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Glossary


Research and development in bladder cancer

Our knowledge of cancer is always expanding. Researchers and healthcare professionals take the knowledge gained from research studies and use it to develop better practices that will help prevent, detect and treat bladder cancer, as well as improve the quality of life of people with bladder cancer.

 

The following information is a selection of research showing promise for bladder cancer.

Risk reduction

Risk reduction strategies may reduce the chance of developing cancer.

 

Noteworthy research includes:

  • Some research shows that drinking or eating large amounts of milk and dairy products may lower the risk of bladder cancer. More research is still needed to clarify the effect milk and dairy products may have on bladder cancer risk (Nutrition and Cancer, PMID* 22043867).
  • Arsenic is a known risk factor for bladder cancer. It naturally occurs in rocks and soil, and it may be found in some drinking water. Reducing exposure to arsenic by treating contaminated water supplies has lowered the incidence of bladder cancer in those communities (Cancer Causes & Control, PMID 21052815).
  • Selenium is a mineral that plays an important role in many body functions. It is naturally found in some plants and animals that we eat. Some research suggests that selenium may be associated with a lower risk of bladder cancer. A large randomized controlled phase III trial in Belgium, called SELEBLAT, is hoping to find out if selenium supplements can lower the risk of bladder cancer coming back (recurring) (BMC Urology, PMID 22436453).
  • Women who have given birth may have a lower risk of bladder cancer than women who haven’t given birth. More research is needed to find out how hormones and reproductive history may be linked to bladder cancer (Cancer, Epidemiology, Biomarkers & Prevention, PMID 21493870; European Journal of Cancer, PMID 21067913).

Early detection

Researchers are working to improve early detection techniques for bladder cancer so that it can be found early, before someone notices signs and symptoms.

 

Noteworthy research includes:

  • Researchers are looking at tumour markers in urine that will help find bladder cancer early. Tumour markers are proteins or other substances that indicate cancer cells may be present. Researchers are studying many different tumour markers, both alone and together. Some of these tumour markers include:
    • survivin mRNA
    • bladder tumour–associated antigen (BTA)
    • vascular endothelial growth factor  (VEGF)
    • nuclear matrix protein 22 (NMP22)
    • minichromosome maintenance complex component 5 (MCM5)
    • uroplakin 3A (UPK3A)
    • urinary soluble Met (sMet)
    • growth differentiation factor 15 (GDF15), transmembrane protein with EGF-like and two follistatin-like domains 2 (TMEFF2) and Vimentin (VIM) are being studied in combination

 

Until now, none of these markers have proven effective enough at finding bladder cancer. They may miss finding a tumour or they may suggest there is a tumour when there actually is no tumour. Some of the markers show promise, but more research is needed to find out which markers most accurately find bladder cancer early (PloS One, PMID 22792272, PMID 22530010; Urology, PMID 22386755, PMID 20579701, PMID 20346489; BJU International, PMID 22313585; ASCO** Abstract 257; Journal of Urology, PMID 20006858, PMID 19450825; Clinical Cancer Research, PMID 20975101).

Diagnosis

A key area of research involves developing better ways to diagnose and stage bladder cancer.

 

Noteworthy research includes:

  • Tumour markers in urine may help diagnose bladder cancer and find recurrence in people previously treated for the disease. Tumour markers are proteins or other substances that indicate cancer cells may be present. The most established urine tumour markers include bladder tumour–associated antigen (BTA), hyaluronidase and nuclear matrix protein 22 (NMP22) (Urologic Oncology, PMID 20610281; Journal of Urology, PMID 20006858). Researchers are also studying other tumour markers in urine to see if they can help detect bladder cancer or bladder cancer recurrence (World Journal of Urology, PMID 21739120; Medical Oncology, PMID 21611839; Anticancer Research, PMID 19846987). As with the use of tumour markers for early detection, more research is needed to determine the role tumour markers in urine will play in diagnosis and follow-up for recurrence.
  • Gene expression profiling is a promising way to diagnose many types of cancer. It allows doctors to analyze many genes to try to identify which ones are linked to a particular type of cancer. Researchers are doing gene expression profiling on cells in urine as a way to find bladder cancer and help determine prognosis (Clinical Cancer Research, PMID 20406841).
  • MicroRNA is short, single-stranded RNA. It is thought to regulate the expression of genes. The make-up of microRNA is changed in cancer cells compared to normal cells. Canadian and international researchers have found that testing for microRNA in urine samples may help diagnose bladder cancer (British Journal of Cancer, PMID 22644299; Canadian Urological Association Journal, PMID 22630336).
  • Fluorescence in situ hybridization(FISH) is used to find abnormal chromosomes and other genetic changes in cancer cells. FISH uses special DNA probes labelled with fluorescent dyes. It can identify changes specific to bladder cancer in cells in the urine. FISH may also be useful in finding recurrence of bladder cancer and monitoring response to bacillus Calmette-Guérin (BCG) therapy (Urologic Oncology, PMID 22621963; Journal of Urology, PMID 22245325, PMID 19913822; Cancer Cytopathology, PMID 21717592; Cancer Genetics and Cytogenetics, PMID 20362229).
  • Virtual cystoscopy uses computed tomography (CT) or magnetic resonance imaging (MRI) to make images of the bladder. A virtual cystoscopy is less invasive and more comfortable than a regular cystoscopy, which involves inserting a cystoscope through the urethra (Abdominal Imaging, PMID 22623028, PMID 19471998; Urology, PMID 22310741; Journal of Computer Assisted Tomography, PMID 20118734). Researchers have found that CT virtual cystoscopy was a better diagnostic tool than MRI virtual cystoscopy (European Journal of Radiology, PMID 20452159). Researchers are still studying virtual cystoscopy and it is not routinely available. Regular cystoscopy remains the standard test for finding bladder cancer.
  • Researchers are looking at a special technique called narrow-band imaging cystoscopy to see if it improves the diagnosis of bladder cancer that has not spread to the muscle layer. Narrow-band imaging allows the doctor doing the cystoscopy to see blood vessels and other structures in the lining of the bladder better than with regular “white light” cystoscopy (Urology, PMID 22342408, PMID 20223505; Urologic Oncology, PMID 22079940). Researchers have found that narrow-band imaging cystoscopy is better at finding recurrent bladder tumours and any tumour left behind following surgery (residual tumour), compared to white light cystoscopy (BJU International, PMID 20707789, PMID 19549255).

Prognostic factors

Prognostic factors that may help determine the outcome of the disease are being studied in bladder cancer. They can be used to predict the chances of recovery or of cancer coming back. Doctors may also use prognostic factors to help them make treatment recommendations.

 

Noteworthy research includes:

  • The presence of bladder cancer cells in blood or lymph vessels is called lymphovascular invasion (LVI). In people who have undergone a radical cystectomy (surgery to remove the bladder), those with LVI had lower survival and higher rates of recurrence than people without LVI. The presence of LVI may help determine the course of treatment for people with bladder cancer (Anticancer Research, PMID 21965769; BJU International, PMID 20880163, PMID 20132195, PMID 20067452).
  • Nodal density is the number of lymph nodes that contain cancer cells compared to the total number of lymph nodes removed during surgery. Researchers have found that, in people with bladder cancer, the more lymph nodes removed and the lower the nodal density, the better the prognosis (BJU International, PMID 22758775; Urologic Oncology, PMID 21478035; European Urology, PMID 21296488).
  • Surgical margins are the cut edges of tissue around the tumour after it has been removed with surgery. Positive surgical margins contain cancer cells. Studies show that positive surgical margins are linked to a higher risk of recurrence and a less favourable prognosis in people with bladder cancer (BJU International, PMID 22578156; Journal of Urology, PMID 20399473, PMID 19942232).
  • Researchers are studying many different tumour markers that will help predict prognosis for people with bladder cancer (Current Opinion in Urology, PMID 21814055). Tumour markers are certain proteins or other substances in bladder cancer cells that indicate the cancer may be more aggressive, more likely to recur, or more or less likely to respond to chemotherapy. Some of the tumour markers that researchers are studying include:
    • phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA)
    • heme oxygenase 1 (HMOX1)
    • multidrug resistance protein 1 (MDR1)
    • excision repair cross-complementing rodent repair deficiency, complementation group 1 (ERCC1)
    • topoisomerase-II alpha (TOP2A)

 

As with the use of tumour markers for early detection and diagnosis, more research is needed to determine the role tumour markers will play in predicting prognosis for people with bladder cancer (ASCO, Abstract 4584; BMC Cancer, PMID 22616552; Journal of Urology, PMID 21168882; Neoplasia, PMID 20689757; Urology, PMID 19913893).

  • A study found that poor nutrition was a strong predictor of poor overall survival in people with bladder cancer who had a radical cystectomy (the entire bladder removed) (Journal of Urology, PMID 21074802). Poor nutrition included weight loss before surgery, a low body mass index (BMI) and low levels of protein (albumin) in the blood. More research is needed to find out whether improving a person’s nutrition will help improve the prognosis.

Treatment

Researchers are looking for new ways to improve the treatment of bladder cancer. Advances in cancer treatment and new ways to manage the side effects related to treatment have improved the outlook and quality of life for many people with cancer.

 

Noteworthy research includes:

  • Laparoscopic cystectomy is a procedure that removes the bladder using a laparoscope inserted through small incisions. Surgeons may remove the bladder this way instead of doing an open radical cystectomy, which requires a large incision. Laparoscopic cystectomy is more complicated to do, but its advantages include a shorter recovery time, less blood loss and fewer blood transfusions compared to open surgery. Research to date shows that laparoscopic cystectomy is as safe as the standard open surgery technique (International Journal of Clinical Practice, PMID 22507234; International Journal of Urology, PMID 19930499).
  • Researchers are studying robotic-assisted radical cystectomy, a type of laparoscopic cystectomy, in people with bladder cancer. The surgeon doing the operation sits near the operating table and controls robotic arms that remove the bladder through several small incisions in the abdomen. Like laparoscopic cystectomy, robotic-assisted radical cystectomy is more complicated than open radical cystectomy, but its advantages include a shorter recovery time, less blood loss and fewer blood transfusions. Some studies have reported a better outcome in people over the age of 70, so they may benefit most from it (Journal of Endourology, PMID 22788707, PMID 22582706; Urology, PMID 22516354; International Journal of Clinical Practice, PMID 22507234; Journal of Urology, PMID 20006884; BJU International, PMID 19903170). This type of surgery has become common for removing the prostate. The technology of wristed instruments (the tips of the instruments turn and bend like the human wrist) makes this approach easier than the laparoscopic approach. When the robotic approach was first used, doctors worried about the possibility of leaving behind microscopic areas of cancer. However, researchers have found that robotic-assisted radical cystectomy is not associated with a higher risk of positive surgical margins (cancer cells in the margin of tissue removed during surgery) (Journal of Urology, PMID 20478596). Urinary diversion is usually performed through an open incision, but doctors are also doing this procedure with robotic surgery (Canadian Journal of Urology, PMID 21333051; European Urology, PMID 20079567). Researchers found that robotic-assisted lymph node removal has the same success rate as other surgery methods (Urology, PMID 20350755, PMID 20110111).
  • Because a radical cystectomy removes the entire bladder, researchers continue to look for approaches to treatment that spare the bladder (bladder-sparing techniques). Conservation therapy may be an option for certain people with bladder cancer that has spread to the muscle layer. A combined approach that uses transurethral resection, chemotherapy and radiation therapy may be as effective for long-term control of bladder cancer as radical cystectomy (New England Journal of Medicine, PMID 22512481; Anticancer Research, PMID 21498726). Researchers are still studying this approach and who may benefit most from it.
  • Intravesical chemotherapy is a form of chemotherapy that gives the drug directly into the bladder. Researchers are studying gemcitabine (Gemzar) and valrubicin (Valstar) intravesical chemotherapy to see how effective these drugs may be for treating superficial bladder cancer that stops responding or becomes resistant (refractory) to bacillus Calmette-Guérin (BCG) (Urologic Oncology, PMID 22575238; Cancer, PMID 20162706). A phase III trial found that people with recurrent superficial bladder cancer who were given intravesical gemcitabine remained free of cancer longer than those who were given intravesical mitomycin (Mutamycin) after BCG treatment stopped working (Journal of Clinical Oncology, PMID 19841330).
  • Researchers are trying to find out if using an electrical current during drug delivery can make chemotherapy given directly into the bladder (intravesical chemotherapy) work better for early cancer. Chemotherapy given in combination with an electrical current is called electromotive drug administration (EMDA). EMDA may make it easier for the bladder lining to absorb the chemotherapy drug (ASCO, Abstract 4572; Lancet Oncology, PMID 21831711).
  • Thermochemotherapy involves heating the drug before giving it as intravesical chemotherapy. A study suggested that adjuvant thermochemotherapy with mitomycin C for bladder cancer that has not grown into the muscle of the bladder (non-invasive) may provide long-term control of bladder tumours (BJU International, PMID 21029314).
  • Vinflunine (Javlor) is a vinca alkaloid drug related to vinblastine (Velbe), which is used to treat bladder cancer. In a phase III trial for people with metastatic bladder cancer that progressed after treatment with cisplatin (Platinol AQ), vinflunine combined with supportive care improved survival when compared to supportive care alone (Expert Review of Anticancer Therapy, PMID 21166506; Drugs, PMID 20568834).
  • A phase II trial found that the combination of bevacizumab (Avastin), gemcitabine (Gemzar) and cisplatin (Platinol AQ) may be a promising treatment option for people with metastatic bladder cancer (Journal of Clinical Oncology, PMID 21422406).
  • A low oxygen level in cancer cells (hypoxia) is one of the factors that can make a tumour resistant to radiation treatment. Carbogen and nicotinamide can improve oxygen levels in cancer cells. Researchers are combining radiation with carbogen and nicotinamide to try to improve response to radiation therapy in people with bladder cancer (Journal of Clinical Oncology, PMID 20956620).

Supportive care

Living with cancer can be challenging in many different ways. Supportive care can help people cope with cancer, its treatment and possible side effects.

 

Noteworthy research includes:

  • Treatments that preserve the bladder (bladder-sparing approaches), such as chemotherapy or radiation therapy, may have a positive effect on the quality of life of people treated for bladder cancer (Canadian Journal of Oncology Nursing, PMID  21171541; International Journal of Radiation Oncology, Biology Physics, PMID 20385453).

 

*PMID is the US National Library of Medicine PubMed abstract identity number.

**ASCO is the American Society of Clinical Oncology.

 

Find out more about the research process.

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