Bladder cancer
Encyclopedia
Bladder cancer is any of several types of malignant growths of the urinary bladder
. It is a disease in which abnormal cells multiply without control in the bladder. The bladder is a hollow, muscular organ that stores urine; it is located in the pelvis. The most common type of bladder cancer begins in cells lining the inside of the bladder and is called transitional cell carcinoma
(sometimes urothelial cell carcinoma).
) or detectable only by microscope (microscopic hematuria). Other possible symptoms include pain during urination
, frequent urination (polyuria
) or feeling the need to urinate without results. These signs and symptoms are not specific to bladder cancer, and are also caused by non-cancerous conditions, including prostate
infections and cystitis
. Kidney cancer
also can cause hematuria.
. 2-Naphthylamine
, which is found in cigarette smoke, has also been shown to increase bladder cancer risk. Occupations at risk are bus drivers, rubber workers, motor mechanics, leather (including shoe) workers, blacksmiths, machine setters and mechanics. Hairdressers are thought to be at risk as well because of their frequent exposure to permanent hair dyes. A 2008 study commissioned by the World Health Organisation concluded that "specific fruit and vegetables may act to reduce the risk of bladder cancer." Fruit and yellow-orange vegetables, particularly carrots and selenium, are probably associated with a moderately reduced risk of bladder cancer. Citrus fruits and cruciferous vegetables were also identified as having a possible protective effect.
It has been suggested that mutations at HRAS
, KRAS2, RB1, and FGFR3
may be associated in some cases.
or other physician trained in cystoscopy
, a procedure in which a flexible tube bearing a camera and various instruments is introduced into the bladder through the urethra
. Suspicious lesions may be biopsied and sent for pathologic analysis
.
The gold standard for diagnosing bladder cancer is biopsy obtained during cystoscopy
. Sometimes it is an incidental finding during cystoscopy. Urine cytology can be obtained in voided urine or at the time of the cystoscopy ("bladder washing"). Cytology is very specific (a positive result is highly indicative of bladder cancer) but suffers from low sensitivity (inability of a negative result to reliably exclude bladder cancer). There are newer non-invasive urine bound markers available as aids in the diagnosis of bladder cancer, including human complement factor H-related protein, high-molecular-weight carcinoembryonic antigen, and nuclear matrix protein 22 (NMP22). NMP22 is also available as a prescription home test.
The diagnosing of bladder cancer can also be done with a Cysview
™ guided fluorescence cystoscopy, as an adjunct to conventional white-light cystoscopy. This procedure improves the detection of bladder cancer and reduces the rate of early tumour recurrence, compared with white-light cystoscopy alone. Cysview cystoscopy detects more cancer and reduce recurrency. Cysview is marketed in Europa under the brand name Hexvix
®
. The other 10% are squamous cell carcinoma
, adenocarcinoma
, sarcoma
, small cell carcinoma
and secondary deposits from cancers elsewhere in the body.
Carcinoma in situ
(CIS) invariably consists of cytologically high grade tumour cells.
in the form of BCG instillation
is also used to treat and prevent the recurrence of superficial tumors.
BCG immunotherapy is effective in up to 2/3 of the cases at this stage. Instillations of chemotherapy
, such as valrubicin
(Valstar) into the bladder can also be used to treat BCG-refractory CIS disease when cystectomy is not an option.
Urocidin is phase III trials for this.
Patients whose tumors recurred after treatment with BCG
are more difficult to treat. Many physicians recommend Cystectomy
for these patients. This recommendation is in accordance with the official guidelines of the European Association of Urologists (EAU). and the American Urological Association (AUA) However, many patients refuse to undergo this life changing operation, and prefer to try novel conservative treatment options before opting to this last radical resort. Device assisted chemotherapy is such one group of novel technologies used to treat superficial bladder cancer. These technologies use different mechanisms to facilitate the absorption and action of a chemotherapy drug instilled directly into the bladder. Another technology uses an electrical current to enhance drug absorption. Another technology, thermotherapy, uses radio-frequency energy to directly heat the bladder wall, which together with chemotherapy shows a synergistic effect, enhancing each other's capacity to kill tumor cells. This technology was studied by different investigators.
Untreated, superficial tumors may gradually begin to infiltrate the muscular wall of the bladder. Tumors that infiltrate the bladder require more radical surgery where part or all of the bladder is removed (a cystectomy
) and the urinary stream is diverted. In some cases, skilled surgeons can create a substitute bladder (a neobladder) from a segment of intestinal tissue, but this largely depends upon patient preference, age of patient, renal function
, and the site of the disease.
A combination of radiation
and chemotherapy
can also be used to treat invasive disease. It has not yet been determined how the effectiveness of this form of treatment compares to that of radical ablative surgery.
There is weak observational evidence from one very small study (84) to suggest that the concurrent use of statin
s is associated with failure of BCG immunotherapy.
Photodynamic diagnosis may improve surgical outcome on bladder cancer.
, which is much more active in men than in women, plays a major part in the development of the cancer. Certain medications, such as the diabetes drug Actos, manufactured by Takeda Pharmaceuticals, have also been associated with the causation of bladder cancer.
Urinary bladder
The urinary bladder is the organ that collects urine excreted by the kidneys before disposal by urination. A hollow muscular, and distensible organ, the bladder sits on the pelvic floor...
. It is a disease in which abnormal cells multiply without control in the bladder. The bladder is a hollow, muscular organ that stores urine; it is located in the pelvis. The most common type of bladder cancer begins in cells lining the inside of the bladder and is called transitional cell carcinoma
Transitional cell carcinoma
Transitional cell carcinoma is a type of cancer that typically occurs in the urinary system: the kidney, urinary bladder, and accessory organs. It is the most common type of bladder cancer and cancer of the ureter, urethra, and urachus...
(sometimes urothelial cell carcinoma).
Signs and symptoms
Bladder cancer characteristically causes blood in the urine; this may be visible to the naked eye (gross hematuriaHematuria
In medicine, hematuria, or haematuria, is the presence of red blood cells in the urine. It may be idiopathic and/or benign, or it can be a sign that there is a kidney stone or a tumor in the urinary tract , ranging from trivial to lethal...
) or detectable only by microscope (microscopic hematuria). Other possible symptoms include pain during urination
Dysuria
In medicine, specifically urology, dysuria refers to painful urination.Difficult urination is also sometimes described as dysuria.It is one of a constellation of irritative bladder symptoms, which includes urinary frequency and haematuria....
, frequent urination (polyuria
Polyuria
Polyuria is a condition usually defined as excessive or abnormally large production or passage of urine . Frequent urination is sometimes included by definition, but is nonetheless usually an accompanying symptom...
) or feeling the need to urinate without results. These signs and symptoms are not specific to bladder cancer, and are also caused by non-cancerous conditions, including prostate
Prostate
The prostate is a compound tubuloalveolar exocrine gland of the male reproductive system in most mammals....
infections and cystitis
Cystitis
Cystitis is a term that refers to urinary bladder inflammation that results from any one of a number of distinct syndromes. It is most commonly caused by a bacterial infection in which case it is referred to as a urinary tract infection.-Signs and symptoms:...
. Kidney cancer
Kidney cancer
Kidney cancer is a type of cancer that starts in the cells in the kidney.The two most common types of kidney cancer are renal cell carcinoma and urothelial cell carcinoma of the renal pelvis...
also can cause hematuria.
Causes
Tobacco smoking is the main known contributor to urinary bladder cancer; in most populations, smoking is associated with over half of bladder cancer cases in men and one-third of cases among women. There is a linear relationship between smoking and risk, and quitting smoking reduces the risk. Passive smoking has not been proven to be involved. In a 10-year study involving almost 48,000 men, researchers found that men who drank 1.5L of water a day had a significantly reduced incidence of bladder cancer when compared with men who drank less than 240mL (around 1 cup) per day. The authors proposed that bladder cancer might partly be caused by the bladder directly contacting carcinogens that are excreted in urine, although this has not yet been confirmed in other studies. Thirty percent of bladder tumors probably result from occupational exposure in the workplace to carcinogens such as benzidineBenzidine
Benzidine, the trivial name for 4,4'-diaminobiphenyl, is the solid organic compound with the formula 2. This aromatic amine is a component of a test for cyanide and also in the production of dyes...
. 2-Naphthylamine
2-Naphthylamine
2-Naphthylamine is an aromatic amine. It is used to make azo dyes. It is a known human carcinogen and has largely been replaced by less toxic compounds. 2-Naphthylamine is prepared by heating 2-naphthol with ammonium zinc chloride to 200-210 °C; or in the form of its acetyl derivative by heating...
, which is found in cigarette smoke, has also been shown to increase bladder cancer risk. Occupations at risk are bus drivers, rubber workers, motor mechanics, leather (including shoe) workers, blacksmiths, machine setters and mechanics. Hairdressers are thought to be at risk as well because of their frequent exposure to permanent hair dyes. A 2008 study commissioned by the World Health Organisation concluded that "specific fruit and vegetables may act to reduce the risk of bladder cancer." Fruit and yellow-orange vegetables, particularly carrots and selenium, are probably associated with a moderately reduced risk of bladder cancer. Citrus fruits and cruciferous vegetables were also identified as having a possible protective effect.
It has been suggested that mutations at HRAS
HRAS
GTPase HRas also known as transforming protein p21 is an enzyme that in humans is encoded by the HRAS gene. The HRAS gene is located on the short arm of chromosome 11 at position 15.5, from base pair 522,241 to base pair 525,549.- Function :...
, KRAS2, RB1, and FGFR3
FGFR3
Fibroblast growth factor receptor 3 is a protein that in humans is encoded by the FGFR3 gene. FGFR3 has also been designated as CD333 .-Structure and function:-Disease linkage:...
may be associated in some cases.
Diagnosis
Many patients with a history, signs, and symptoms suspicious for bladder cancer are referred to a urologistUrology
Urology is the medical and surgical specialty that focuses on the urinary tracts of males and females, and on the reproductive system of males. Medical professionals specializing in the field of urology are called urologists and are trained to diagnose, treat, and manage patients with urological...
or other physician trained in cystoscopy
Cystoscopy
Cystoscopy is endoscopy of the urinary bladder via the urethra. It is carried out with a cystoscope.Diagnostic cystoscopy is usually carried out with local anaesthesia...
, a procedure in which a flexible tube bearing a camera and various instruments is introduced into the bladder through the urethra
Urethra
In anatomy, the urethra is a tube that connects the urinary bladder to the genitals for the removal of fluids out of the body. In males, the urethra travels through the penis, and carries semen as well as urine...
. Suspicious lesions may be biopsied and sent for pathologic analysis
Surgical pathology
Surgical pathology is the most significant and time-consuming area of practice for most anatomical pathologists. Surgical pathology involves the gross and microscopic examination of surgical specimens, as well as biopsies submitted by non-surgeons such as general internists, medical subspecialists,...
.
The gold standard for diagnosing bladder cancer is biopsy obtained during cystoscopy
Cystoscopy
Cystoscopy is endoscopy of the urinary bladder via the urethra. It is carried out with a cystoscope.Diagnostic cystoscopy is usually carried out with local anaesthesia...
. Sometimes it is an incidental finding during cystoscopy. Urine cytology can be obtained in voided urine or at the time of the cystoscopy ("bladder washing"). Cytology is very specific (a positive result is highly indicative of bladder cancer) but suffers from low sensitivity (inability of a negative result to reliably exclude bladder cancer). There are newer non-invasive urine bound markers available as aids in the diagnosis of bladder cancer, including human complement factor H-related protein, high-molecular-weight carcinoembryonic antigen, and nuclear matrix protein 22 (NMP22). NMP22 is also available as a prescription home test.
The diagnosing of bladder cancer can also be done with a Cysview
Cysview
Cysview is an optical imaging agent designed to enhance detection of bladder cancer, in particular carcinoma in situ , it reveals lesions that may not be seen with standard white light cystoscopy. Cysview is marketed in Europe as Hexvix...
™ guided fluorescence cystoscopy, as an adjunct to conventional white-light cystoscopy. This procedure improves the detection of bladder cancer and reduces the rate of early tumour recurrence, compared with white-light cystoscopy alone. Cysview cystoscopy detects more cancer and reduce recurrency. Cysview is marketed in Europa under the brand name Hexvix
Hexvix
Hexvix is an optical imaging agent developed by the Norwegian pharmaceutical company Photocure ASA. Hexvix is designed to enhance detection of bladder cancer, in particular carcinoma in situ , it reveals lesions that may not be seen with standard white light cystoscopy...
®
Pathological classification
90% of bladder cancers are Transitional cell carcinomaTransitional cell carcinoma
Transitional cell carcinoma is a type of cancer that typically occurs in the urinary system: the kidney, urinary bladder, and accessory organs. It is the most common type of bladder cancer and cancer of the ureter, urethra, and urachus...
. The other 10% are squamous cell carcinoma
Squamous cell carcinoma
Squamous cell carcinoma , occasionally rendered as "squamous-cell carcinoma", is a histologically distinct form of cancer. It arises from the uncontrolled multiplication of malignant cells deriving from epithelium, or showing particular cytological or tissue architectural characteristics of...
, adenocarcinoma
Adenocarcinoma
Adenocarcinoma is a cancer of an epithelium that originates in glandular tissue. Epithelial tissue includes, but is not limited to, the surface layer of skin, glands and a variety of other tissue that lines the cavities and organs of the body. Epithelium can be derived embryologically from...
, sarcoma
Sarcoma
A sarcoma is a cancer that arises from transformed cells in one of a number of tissues that develop from embryonic mesoderm. Thus, sarcomas include tumors of bone, cartilage, fat, muscle, vascular, and hematopoietic tissues...
, small cell carcinoma
Small cell carcinoma
Small cell carcinoma is a type of highly malignant cancer that most commonly arises within the lung, although it can occasionally arise in other body sites, such as the cervix and prostate....
and secondary deposits from cancers elsewhere in the body.
Carcinoma in situ
Carcinoma in situ
Carcinoma in situ is an early form of cancer that is defined by the absence of invasion of tumor cells into the surrounding tissue, usually before penetration through the basement membrane. In other words, the neoplastic cells proliferate in their normal habitat, hence the name "in situ"...
(CIS) invariably consists of cytologically high grade tumour cells.
Staging
The following stages are used to classify the location, size, and spread of the cancer, according to the TNM (tumor, lymph node, and metastasis) staging system:- Stage 0: Cancer cells are found only on the inner lining of the bladder (This stage is also often called Stage Ta).
- Stage I: Cancer cells have proliferated to the layer beyond the inner lining of the urinary bladder but not to the muscles of the urinary bladder.
- Stage II: Cancer cells have proliferated to the muscles in the bladder wall but not to the fatty tissue that surrounds the urinary bladder.
- Stage III: Cancer cells have proliferated to the fatty tissue surrounding the urinary bladder and to the prostate gland, vagina, or uterus, but not to the lymph nodes or other organs.
- Stage IV: Cancer cells have proliferated to the lymph nodes, pelvic or abdominal wall, and/or other organs.(Most common lymph node involved is Hypogastric lymph node.)
- Recurrent: Cancer has recurred in the urinary bladder or in another nearby organ after having been treated.
Screening
As of 2010 there is insufficient evidence to determine if screening for bladder cancer in people without symptoms is effective or not.Treatment
The treatment of bladder cancer depends on how deep the tumor invades into the bladder wall. Superficial tumors (those not entering the muscle layer) can be "shaved off" using an electrocautery device attached to a cystoscope. ImmunotherapyImmunotherapy
Immunotherapy is a medical term defined as the "treatment of disease by inducing, enhancing, or suppressing an immune response". Immunotherapies designed to elicit or amplify an immune response are classified as activation immunotherapies. While immunotherapies that reduce or suppress are...
in the form of BCG instillation
BCG as a treatment for bladder cancer
BCG , a live attenuated form of Mycobacterium bovis, is the most commonly used agent for intravesical therapy. A number of other intravesical agents have been compared to BCG, but none has proved consistently superior....
is also used to treat and prevent the recurrence of superficial tumors.
BCG immunotherapy is effective in up to 2/3 of the cases at this stage. Instillations of chemotherapy
Chemotherapy
Chemotherapy is the treatment of cancer with an antineoplastic drug or with a combination of such drugs into a standardized treatment regimen....
, such as valrubicin
Valrubicin
Valrubicin is a chemotherapy drug used to treat bladder cancer. Valrubicin is a semisynthetic analog of the anthracycline doxorubicin, and is administered by infusion directly into the bladder.It was originally launched as Valstar in the U.S...
(Valstar) into the bladder can also be used to treat BCG-refractory CIS disease when cystectomy is not an option.
Urocidin is phase III trials for this.
Patients whose tumors recurred after treatment with BCG
BCG
BCG can stand for:Medicine*Bacillus Calmette-Guérin, a vaccine for tuberculosis*Ballistocardiography, a vital sign caused by the mechanical movement of the heart which can be recorded from the surface of the bodyBusiness...
are more difficult to treat. Many physicians recommend Cystectomy
Cystectomy
Cystectomy is a medical term for surgical removal of all or part of the urinary bladder. It may also be rarely used to refer to the removal of a cyst, or the gallbladder. The most common condition warranting removal of the urinary bladder is bladder cancer. After the bladder has been removed, an...
for these patients. This recommendation is in accordance with the official guidelines of the European Association of Urologists (EAU). and the American Urological Association (AUA) However, many patients refuse to undergo this life changing operation, and prefer to try novel conservative treatment options before opting to this last radical resort. Device assisted chemotherapy is such one group of novel technologies used to treat superficial bladder cancer. These technologies use different mechanisms to facilitate the absorption and action of a chemotherapy drug instilled directly into the bladder. Another technology uses an electrical current to enhance drug absorption. Another technology, thermotherapy, uses radio-frequency energy to directly heat the bladder wall, which together with chemotherapy shows a synergistic effect, enhancing each other's capacity to kill tumor cells. This technology was studied by different investigators.
Untreated, superficial tumors may gradually begin to infiltrate the muscular wall of the bladder. Tumors that infiltrate the bladder require more radical surgery where part or all of the bladder is removed (a cystectomy
Cystectomy
Cystectomy is a medical term for surgical removal of all or part of the urinary bladder. It may also be rarely used to refer to the removal of a cyst, or the gallbladder. The most common condition warranting removal of the urinary bladder is bladder cancer. After the bladder has been removed, an...
) and the urinary stream is diverted. In some cases, skilled surgeons can create a substitute bladder (a neobladder) from a segment of intestinal tissue, but this largely depends upon patient preference, age of patient, renal function
Renal function
Renal function, in nephrology, is an indication of the state of the kidney and its role in renal physiology. Glomerular filtration rate describes the flow rate of filtered fluid through the kidney...
, and the site of the disease.
A combination of radiation
Radiation
In physics, radiation is a process in which energetic particles or energetic waves travel through a medium or space. There are two distinct types of radiation; ionizing and non-ionizing...
and chemotherapy
Chemotherapy
Chemotherapy is the treatment of cancer with an antineoplastic drug or with a combination of such drugs into a standardized treatment regimen....
can also be used to treat invasive disease. It has not yet been determined how the effectiveness of this form of treatment compares to that of radical ablative surgery.
There is weak observational evidence from one very small study (84) to suggest that the concurrent use of statin
Statin
Statins are a class of drugs used to lower cholesterol levels by inhibiting the enzyme HMG-CoA reductase, which plays a central role in the production of cholesterol in the liver. Increased cholesterol levels have been associated with cardiovascular diseases, and statins are therefore used in the...
s is associated with failure of BCG immunotherapy.
Photodynamic diagnosis may improve surgical outcome on bladder cancer.
Epidemiology
In the United States, bladder cancer is the fourth most common type of cancer in men and the ninth most common cancer in women. More than 50,000 men and 16,000 women are diagnosed with bladder cancer each year. Smoking can only partially explain this higher incidence. One other reason is that the androgen receptorAndrogen receptor
The androgen receptor , also known as NR3C4 , is a type of nuclear receptor that is activated by binding of either of the androgenic hormones testosterone or dihydrotestosterone in the cytoplasm and then translocating into the nucleus...
, which is much more active in men than in women, plays a major part in the development of the cancer. Certain medications, such as the diabetes drug Actos, manufactured by Takeda Pharmaceuticals, have also been associated with the causation of bladder cancer.
External links
- Clinically reviewed bladder cancer information for patients, from Cancer Research UKCancer Research UKCancer Research UK is a cancer research and awareness charity in the United Kingdom, formed on 4 February 2002 by the merger of The Cancer Research Campaign and the Imperial Cancer Research Fund. Its aim is to reduce the number of deaths from cancer. As the world's largest independent cancer...
- UK bladder cancer statistics from Cancer Research UKCancer Research UKCancer Research UK is a cancer research and awareness charity in the United Kingdom, formed on 4 February 2002 by the merger of The Cancer Research Campaign and the Imperial Cancer Research Fund. Its aim is to reduce the number of deaths from cancer. As the world's largest independent cancer...
- Cancer.Net: Bladder Cancer