Bladder Cancer Survival

Bladder Cancer SurvivalDevelopmental cell biologist Philip Beachy, PhD, is the senior author of a study showing how the bladder bounces back from bacterial infection by first shedding and then regenerating several layers of cells. From our release:

The bladder is a supple, muscular organ with a well-defined task: Store urine and release it at an appropriate time. Unlike its workhorse neighbor, the intestine, it doesn’t need a lot of fussy cell division to get the job done. But when the bladder becomes infected, it launches a massive, scorched-earth attack, sloughing off the innermost layer of cells to keep invading bacteria from latching on to and burrowing into its inner lining.

“Now scientists [here] have identified the key molecular pathways that form a control circuit involved in kick-starting cell division in the bladder to repair the damage. They’ve also pinpointed what appear to be bladder stem cells critical to the repair. The research could lead to new ways to treat bladder infections and other, more deadly problems.”

The researchers, including first author, post-doc Kunyoo Shin, PhD, go on to describe how they’ve identified what seems to a bladder stem cell that facilitates the regeneration. Pinpointing such a cell and understanding how it interacts with its surroundings may lead to a greater understanding of cancers in the bladder, prostate and other similar organs, they believe.

Treatable stages of bladder cancer

Early diagnosis of cancer increases your chances of effective treatment and an optimal outcome. Know the following common warning signs of bladder cancer and see your doctor immediately if you experience any of these symptoms:

  • Blood in the urine, or hematuria (the most common symptom of bladder cancer)
  • Frequent urination in small amounts
  • Pain during urination
  • Frequent infections of the urinary tract

Other symptoms can be a sign of bladder cancer that is more advanced. These symptoms include:

  • Pain in the lower back (around the kidneys)
  • Swelling in the lower legs
  • A pelvic mass (a growth in the pelvis near the bladder)

As well, weight loss; bone pain; pain the rectal, anal, or pelvic area; and anemia can indicate that bladder cancer has spread.

If you experience any of the symptoms described above, see your doctor immediately. Other bladder conditions may cause similar symptoms, but only a doctor can determine whether or not you have bladder cancer.

Bladder-preserving Therapy

A new bladder-preserving approach to treatment of locally invasive bladder cancer appears promising, both for patients for whom radical cystectomy is indicated and for those previously ineligible for curative treatment. These findings were recently published in the International Journal of Oncology

Bladder cancerThe bladder is a hollow organ located in the pelvis. Its primary function is to store urine. The bladder has a muscular wall that allows it to get larger and smaller as urine is stored or emptied. Bladder cancer is diagnosed in roughly 50,000 men and 17,000 women annually in the United States.

Patients whose cancer has spread to deeper tissues in the bladder may be treated with a radical cystectomy, which is the surgical removal of the bladder and some nearby organs. Not all patients, however, are candidates for radical cystectomy. Alternative curative procedures for such patients are therefore needed, as are curative options that preserve the bladder.

Balloon-occluded arterial infusion (BOAI) with hemodialysis delivers a high concentration of chemotherapy (cisplatin/ Gemzar® [gemcitabine]) to the site of the tumor. By delivering anticancer agents only to the site of the tumor, other parts of the body are not adversely affected by the chemotherapy.

The current study evaluated the combination of BOAI and hemodialysis with concurrent radiation therapy. The researchers involved with the study refer to this as the “OMC” (Osaka Medical College) regimen. An important difference between the OMC regimen and radical cystectomy is that the OMC regimen does not involve removal of the bladder.

The study enrolled 192 patients with Stage T2, T3, or T4 muscle-invasive bladder cancer that had not spread to distant sites in the body. Half the patients were assigned to receive the OMC regimen, and half underwent radical cystectomy. Patients in the OMC regimen group who did not experience a complete response (CR) underwent cycstectomy or a second course of BOAI with a higher dose of chemotherapy.

  • More than 89% of patients with locally invasive tumors (T2 or T3 node-negative) on the OMC regimen experienced a CR. All but one of these 69 patients were alive with no evidence of recurrence at a median follow-up of 161 weeks. Complete responses were less common among patients with T4 or node-positive disease.
  • The five-year overall survival rate for the OMC regimen was 91.5% versus 59.8% for cystectomy.
  • The 15-year overall survival rate for the OMC regimen was 81.3% versus 40.1% for cystectomy.
  • Side effects associated with the OMC regimen were moderate.

The researchers conclude that the OMC regimen may provide a potentially curative, bladder-preserving treatment option for patients with locally invasive bladder cancer.

This regimen may be an option not only for people who would otherwise undergo radical cystectomy but also for people who are unable to tolerate radical cystectomy or conventional chemotherapy as a result of age or health problems.

Chemotherapy treatment for bladder cancer as alternative to surgery
Adding chemotherapy to radiation therapy for muscle invasive bladder cancer allows 67 percent of people to be free of disease in their bladders two years after treatment. This compares to 54 percent of people who receive radiation alone, according to the largest randomized study of its kind presented at the plenary session, November 1, 2010, at the 52nd Annual Meeting of the American Society for Radiation Oncology (ASTRO).

“The trial shows that this treatment offers improved control of cancer within the bladder with acceptable long-term side effects and is therefore a viable alternative to radical surgery in patients with muscle invasive bladder cancer,” said Nicholas James, M.D., an oncologist at University of Birmingham in Birmingham, England, United Kingdom, who jointly led the study with Robert Huddart, M.D., from the Institute of Cancer Research in the United Kingdom. “This may shift the balance from surgery to chemo-radiotherapy as the primary treatment for many patients with invasive bladder cancer.”

Bladder cancer affects about 70,000 Americans each year. It is four times more common in men than in women and two times more common in Caucasians than African-Americans. Cure rates for advanced bladder cancer are generally poor, with only around 40 percent of those with this form of the disease living more than five years after diagnosis.

In the United States, the most common treatment for advanced bladder cancer is complete removal of the bladder, which compromises patients’ normal urinary function. Radiotherapy has been used as an alternative for some time. Doctors have been making advances in combining radiation therapy and chemotherapy as a way to treat bladder cancer while allowing patients an opportunity to maintain normal bladder function.

This multicenter randomized trial, conducted at 45 institutions in the United Kingdom, examined whether adding chemotherapy to radiation treatment is safe and more effective than giving radiation alone in preventing bladder cancer from returning. The trial also compared two ways of giving radiation therapy.

From August 2001 to April 2008, 458 invasive bladder cancer patients entered the trial. Results of the study show that the combination of chemotherapy and radiation treatment reduced the long-term risk of recurrence of cancer within the bladder, while also preserving bladder function.

###

This work was supported by Cancer Research U.K. (CRUK/01/004). The trial was coordinated by the Cancer Research U.K. Clinical Trials Unit at the University of Birmingham and the Cancer Research U.K. funded Clinical Trials and Statistics Unit at the Institute of Cancer Research (ICR-CTSU) with statistical support led by Emma Hall, Ph.D., deputy director (Research), ICR.

For more information on radiation therapy for bladder cancer, visit rtanswers.org.

Selenium’s Protective Effect Against Bladder Cancer
Data from a combined analysis of previous studies suggest that higher levels of selenium are associated with lower risk of bladder cancer. These findings were recently published in the journal Cancer Epidemiology, Biomarkers & Prevention.[1]

Each year in the United States, close to 53,000 men and 18,000 women are diagnosed with bladder cancer. Many bladder cancers are thought to be caused by exposure to cancer-causing agents that pass through the urine and come into contact with the bladder lining. The most important risk factor for bladder cancer is smoking, which increases risk by at least fourfold.

Dietary supplements such as multivitamins are used by many people in the hope of reducing the risk of cancer and other diseases. Evidence that dietary supplements reduce cancer risk is limited, however, and some studies have even suggested that certain types of dietary supplements may increase cancer risk. In a recent study, the researchers found no link between vitamin C, vitamin D, or vitamin E and risk of bladder cancer.[2]

Previous studies have suggested that supplementation with the antioxidant selenium may offer a preventive effect against lung cancer and prostate cancer. However, recent studies have not confirmed these data, and according to the results of two large randomized studies, selenium and vitamin E supplements did not reduce the risk of prostate cancer.

To further explore the relationship between selenium supplementation and bladder cancer risk, researchers conducted a combined analysis of previous studies exploring levels of selenium in blood and toenails and bladder cancer risk. The data from seven previously published epidemiologic studies indicated that higher levels of selenium were associated with a lower risk of bladder cancer, particularly in women.

The researchers concluded that “although these results suggest a protective effect of selenium for bladder cancer risk, additional large studies are warranted to support [this] preliminary evidence.” There is still much to be learned about the role of nutrients in the prevention of cancer. People who are considering the use of dietary supplements such as vitamins or antioxidants are advised to discuss the risks and benefits with their physician.

Regenerating bladders by using stem cells
Researchers in the United States have developed a medical model for regenerating bladders using stem cells harvested from a patient’s own bone marrow. The research, published in STEM CELLS, is especially relevant for paediatric patients suffering from abnormally developed bladders, but also represents another step towards new organ replacement therapies.

The research, led by Dr Arun Sharma and Earl Cheng from the Feinberg School of Medicine at Northwestern University and Children’s Memorial Research Center, focused on bone marrow mesenchymal stem cells (MSCs) taken from the patient. Previously studies into the regenerative capacity of cells in bladders have focused on animal models, but these have translated poorly in clinical settings.

“Advances in the use of bone marrow stem cells taken from the patient opens up new opportunities for exploring organ replacement therapies, especially for bladder regeneration”, said senior author Sharma. “Several findings from our study have demonstrated the plasticity of stem cells derived from bone marrow which make them ideal for this type of work.”

The team discovered that bone marrow mesenchymal stem cells (MSCs) have phenotypic and physiological similarities with bladder smooth muscle cells (bSMCs) implying that MSCs can serve as an alternative cell source for potentially damaged bSMCs.

“For our research we developed a primate-based model, using the baboon bladder in conjunction with bone marrow MSCs to attempt partial bladder regeneration,” said Sharma. “We found that the mesenchymal stem cells utilized throughout the study retained the ability to populate a surgically grafted area while remaining active 10 weeks after surgery.”

The transplanted bone marrow cells also retained the ability to express key smooth muscle cell markers, attributes that are required for the continual expansion and contractile cycles of a functional bladder.

Currently information about the cellular and molecular interactions that govern bladder regeneration is scarce, however the team’s research demonstrates the feasibility of MSCs in partial bladder regeneration and their use of a primate-based mode provides valuable insight into these processes as they may apply to humans.”

“This newly described bladder augmentation model represents a unique insight into the bladder regeneration process and provides strong evidence that MSCs can be exploited for tissue engineering purposes,” concluded Sharma. “The non-human primate bladder augmentation model established in this study will also further provide key pre-clinical data that may eventually be translated in a clinical setting.”

“Bioengineering the repair of the bladder is not a simple matter. The combination of the clinical SIS material and patient supplied MSCs provides a good combination for further testing,” said Mark Pittenger, Associate Editor of STEM CELLS. “Dr. Sharma and his colleagues are advancing the pioneering work of Dr. Anthony Atala. The progress in this field in the last few years is quite promising and more clinical studies are needed.”

Full Citation: Sharma A, Bury M, Marks A, Fuller N, Meisner J, Tapaskar N, Hall L, Matoka D, Cheng E, “A Non-Human Primate Model for Urinary Bladder Regeneration Utilizing Autologous Sources of Bone Marrow Derived Mesenchymal Stem Cells”, STEM CELLS, Wiley-Blackwell, November 2010: DOI

About the Research: This work was performed in conjunction with Northwestern University Feinberg School of Medicine, Department of Urology, Children’s Memorial Hospital Division of Pediatric Urology, and the Institute for BioNanotechnology in Medicine (IBNAM) and through a generous gift from Sara C. Star

Reference:


[1] Amaral AFS, Cantor KP, Silverman DT and Malats N. Selenium and Bladder Cancer Risk: a Meta-analysis. Cancer Epidemiology, Biomarkers & Prevention [early online publication]. August 31, 2010.

[2] Hotaling J, Wright J, Pocobelli G, Porter M, White E. Risk of urothelial cell carcinoma of the bladder in the VITamins And Lifestyle study. Presented at the 2010 annual meeting of the American Urological Association. May 29-June 3, 2010. San Francisco, CA. Abstract 1162.