops of urine and results are available in 30 minutes - during the patient visit, allowing a rapid and accurate way to aid in the detection of bladder cancer. The NMP22 BladderChek Test is reimbursed by Medicare and many medical insurers and has an average cost of less than $30. It also has been shown to detect over three times as many cancers as the commonly used laboratory based urine cytology test.

Two studies published in the Journal of the American Medical Association (JAMA) in February 2005 and January 2006 reported on clinical data showing the NMP22 BladderChek Test, used in combination with cystoscopy (a visual examination of the interior of the bladder using a scope inserted through the urethra), for the diagnosis and monitoring of bladder cancer detected up to 99% of bladder malignancies. The NMP22 BladderChek Test also detected cancers that were missed during an initial cystoscopic examination, most of which were high grade. In other clinical study analyses it was shown to detect 100% of the aggressive tumors, one of which was muscle invasive, in women with symptoms or risk factors for bladder cancer. It was also reported to detect all of the cancers that occurred in the upper urinary tract of patients with risk factors or symptoms of bladder cancer. Cystoscopy did not identify these tumors because they were outside the viewing area of the instrument.
http://www.medilexicon.com/medicalnews.php?newsid=48528

U.S. Genomics And Lahey Clinic Announce Collaboration To Study The Role Of MicroRNAs In The Prognosis Of Urologic Cancers

20 Oct 2006

U.S. Genomics Inc. and Lahey Clinic announce the signing of a discovery agreement to study the role microRNAs play in the development of urologic cancers. The objective of the collaboration is to develop more accurate prognoses for bladder and prostate cancer patients. The collaboration combines U.S. Genomics' patented Trilogy(R) 2020 platform and Direct(TM) miRNA assay with Lahey Clinic's expertise in the analysis of tumor progression and experience in disease management.

"This collaboration is intended to expedite the development of next-generation molecular diagnostic tests to determine the prognosis of several major urologic cancers," said John Libertino M.D., Chairman of the Department of Urology, Lahey Clinic.

"MicroRNAs hold great promise as biomarkers for several disease states, and we are very pleased to be working with U.S. Genomics to explore these new diagnostic markers for urologic oncology patients," said Ian Summerhayes, Ph.D., Executive Director of Research, Lahey Clinic Medical Center.

"U.S. Genomics is excited about working with Lahey Clinic to study the potential for microRNA-based tests for the prognosis of bladder and prostate cancer," said John Canepa, CEO and President of U.S. Genomics. "Use of our Trilogy(R) 2020 single molecule detection platform and assays partnered with Lahey Clinic's unique expertise and the guidance of Drs. Libertino and Summerhayes has the potential to result in significantly more accurate prognostic tests for these diseases," added Duncan Whitney, VP, Research & Development (U.S. Genomics).
http://www.medilexicon.com/medicalnews.php?newsid=54637

Use Of Personal Permanent Hair Dye Is Not Linked To Bladder Cancer Risk

21 Nov 2006

UroToday.com - An occupational exposure to hair dyes by hairdressers and barbers is shown to increase their bladder cancer risk. Hair dyes contain small amounts of aromatic amines, which are shown to be carcinogenic in animals. Prior to 1980, the formulations contained much higher contents of carcinogens. In the September 2006 issue of Cancer Epidemiology Biomarkers and Prevention, researchers from M.D. Anderson Cancer Center report that personal use of hair dyes does not increase the risk of bladder cancer.

The study included 712 bladder cancer cases and 712 healthy controls from M.D. Anderson Cancer Center and Baylor College of Medicine. All cases were newly diagnosed and had not received chemotherapy or radiotherapy. Demographic data was collected to include tobacco use, work history and personal hair dye use.

The bladder cancer cohort had a higher percentage of current (27%) and ever smokers (73%) compared to controls (9% and 52%). The percentage of cases reporting ever use of hair dye was similar to that of the controls. The odds ratio for any use of hair dye products did not demonstrate a difference. The association between duration of use, frequency of use, lifetime use, age at first use and bladder cancer risk showed no associations. Even patients using the more carcinogenic versions of hair dyes prior to 1980 were not found to be at increased risk.

These data suggest that permanent hair dye usage does not contribute to the development of bladder cancer.
http://www.medilexicon.com/medicalnews.php?newsid=57129

Is There An Indication For Frozen Section Examination Of The Ureteral Margins During Cystectomy For Transitional Cell Carcinoma Of The Bladder?

11 Jan 2007

UroToday.com- While ureteral frozen sections are routinely performed at the time of radical cystectomy, data from Memorial Sloan-Kettering, Johns Hopkins, and Penn have previously suggested that they may not be necessary in all patients. Perhaps most physicians continue to perform them because guidelines for patient selection have not been established.

In the December issue of the Journal of Urology, Schumacher, Studer, and colleagues report their experience with this very issue after reviewing their extensive database of 805 cystectomy procedures performed over a 20-year period.

Of 805 cystectomies performed, 4.8% of patients showed a positive ureteral frozen section and 3.6% exhibited a positive margin on the ureteral permanent section. Eighty percent of patients with positive frozen sections had a history of bladder carcinoma in situ.

If the ureters were divided proximal to the common iliac vessels, the risk of transitional cell carcinoma or CIS in the most proximally resected segment was 1.2%, regardless of the frozen section. This was the most important finding of the study. Of the entire cohort, only 0.3% (2/805) developed recurrence at the ureteroileal anastomosis.

In conclusion, the authors recommend that ureteral frozen sections be performed at the time of cystectomy only if the patient has a history of bladder CIS. Routine frozen sections are not recommended as long as the ureters are divided proximal to the iliac vessels.
http://www.medilexicon.com/medicalnews.php?newsid=60539

"Reproductive Risk Factors for Incident Bladder Cancer: Iowa Women's Health Study,"

03 Apr 2007

International Journal of Cancer: Anna Prizment of the University of Minnesota School of Public Health and colleagues followed 37,459 women ages 55 to 69 living in Iowa from 1986 to 2003 and examined factors associated with bladder cancer, Reuters Health reports. None of the women had cancer when the study began. During the study period, 192 women, or 0.5%, were diagnosed with bladder cancer at an average age of 73. The study found that after adjusting for age and smoking habits, a woman's likelihood of developing bladder cancer increased as the age at which she started menopause decreased. According to the study, women who reached menopause between ages 43 and 47 had a 32% higher risk of developing bladder cancer than women who reached menopause at age 48 or older. The risk increased to 60% for women who reached menopause at age 42 or younger, the study found. The risk factors were the same whether menopause was natural or the result of surgery. In addition, the study found that other reproductive factors -- such as age when menstruation began, age at first birth, number of births, use of hormone replacement therapy, infertility, fibroids, ovarian cysts or endometriosis -- were not linked to bladder cancer risk. Prizment said that the decrease in estrogen after menopause "could lead to an increased number of urinary tract infections associated with bladder cancer." She added that it is "too early to make any definite conclusions" because the biological cause for the association is "unclear" (Reuters Health, 3/28).
http://www.medilexicon.com/medicalnews.php?newsid=66790

Bladder Cancer Linked To Androgens And Androgen Receptor In Mice

08 Apr 2007

Male sex hormones and their receptors may be involved in the development and progression of bladder cancer, according to a study in mice.

Men have a considerably higher incidence of bladder cancer than women, though the reasons remain a mystery. Bladder cancer has been linked to exposure to cigarette smoke and industrial chemicals, but it was not previously considered to be influenced by male sex hormones, called androgens.

Chawnshang Chang, Ph.D., of the University of Rochester Medical Center in Rochester, N.Y., used a chemical carcinogen to induce bladder cancer in normal male and female mice and in mice lacking functional androgen receptors. They also treated human bladder cancer cell lines to reduce androgen levels or androgen receptor activity. Some of these cell lines were injected into mice.

None of the androgen receptor-free mice developed bladder cancer when treated with the carcinogen, whereas more than 92 percent of the normal male mice and 42 percent of the normal female mice did. Human bladder cancer cells with reduced androgen levels or androgen receptor activity grew more slowly in culture and in mice then cells with normal androgen and androgen receptor levels.

"The results presented here have the potential to provide the basis for the development of new preventive or therapeutic approaches for bladder cancer, via targeting androgens and the [androgen receptor]," the authors write.
http://www.medilexicon.com/medicalnews.php?newsid=67079

Clinical Utility Of Fluorescent In Situ Hybridization For The Surveillance Of Bladder Cancer Patients Treated With Bacillus Calmette-Gu?rin Therapy

21 May 2007

UroToday.com- Adjuvant intravesical therapy with BCG is commonly used to decrease the probability of recurrence and progression in patients with bladder tumors. While this therapy works in a fair proportion of patients, there are those who recur and even progress onto muscle-invasive stages. It is crucial that we identify means of differentiating potential 'responders' from 'non-responders' so that we might offer them alternative therapy (including cystectomy) prior to disease progression.

In the March issue of European Urology, Mengual and colleagues suggest that the multiprobe fluorescent in situ hybridization (FISH) assay (known as Urovysion? in the US) might be useful for determining the response of patients to BCG. Of 65 patients enrolled in the study, 85% demonstrated a positive FISH pre-BCG (i.e. after resection). When FISH was performed on bladder washing after the last of 6 weeks of BCG instillation (at an average of 2.9 mos, range 2 to 6 months after BCG), 45% had a positive post-BCG FISH result. If a patient with a positive pre-BCG FISH remained positive post-BCG, his or her likelihood of developing a recurrence was 2.96 times that of someone who converted to a negative post-BCG FISH (48% versus 23%, p = 0.02).

The results presented in this study support the use of FISH as a surveillance modality but the authors claim that it is useful in risk-stratification of patients treated with BCG. It is not surprising that patients with persistent disease (positive pre and post BCG FISH) should be at higher risk of recurrence, as was demonstrated by Kipp et al (Journal of Urology, 2005). What is surprising, however, is that if a patient converted from a negative pre-BCG FISH to a positive post-BCG FISH, this did not significantly alter the risk of recurrence (p=0.61). Furthermore, the pre-BCG FISH status was not a predictor of either disease recurrence or progression, which contrasts with prior reports. Notably too, there were nine false negative post-BCG FISH results and fourteen false positive post-BCG results (which might be an artifact of the short duration of follow-up of patients with a mean of 15.9 months (median not reported).

Thus, until more conclusive data (with longer follow-up) are available, the use of FISH after BCG therapy can be supported as a surveillance modality, but treatment decisions should not be based on findings from this one test alone.
http://www.medilexicon.com/medicalnews.php?newsid=71564

The Effect Of Ofloxacin On Bacillus Calmette-Guerin Induced Toxicity In Patients With Superficial Bladder Cancer: Results

20 May 2007

UroToday.com- BCG immunotherapy is the current 'gold standard' for treatment of non-muscle invasive bladder cancer. It is the only therapy which has been shown to decrease both recurrence as well as progression however, for maximal benefit it is important that patients receive 'maintenance' therapy up to 3 years. Nonetheless, practitioners often find that patients are unable to tolerate such therapy due to significant side effects thus limiting the number of doses each patient receives.

There are numerous proposed methods in which the side effect profile of BCG instillation can be reduced including, careful attention to instillation technique and reduction in dose after sensitization of patients. In an interesting and promising study, Colombel and colleagues studied the effect of quinolone antibiotic administration on improving the tolerance of intravesical BCG instillations following prophylactic ingestion of ofloxacin. This is a secondary objective of evaluating the effect on therapeutic efficacy of BCG instillations, since prior reports have suggested in vitro efficacy of such antibiotics against bladder cancer cells. The study randomized patients into 2 groups, one group (n= 57) received ofloxacin 6 h after 1st micturition and 10-12 h after 1st ingestion after each BCG (6+3) instillation and was compared to group two a placebo group (n=58).

The authors found that ofloxacin significantly decreased the incidence of class II or higher moderate and severe adverse events by 18.5%, as well as class III events by 21.5% (p=0.019). Compliance with BCG treatment was also improve with 80.7% of patients in the ofloxacin group who were able to receive all 9 instillations compared with 65.5% in placebo group (p = 0.092). At 12 months recurrence and progression rates both groups were similar at 12.7% and 17.2%, and 5.5% and 1.7%, respectively. It should be noted however, that that study was not powered to demonstrate equivalence of efficacy.

This is the first study to show that adjuvant antibiotic prophylaxis is a valid strategy to prevent BCG-related side effects and improve patient compliance with no evident loss of efficacy. This strategy, combined with dose reduction of BCG should allow most patients to receive the 'full prescribed course' of BCG thus improving their odds of response to therapy.
http://www.medilexicon.com/medicalnews.php?newsid=71535

Compound Found In Cruciferous Vegetables Associated With A Decreased Risk Of Bladder Cancer

20 May 2007

Isothiocyanates (ITC) are compounds found in cruciferous vegetables such as broccoli, cauliflower, kale, turnips, collards, Brussels sprouts, cabbage, radish, turnip and watercress.

They exert their anti-oxidant effect via down regulation of cytochrome p450 enzyme levels and induce apoptosis by activating Phase II detoxifying enzymes. Experimental data has suggested that these compounds may protect against the genesis of bladder cancer.

In the May 15th issue of the International Journal of Cancer, Zhao and colleagues from the Departments of Epidemiology and Urology at the M.D. Anderson Cancer Center report on an epidemiological study evaluating the relationship between ITC intake and bladder cancer risk.

The cohort consisted of 697 patients with newly diagnosed bladder cancer and 708 healthy controls matched by age, sex, and race. Dietary questionnaires were available for all patients. The dietary intake of ITCs was compared with bladder cancer risk and with the expression of genetic polymorphisms for the arylamine N-acetyltransferases 2 (NAT) and glutathione S-transferase genes.

Median ITC intake per day was significantly lower in bladder cancer patients than in controls (0.23 vs. 0.33, p < 0.001). High ITC intake was associated with 29% lower risk of bladder cancer (odds ratio = 0.71, 95% CI 0.57 to 0.89). This anti-cancer effect was seen more commonly in men, in patients age 64 or older, and in smokers. NAT2 slow acetylators exhibited an increased risk of bladder cancer in Caucasians compared with rapid acetylators (OR = 1.31, 95% CI 1.02 to 1.69). The decrease in bladder cancer risk associated with ITC intake was not associated to NAT2, GSTM1, or GSTT1 genotype expression.

This well-conducted study for the first time demonstrates that consumption of cruciferous vegetables with a high content of isothiocyanates such as broccoli, cauliflower, kale, turnips, collards, Brussels sprouts, cabbage, radish, turnip and watercress may offer a protective advantage against bladder cancer. Whether increasing ITC intake in bladder cancer patients improves treatment response and prevents recurrence remains to be studied.
http://www.medilexicon.com/medicalnews.php?newsid=71521

Green Tea May Protect The Bladder From Becoming Inflamed

22 May 2007

Herbal agents could be used to treat inflammatory bladder diseases, according to a preliminary study that looked at the ability of green tea to protect bladder cells from inflammation. The University of Pittsburgh School of Medicine study, presented at the annual meeting of the American Urological Association (AUA) in Anaheim, Calif., found that components of green tea protected bladder cells from damage in culture. The study is Abstract 299 in the AUA proceedings.

Green tea, reported to have many health benefits, is rich in powerful antioxidants that make it a possible remedy for many medical conditions. It is comprised of catechins - plant metabolites that provide it with many anti-oxidative properties.

"We discovered that catechins found in green tea protected both normal and cancerous bladder cells from inflammation when we exposed the cells to hydrogen peroxide," said Michael B. Chancellor, M.D., professor of urology and gynecology at the University of Pittsburgh School of Medicine. "Although further studies are needed, these results indicate herbal supplements from green tea could be a treatment option for various bladder conditions that are caused by injury or inflammation."

In the study, normal and cancerous bladder cells were exposed to two major catechin components of green tea, epigallocatechin gallate (EGCG) and epicatechin gallate (ECG), for 23 hours. Both significantly protected cell lines from exposure to hydrogen peroxide, which damages or kills cells. The concentrations of EGCG and ECG used in the study were at levels that may be achieved through dietary intake.
http://www.medilexicon.com/medicalnews.php?newsid=71579

Viventia Biotech Reports Final Vicinium(TM) Phase I/II Bladder Cancer Data At The American Urological Association Annual Meeting

25 May 2007

Viventia Biotech Inc., a privately held biopharmaceutical company advancing a portfolio of novel antibody products focused on cancer, today reported final data from its recently completed dose escalation Phase I/II clinical trial of Vicinium(TM) in patients with high risk, non-invasive bladder cancer. The results were presented at the 102nd Annual Meeting of the American Urological Association, which runs from May 19-24, 2007 in Anaheim, California. Vicinium(TM) is a fusion protein comprised of a humanized antibody fragment specific for the antigen EpCAM, conjugated to a cytotoxic protein, Pseudomonas exotoxin A.

The trial enrolled 64 patients who were refractory or intolerant to standard treatment (BCG therapy). Patients were dosed on a weekly basis for 6 weeks at escalating dose levels using intravesical instillation. Although designed as a phase I study, an efficacy analysis demonstrated that only 7% of these high risk patients progressed during the study period. Vicinium(TM) was very well tolerated at all dose levels with no maximum tolerated dose reached and no patient had a dose reduction or withdrawal due to toxicity.

"Patients with non-invasive bladder cancer, which comprise the majority of bladder cancers, that progress after failing conventional treatments usually require complete removal of the bladder to prevent further disease progression and avoid metastasis to other organs. Vicinium(TM), which was well-tolerated and provided an overall 93% disease control rate in a very high risk population, has the potential to someday substantially delay or eliminate the need for these more drastic options," said Dr. Nick Glover, President and CEO of Viventia Biotech. "Moreover, Vicinium(TM) has demonstrated an early safety profile far more favorable than the established therapies."

Patients were also monitored for duration of response following the completion of the protocol. Ongoing post hoc analyses demonstrated a sustainable response lasting more than 6 months in most of these patients, with many patients still disease free out to 12 months. Sustainability of response is being specifically assessed in an ongoing open-label Phase II trial of Vicinium(TM), which is currently enrolling patients with locally persistent non-invasive Cis bladder cancer in Canada and the U.S. Further details on Vicinium(TM) and this clinical trial are available at http://www.vicinium.com.

These data were presented by Dr. Michael Jewett, the principal investigator on the trial. Dr. Jewett is a Professor of Surgery (Urology) at the University of Toronto, a member of the Department of Surgical Oncology of Princess Margaret Hospital and a clinician investigator at the University Health Network. From 1991 to 2002, Dr. Jewett was the Chairman of the Division of Urology at the University of Toronto and Head of Urology at the University Health Network, which incorporates Princess Margaret Hospital. Preliminary results from this trial were presented at the 2006 ASCO meeting.

Viventia's lead product, Proxinium(TM), is being developed to treat late stage, locally advanced head and neck cancer and is currently enrolling patients in its TARGET trial, a pivotal Phase III global clinical trial that is also expected to complete accrual by the end of 2007. Vicinium(TM) and Proxinium(TM) are Armed Antibodies(TM) that target the cancer antigen EpCAM.

Viventia Biotech retains full global product rights to Proxinium(TM) and Vicinium(TM). The Company is seeking partners for Proxinium(TM) and Vicinium(TM) capable of complementing Viventia's development expertise with their global sales, marketing and commercial capabilities.
http://www.medilexicon.com/medicalnews.php?newsid=72086

Transitional Cell Carcinoma - Optimizing Outcomes At Various Stages Of Bladder Cancer

26 May 2007

UroToday.com - In a session moderated by Dr David Wood at the SUO meeting held during the 2007 AUA meeting in Anaheim, a panel of experts explored various issues pertaining to new standards of care with respect to management of bladder cancer. The panel consisted of Drs Harry Herr, Badrinath Konety, John Stein and Cora Sternberg.

The first question posed was whether patients who present with a new diagnosis of bladder tumor should receive intravesical mitomycin as is recommended by various panel guidelines. Surprisingly, the panel was divided with regards to their recommendations. Dr Konety presented data from SEER analysis which suggested less than 1% of patients actually receive intravesical peri-operative therapy, despite clear evidence that it is beneficial. Panel members discussed reasons for this, including risk of absorption with aggressive TUR and variations in risk assessment. A survey of the audience suggested that European Urologists are more likely to use peri-operative intravesical chemotherapy than North American Urologists.

The second issue was that of re-resection after initial TUR. The panel members agreed that a patient with high grade T1 tumor should undergo re-resection 3-4 weeks after initial resection, regardless of who performed the initial resection. Dr Herr presented his data which demonstrates that patients with persistent or recurrent T1 disease on re-TUR have a poor prognosis and might be better served with initial cystectomy. However, most panel members would still attempt a trial of intravesical therapy.

The next discussion point surrounded that of neoadjuvant chemotherapy for patients undergoing radical cystectomy for muscle invasive tumors. Dr Cora Sternberg discussed the meta-analysis which suggests a 5% increase in survival with cisplatinum based neoadjuvant chemotherapy as well as the 9% increase survival with adjuvant chemotherapy, while cautioning that the adjuvant chemotherapy data must be viewed with the knowledge that the confidence intervals were wide. Most panel members agreed that neoadjuvant chemotherapy should be considered for patients at high risk, but were divided as to whether they would recommend to same for all muscle-invasive cancers. The MD Anderson Cancer Center study which suggested equivalent tolerance of pre and post-operative chemotherapy was discussed and the panel agreed that further risk stratification is needed.

A final point of discussion was the extent of node dissection during radical cystectomy. Dr Stein presented data which suggested that removing more nodes improved survival. The panel agreed that while there is no consensus, less than 10 nodes is probably insufficient in most patients. The panel also discussed the possibility of using number of nodes removed as a surrogate for quality of surgical therapy.

In closing, Dr Wood stated that urologists in the country treating bladder cancer patients need to be more aware of the current state of the art therapies so that we as a community might be able to optimize outcomes at every stage of bladder cancer.
http://www.medilexicon.com/medicalnews.php?newsid=72241

How Immunology Research Drives Treatment Of Bladder Cancer

26 May 2007

UroToday.com - Dr. Michael O'Donnell, University of Iowa presented "How Immunology Research Drives Treatment of Bladder Cancer" in the session "Target Selection in Renal Cell Carcinoma and Bladder Cancer".

Dr. O'Donnell started by citing the some history relating to immunotherapy and cancer. He stated that in 1891 Coley fist injected cancers with bacterial toxins and saw tumor shrinkage. In 1929 Pearl noted that lower cancer rates in tuberculosis patients by autopsy series. In 1976 Morales used intravesical BCG in bladder cancer patients. Use of BGC resulted in decreased tumor cells in cytology specimens, but more neutrophils, suggesting an immune response.

Cytokine production of interleukins is central to the immune response. T cells are stimulated to the bladder after BCG therapy and are present for months thereafter. Interferon-gamma (IFN-gamma) is upregulated and participates in cellular immunity. IFN-gamma is always the last cytokine to come up and may be influenced by more proximal cytokines in the pathway. IL-10 knockout experiments showed that IFN-gamma is critical to the response.

IFN-gamma production is from BCG-stimulated human peripheral blood mononuclearcytes. Cox-2 inhibitors or indocin also inhibit IFN-gamma expression. BCG + IFN-gamma accentuates a type I cytokine response, suggesting that IFN-gamma may suppress IL-10. Response to BCG was increased if IFN-gamma was added. In fact, adding IFN-gamma and decreasing BCG maintains effectiveness.

TRAIL, an apoptosis inducing ligand was found to have higher urine levels in BCG responders vs. non-responders. TRAIL is strongly associated with neutrophils and is increased by IFN-gamma and alpha. BCG promoted cleavage of soluble TRAIL: from neutrophils and a Phase II trial using BCG + IFN-alpha. However, for those who have failed BCG twice, there does not seem to be benefit using the BCG-IFN-alpha. Other trials underway include adenoviral cytokine gene therapy and new gene polymorphisms that affect BCG anti-tumor response are being identified. Useful markers of BCG response are needed to help stratify patients and the basis for BCG failure needs to be better identified. This is an exciting area of research that will improve outcomes for patients in the future.
http://www.medilexicon.com/medicalnews.php?newsid=72233

Ral GTPases And Friends: New Conspirators In Bladder Cancer Metastasis And Targets For Therapy

03 Jun 2007

UroToday.com - Dr. Dan Theodorescu, University of Virginia presented "Ral GTPases and Friends: New Conspirators in Bladder Cancer Metastasis and Targets for Therapy" in the session "Target Selection in Renal Cell Carcinoma and Bladder Cancer".

Dr. Theodorescu discussed novel therapies for metastatic bladder cancer (TCC). They developed a T24 metastatic model with a subtype T24T showing in vivo metastasis while the T24 does not. Using gene Chip technology, 412 candidate metastasis promoting genes were identified. They used human primary tumors and found 451 upregulated genes. Crossing this with the genes from the animal model, 14 common genes were found.

Ral-A is a small GTPase downstream of EFGR, PI3K and RAs. It can be activated by Aurora-A and is involved in facilitating cell migration. It is activated at the protein level as well. Ral-B was not found to be upregulated in primary tumors and its protein upregulation was not associated with tumor stage, but did correlate with metastasis. Ral-B expressing tumors grew better in mice and demonstrated that knockdown of Ral-B decreased in vitro cell migration in the Boyden chamber. Metastatic disease is significantly greater in animals growing Ral-B bladder tumors. Ral-A and Ral-B were downregulated either alone or together and the genes affected by this were identified. Nine genes were identified as being significant, of which CD24 was most interesting.

CD24 is important in cell anchorage and interacts with Src, FAK and other signaling molecules. In human TCC, IHC for CD24 correlated independently as a prognostic variable. In vitro, CD24 knockdowns have decreased growth and a monoclonal antibody against CD24 is demonstrating decreased growth and metastasis in preliminary mice studies.

Ral-B, but not Ral-A is a lung metastasis promoter gene and Ral-B regulates CD24 expression. CD24 is related to human TCC metastasis and is an independent prognostic marker for TCC survival post cystectomy. Ral-B is a potential therapeutic target.
http://www.medilexicon.com/medicalnews.php?newsid=72924

Can Restaging Transurethral Resection Of T1 Bladder Cancer Select Patients For Immediate Cystectomy?

03 Jun 2007

UroToday.com- Few areas in the management of bladder cancer remain as controversial as the management of patients with tumors that invade the lamina propria without involving the muscularis propria (T1 tumors). In an attempt to help refine the selection of patients to bladder conservation versus bladder extirpation various factors have been evaluated which suggest more aggressive biologic behavior including, size, number of tumors, presence of concomitant CIS, high grade pathology, recurrent or primary tumor, presence of angiolymphatic invasion, as well as molecular markers and genetic alteration profiles.

A powerful predictor is the inherent biologic behavior of the tumor. Dr. Herr from MSKCC attempts to shed light on this variable using the re-TUR findings as a surrogate. 352 patients with T1 disease on resection by the referring urologist (only 7 patients were not 'referred') underwent re-TUR at 2-4 weeks. All received a 6 week course of BCG, none received maintenance therapy. 5 year progression rates based on findings on re-TUR were 9% for T0, 32% for Ta/CIS and 82% for T1 (p < 0. 01). Overall recurrence rates were 66%, including 58% for low grade T1 low cancers, although these tended to return later (median 27 months) and progressed less often (9% versus 38% for high grade T1 tumors).

A few points are worth emphasizing first, these patients were mostly 'referred', and at least some might not have undergone complete TUR in the first instance, second, there was a clear difference in progression rates between T1 low grade and high grade categories and lastly none of the patients received maintenance therapy.

Even with these caveats, the data suggest that patients who have high grade T1 disease on re-TUR at 2-4 weeks after primary resection should be considered to be at high risk for disease progression with conservative management and be offered early cystectomy. While it might be considered reasonable by some to wait for the results at 3 �" 6 months after therapy to make this decision, it is noteworthy that in this series among the 92 patients with residual T1 disease on re-TUR, the progression rate was 75% even if there was no evidence of tumor at 3-6 months after BCG (median time to progression 17 months). It has been shown that the prognosis of patients who undergo radical cystectomy for T1 disease is better than for those who wait until they progress to T2 disease (or greater). As such, it behooves us to continue to counsel our patients about the risks of bladder conservation more accurately, and data such as these are helpful towards that end
http://www.medilexicon.com/medicalnews.php?newsid=72911

Use Of Urinary Biomarkers For Bladder Cancer Surveillance: Patient Perspectives

03 Jun 2007

UroToday.com- Current guidelines for surveillance of bladder cancer patients include cystoscopy every 3 months for 2 years, every 6 months for 2 years and then annually. The initial compliance with this regimen was impaired by the rigid instrumentations available and urinary biomarkers were sought which might be able to supplant invasive examinations. In subsequent years, with the development of flexible cystoscopes, patient satisfaction with cystoscopy has increased. However, the belief that patients would prefer a 'urine test' to an 'invasive' cystoscopy has persisted, both among physicians and companies which develop such markers.

In the April issue of Journal of Urology, the group from Memorial Sloan Kettering Cancer Center suggests that this might not be the case. They enrolled 200 consecutive patients with a diagnosis of non muscle-invasive bladder cancer who were undergoing outpatient flexible cystoscopy. They used patient interview and the standard 'gamble method' to determine the minimal accepted diagnostic accuracy at which a urine test would be favored over cystoscopy for bladder surveillance.

The majority (54%) patients reported that they would forego a flexible cystoscopy only if the accuracy of the biomarker was 100%. An additional 16% would accept an accuracy of 99% before agreeing to supplant the cystoscopy with a biomarker. Overall, only 25% of patients would accept a urinary biomarker with an accuracy of less than 95%. This was especially noteworthy since 34% of patients had 'low-risk' disease and were aware of the low risk of tumor progression.

The authors analyzed various parameters and found that the predominant reason for refusing biomarker (75% of patients) was anxiety associated with the possibility of missing cancer. On multivariate analysis male gender (odds ratio 2.13 and pain intensity score (for every 1 point increased OR 1.25) were independently associated with a willingness to accept decreased diagnostic accuracy for the benefit of using a noninvasive assay.

Currently available biomarkers do not approach the level of accuracy demanded by patients; in fact most fall in the range of 80-90% accuracy under 'real world' conditions. Consequently, before patients are likely to accept biomarkers in place of cystoscopy, prospective, randomized trials confirming the safety of this strategy are needed.
http://www.medilexicon.com/medicalnews.php?newsid=72910

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