Bladder cancer is the
abnormal growth of cells in the
bladder
The bladder () is a hollow organ in humans and other vertebrates that stores urine from the kidneys. In placental mammals, urine enters the bladder via the ureters and exits via the urethra during urination. In humans, the bladder is a distens ...
. These cells can grow to form a
tumor
A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...
, which eventually spreads, damaging the bladder and other organs. Most people with bladder cancer are diagnosed after noticing
blood in their urine. Those suspected of having bladder cancer typically have their bladder inspected by a thin medical camera, a procedure called
cystoscopy
Cystoscopy is endoscopy of the urinary bladder via the urethra. It is carried out with a cystoscope.
The urethra is the tube that carries urine from the bladder to the outside of the body.
The cystoscope has lenses like a telescope or microscop ...
. Suspected tumors are removed and examined to determine if they are cancerous. Based on how far the tumor has spread, the cancer case is assigned a
stage
Stage, stages, or staging may refer to:
Arts and media Acting
* Stage (theatre), a space for the performance of theatrical productions
* Theatre, a branch of the performing arts, often referred to as "the stage"
* ''The Stage'', a weekly Brit ...
0 to 4; a higher stage indicates a more widespread and dangerous disease.
Those whose bladder tumors have not spread outside the bladder have the best prognoses. These tumors are typically surgically removed, and the person is treated with
chemotherapy
Chemotherapy (often abbreviated chemo, sometimes CTX and CTx) is the type of cancer treatment that uses one or more anti-cancer drugs (list of chemotherapeutic agents, chemotherapeutic agents or alkylating agents) in a standard chemotherapy re ...
or one of several immune-stimulating therapies. Those whose tumors continue to grow, or whose tumors have penetrated the bladder muscle, often have their bladder surgically removed (
radical 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. The most common condition warranting removal of the urinary bladder is bladder cancer.
Two mai ...
). People whose tumors have spread beyond the bladder have the worst prognoses; on average they survive a year from diagnosis. These people are treated with chemotherapy and
immune checkpoint inhibitors, followed by
enfortumab vedotin.
Around 500,000 people are diagnosed with bladder cancer each year, and 200,000 die of the disease. The risk of bladder cancer increases with age and the average age at diagnosis is 73.
Tobacco smoking
Tobacco smoking is the practice of burning tobacco and ingesting the resulting smoke. The smoke may be inhaled, as is done with cigarettes, or released from the mouth, as is generally done with pipes and cigars. The practice is believed to hav ...
is the greatest contributor to bladder cancer risk, and causes around half of bladder cancer cases. Exposure to certain toxic chemicals or the tropical bladder infection
schistosomiasis
Schistosomiasis, also known as snail fever, bilharzia, and Katayama fever is a neglected tropical helminthiasis, disease caused by parasitism, parasitic Schistosoma, flatworms called schistosomes. It affects both humans and animals. It affects ...
also increases the risk.
Signs and symptoms

The most common symptom of bladder cancer is visible
blood in the urine
Hematuria or haematuria is defined as the presence of blood or red blood cells in the urine. "Gross hematuria" occurs when urine appears red, brown, or tea-colored due to the presence of blood. Hematuria may also be subtle and only detectable with ...
(haematuria) despite painless urination. This affects around 75% of people eventually diagnosed with the disease. Some instead have "microscopic haematuria" – small amounts of blood in the urine that can only be seen under a microscope during
urinalysis
Urinalysis, a portmanteau of the words ''urine'' and ''analysis'', is a Test panel, panel of medical tests that includes physical (macroscopic) examination of the urine, chemical evaluation using urine test strips, and #Microscopic examination, m ...
– pain while urinating, or no symptoms at all (their tumors are detected during unrelated
medical imaging
Medical imaging is the technique and process of imaging the interior of a body for clinical analysis and medical intervention, as well as visual representation of the function of some organs or tissues (physiology). Medical imaging seeks to revea ...
). Less commonly, a tumor can block the flow of urine into the bladder; backed up urine can cause the
kidneys to swell resulting in pain along the flank of the body between the ribs and the hips. Most people with blood in the urine do not have bladder cancer; up to 22% of those with visible haematuria and 5% with microscopic haematuria are diagnosed with the disease. Women with bladder cancer and haematuria are often misdiagnosed with
urinary tract infection
A urinary tract infection (UTI) is an infection that affects a part of the urinary tract. Lower urinary tract infections may involve the bladder (cystitis) or urethra (urethritis) while upper urinary tract infections affect the kidney (pyel ...
s, delaying appropriate diagnosis and treatment.
Around 3% of people with bladder cancer have tumors that have already spread (metastasized) outside the bladder at the time of diagnosis. Bladder cancer most commonly spreads to the bones, lungs, liver, and nearby
lymph node
A lymph node, or lymph gland, is a kidney-shaped organ of the lymphatic system and the adaptive immune system. A large number of lymph nodes are linked throughout the body by the lymphatic vessels. They are major sites of lymphocytes that includ ...
s. Tumors cause different symptoms in each location. People whose cancer has metastasized to the bones most often experience bone pain or bone weakness that increases the risk of
fractures
Fracture is the appearance of a crack or complete separation of an object or material into two or more pieces under the action of stress (mechanics), stress. The fracture of a solid usually occurs due to the development of certain displacemen ...
. Lung tumors can cause persistent cough,
coughing up blood, breathlessness, or recurrent chest infections. Cancer that has spread to the liver can cause general
malaise
In medicine, malaise is a feeling of general discomfort, uneasiness or lack of wellbeing and often the first sign of an infection or other disease. It is considered a vague termdescribing the state of simply not feeling well. The word has exist ...
, loss of appetite, weight loss, abdominal pain or
swelling,
jaundice
Jaundice, also known as icterus, is a yellowish or, less frequently, greenish pigmentation of the skin and sclera due to high bilirubin levels. Jaundice in adults is typically a sign indicating the presence of underlying diseases involving ...
(yellowing of the skin and eyes), and skin itch. Spreading to nearby lymph nodes can cause pain and swelling around the affected lymph nodes, typically in the abdomen or groin.
Diagnosis
Those suspected of having bladder cancer undergo several tests to assess the presence and extent of any tumors. The
gold standard
A gold standard is a backed currency, monetary system in which the standard economics, economic unit of account is based on a fixed quantity of gold. The gold standard was the basis for the international monetary system from the 1870s to the ...
is
cystoscopy
Cystoscopy is endoscopy of the urinary bladder via the urethra. It is carried out with a cystoscope.
The urethra is the tube that carries urine from the bladder to the outside of the body.
The cystoscope has lenses like a telescope or microscop ...
, wherein a flexible camera is threaded through the
urethra
The urethra (: urethras or urethrae) is the tube that connects the urinary bladder to the urinary meatus, through which Placentalia, placental mammals Urination, urinate and Ejaculation, ejaculate.
The external urethral sphincter is a striated ...
and into the bladder to visually inspect for cancerous tissue.
[ Cystoscopy is most efficient at detecting papillary tumors (tumors with a finger-like shape that grow into the urine-holding part of the bladder); it is less efficient with small, low-lying ]carcinoma in situ
Carcinoma ''in situ'' (CIS) is a group of abnormal cells. While they are a form of neoplasm, there is disagreement over whether CIS should be classified as cancer. This controversy also depends on the exact CIS in question (e.g., cervical, skin, b ...
(CIS). CIS detection is improved by blue light cystoscopy, where a dye ( hexaminolevulinate) that accumulates in cancer cells is injected into the bladder during cystoscopy. The dye fluoresces when the cystoscope shines blue light on it, allowing for more accurate detection of small tumors.[
]
Suspected tumors are removed during cystoscopy in a procedure called "transurethral resection of bladder tumor" (TURBT). All tumors are removed, as well as a piece of the underlying bladder muscle. Removed tissue is examined by a pathologist to determine if it is cancerous.[ If the tumor is removed incompletely, or is determined to be particularly high risk, a repeat TURBT is performed 4 to 6 weeks later to detect and remove any additional tumors.
Several non-invasive tests are available to support the diagnosis. First, many undergo a physical examination that can involve a ]digital rectal exam
Digital rectal examination (DRE), also known as a prostate exam (), is an internal examination of the rectum performed by a healthcare provider.
Prior to a 2018 report from the United States Preventive Services Task Force, a digital exam was a c ...
and pelvic exam
A pelvic examination is the physical examination of the external and internal female pelvic organs. It is frequently used in gynecology for the evaluation of symptoms affecting the female reproductive and urinary tract, such as pain, bleeding, di ...
, where a doctor feels the pelvic area for unusual masses that could be tumors. Severe bladder tumors often shed cells into the urine; these can be detected by urine cytology
Urine cytology is a test that looks for abnormal cells in urine under a microscope. The test commonly checks for infection, inflammatory disease of the urinary tract, cancer, or precancerous conditions. It can be part of a broader urinalysis. If a ...
, where cells are collected from a urine sample, and viewed under a microscope
A microscope () is a laboratory equipment, laboratory instrument used to examine objects that are too small to be seen by the naked eye. Microscopy is the science of investigating small objects and structures using a microscope. Microscopic ...
.[ Cytology can detect around two thirds of high-grade tumors, but detects just 1 in 8 low-grade tumors. Additional urine tests can be used to detect molecules associated with bladder cancer. Some detect the ]bladder tumor antigen
The bladder tumour antigen (BTA) test is used in the detection of bladder cancer
Bladder cancer is the abnormal growth of cells in the bladder. These cells can grow to form a tumor, which eventually spreads, damaging the bladder and other ...
(BTA) protein, or NMP22 NMP22 is a tumor marker for bladder cancer.
NMP22 is the abbreviated form of Nuclear Matrix Protein Number 22.
It reflects the mitotic
Mitosis () is a part of the cell cycle in eukaryotic cells in which replicated chromosomes are separated ...
that tend to be elevated in the urine of those with bladder cancer; some detect the mRNA
In molecular biology, messenger ribonucleic acid (mRNA) is a single-stranded molecule of RNA that corresponds to the genetic sequence of a gene, and is read by a ribosome in the process of Protein biosynthesis, synthesizing a protein.
mRNA is ...
of tumor-associated genes; some use fluorescence microscopy
A fluorescence microscope is an optical microscope that uses fluorescence instead of, or in addition to, scattering, reflection, and attenuation or absorption, to study the properties of organic or inorganic substances. A fluorescence micro ...
to detect cancerous cells, which is more sensitive than regular microscopy.
The upper urinary tract (ureter
The ureters are tubes composed of smooth muscle that transport urine from the kidneys to the urinary bladder. In an adult human, the ureters typically measure 20 to 30 centimeters in length and about 3 to 4 millimeters in diameter. They are lin ...
s and kidney
In humans, the kidneys are two reddish-brown bean-shaped blood-filtering organ (anatomy), organs that are a multilobar, multipapillary form of mammalian kidneys, usually without signs of external lobulation. They are located on the left and rig ...
) is also imaged for tumors that could cause blood in the urine. This is typically done by injecting a dye into the blood that the kidneys will filter into the urinary tract, then imaging by CT scanning
A computed tomography scan (CT scan), formerly called computed axial tomography scan (CAT scan), is a medical imaging technique used to obtain detailed internal images of the body. The personnel that perform CT scans are called radiographers or ...
. Those whose kidneys are not functioning well enough to filter the dye may instead be scanned by MRI
Magnetic resonance imaging (MRI) is a medical imaging technique used in radiology to generate pictures of the anatomy and the physiological processes inside the body. MRI scanners use strong magnetic fields, magnetic field gradients, and rad ...
. Alternatively, the upper urinary tract can be imaged with ultrasound
Ultrasound is sound with frequency, frequencies greater than 20 Hertz, kilohertz. This frequency is the approximate upper audible hearing range, limit of human hearing in healthy young adults. The physical principles of acoustic waves apply ...
.[
]
Classification
Bladder tumors are classified by their appearance under the microscope, and by their cell type of origin. Over 90% of bladder tumors arise from the cells that form the bladder's inner lining, called urothelial cells or transitional cells; the tumor is then classified as urothelial cancer or transitional cell cancer
Transitional cell carcinoma is a type of cancer that arises from the transitional epithelium, a tissue lining the inner surface of these hollow organs. It typically occurs in the urothelium of the urinary system; in that case, it is also called ...
. Around 5% of cases are squamous cell cancer
Squamous-cell carcinoma (SCC), also known as epidermoid carcinoma, comprises a number of different types of cancer that begin in squamous cells. These cells form on the surface of the skin, on the lining of hollow organs in the body, and on the ...
(from a rarer cell in the bladder lining), which are less rare in countries where schistosomiasis
Schistosomiasis, also known as snail fever, bilharzia, and Katayama fever is a neglected tropical helminthiasis, disease caused by parasitism, parasitic Schistosoma, flatworms called schistosomes. It affects both humans and animals. It affects ...
occurs.[ Up to 2% of cases are ]adenocarcinoma
Adenocarcinoma (; plural adenocarcinomas or adenocarcinomata ; AC) is a type of cancerous tumor that can occur in several parts of the body. It is defined as neoplasia of epithelial tissue that has glandular origin, glandular characteristics, or ...
(from mucus
Mucus (, ) is a slippery aqueous secretion produced by, and covering, mucous membranes. It is typically produced from cells found in mucous glands, although it may also originate from mixed glands, which contain both Serous fluid, serous and muc ...
-producing gland cells).[ The remaining cases are ]sarcoma
A sarcoma is a rare type of cancer that arises from cells of mesenchymal origin. Originating from mesenchymal cells means that sarcomas are cancers of connective tissues such as bone, cartilage, muscle, fat, or vascular tissues.
Sarcom ...
s (from the bladder muscle) or small-cell cancer (from neuroendocrine cell
Neuroendocrine cells are cells that receive neuronal input (through neurotransmitters released by nerve cells or neurosecretory cells) and, as a consequence of this input, release messenger molecules (hormones) into the blood. In this way they bri ...
s), both of which are relatively rare.[
The pathologist also ]grades
Grade most commonly refers to:
* Grading in education, a measurement of a student's performance by educational assessment (e.g. A, pass, etc.)
* A designation for students, classes and curricula indicating the number of the year a student has reach ...
the tumor sample based on how distinct the cancerous cells look from healthy cells. Bladder cancer is divided into either low-grade (more similar to healthy cells) or high-grade (less similar).
Staging
A bladder cancer case is assigned a stage
Stage, stages, or staging may refer to:
Arts and media Acting
* Stage (theatre), a space for the performance of theatrical productions
* Theatre, a branch of the performing arts, often referred to as "the stage"
* ''The Stage'', a weekly Brit ...
based on the TNM system. A tumor is assigned three scores based on the extent of the primary tumor (T), its spread to nearby lymph nodes (N), and metastasis to distant sites (M).
The T score represents the extent of the original tumor. Tumors confined to the innermost layer of the bladder are designated Tis (for CIS tumors) or Ta (all others). Otherwise they are assigned a numerical score based on how far they have spread: into the bladder's connective tissue (T1), bladder muscle (T2), surrounding fatty tissue (T3) or extension fully outside the bladder (T4).[ The N score represents spread to nearby lymph nodes: N0 for no spread; N1 for spread to a single nearby lymph node; N2 for spread to several nearby lymph nodes; N3 for spread to more distant lymph nodes outside the pelvis.][ The M score designates spread to distant organs: M0 for a tumor that has not spread; M1 for one that has.][ The TNM scores are combined to determine the cancer case's stage on a scale of 0 to 4. A higher stage means a more extensive cancer with a poorer prognosis.
Around 75% of cases are confined to the bladder at the time of diagnosis (T scores: Tis, Ta, or T1), and are called non-muscle-invasive bladder cancer (NMIBC). Around 18% have tumors that have spread into the bladder muscle (T2, T3, or T4), and are called muscle-invasive bladder cancer (MIBC). Around 3% have tumors that have spread to organs far from the bladder, and are called metastatic bladder cancer. Those with more extensive tumor spread tend to have a poorer prognosis.
]
Treatment
Non-muscle-invasive bladder cancer
NMIBC is primarily treated by surgically removing all tumors by TURBT in the same procedure used to collect biopsy tissue for diagnosis. For those with a relatively low risk of tumors recurring, a single bladder injection of chemotherapy (mitomycin C
Mitomycin C is a mitomycin that is used as a chemotherapy, chemotherapeutic agent by virtue of its antitumour activity.
Medical uses
It is given intravenously to treat upper gastro-intestinal cancers (e.g. esophageal carcinoma), anal cancer ...
, epirubicin
Epirubicin is an anthracycline drug used for chemotherapy. It can be used in combination with other medications to treat breast cancer in patients who have had surgery to remove the tumor. It is marketed by Pfizer under the trade name Ellence in ...
, or gemcitabine
Gemcitabine, sold under the brand name Gemzar, among others, is a chemotherapy medication used to treat cancers. It is used to treat testicular cancer, breast cancer, ovarian cancer, non-small cell lung cancer, pancreatic cancer, and bladder ca ...
) reduces the risk of tumors regrowing by about 40%. Those with higher risk are instead treated with bladder injections of the BCG vaccine
The Bacillus Calmette–Guérin (BCG) vaccine is a vaccine primarily used against tuberculosis (TB). It is named after its inventors Albert Calmette and Camille Guérin. In countries where tuberculosis or leprosy is common, one dose is recom ...
(a live bacterial vaccine, traditionally used for tuberculosis
Tuberculosis (TB), also known colloquially as the "white death", or historically as consumption, is a contagious disease usually caused by ''Mycobacterium tuberculosis'' (MTB) bacteria. Tuberculosis generally affects the lungs, but it can al ...
), administered weekly for six weeks. This nearly halves the rate of tumor recurrence. Recurrence risk is further reduced by a series of "maintenance" BCG injections, given regularly for at least a year. Tumors that do not respond to BCG may be treated with the alternative immune stimulants nadofaragene firadenovec (sold as "Adstiladrin", a gene therapy
Gene therapy is Health technology, medical technology that aims to produce a therapeutic effect through the manipulation of gene expression or through altering the biological properties of living cells.
The first attempt at modifying human DNA ...
that makes bladder cells produce an immunostimulant
Immunostimulants, also known as immunostimulators, are substances (drugs and nutrients) that stimulate the immune system usually in a non-specific manner by inducing activation or increasing activity of any of its components. One notable example i ...
protein), nogapendekin alfa inbakicept ("Anktiva", a combination of immunostimulant proteins), or pembrolizumab
Pembrolizumab, sold under the brand name Keytruda, is a humanized antibody, more specifically a PD-1 inhibitor, used in cancer immunotherapy that treats melanoma, lung cancer, head and neck cancer, Hodgkin lymphoma, stomach cancer, cerv ...
("Keytruda", an immune checkpoint inhibitor).
People whose tumors continue to grow are often treated with surgery to remove the bladder and surrounding organs, called radical 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. The most common condition warranting removal of the urinary bladder is bladder cancer.
Two mai ...
. The bladder, several adjacent lymph node
A lymph node, or lymph gland, is a kidney-shaped organ of the lymphatic system and the adaptive immune system. A large number of lymph nodes are linked throughout the body by the lymphatic vessels. They are major sites of lymphocytes that includ ...
s, the lower ureter
The ureters are tubes composed of smooth muscle that transport urine from the kidneys to the urinary bladder. In an adult human, the ureters typically measure 20 to 30 centimeters in length and about 3 to 4 millimeters in diameter. They are lin ...
s, and nearby internal genital organs – in men the prostate
The prostate is an male accessory gland, accessory gland of the male reproductive system and a muscle-driven mechanical switch between urination and ejaculation. It is found in all male mammals. It differs between species anatomically, chemica ...
and seminal vesicles
The seminal vesicles (also called vesicular glands or seminal glands) are a pair of convoluted tubular accessory glands that lie behind the urinary bladder of male mammals. They secrete fluid that largely composes the semen.
The vesicles are 5 ...
; in women the womb
The uterus (from Latin ''uterus'', : uteri or uteruses) or womb () is the organ in the reproductive system of most female mammals, including humans, that accommodates the embryonic and fetal development of one or more fertilized eggs until bi ...
and part of the vagina
In mammals and other animals, the vagina (: vaginas or vaginae) is the elastic, muscular sex organ, reproductive organ of the female genital tract. In humans, it extends from the vulval vestibule to the cervix (neck of the uterus). The #Vag ...
l wall – are all removed.
Surgeons then construct a new way for urine to leave the body. The most common method is by ileal conduit, where a piece of the ileum
The ileum () is the final section of the small intestine in most higher vertebrates, including mammals, reptiles, and birds. In fish, the divisions of the small intestine are not as clear and the terms posterior intestine or distal intestine may ...
(part of the small intestine) is removed and used to transport urine from the ureters to a new surgical opening (stoma
In botany, a stoma (: stomata, from Greek language, Greek ''στόμα'', "mouth"), also called a stomate (: stomates), is a pore found in the Epidermis (botany), epidermis of leaves, stems, and other organs, that controls the rate of gas exc ...
) in the abdomen. Urine drains passively into an ostomy bag
An ostomy pouching system is a prosthetic medical device that provides a means for the collection of waste from a surgically diverted biological system ( colon, ileum, bladder) and the creation of a stoma. Pouching systems are most commonly asso ...
worn outside the body, which can be emptied regularly by the wearer. Alternatively, one can have a continent urinary diversion
A continent is any of several large geographical regions. Continents are generally identified by convention rather than any strict criteria. A continent could be a single large landmass, a part of a very large landmass, as in the case of As ...
, where the ureters are attached to a piece of ileum that includes the valve between the small and large intestine; this valve naturally closes, allowing urine to be retained in the body rather than in an ostomy bag. The affected person empties the new urine reservoir several times each day by self-catheterization
In medicine, a catheter ( ) is a thin tube made from medical grade materials serving a broad range of functions. Catheters are medical devices that can be inserted in the body to treat diseases or perform a surgical procedure. Catheters are man ...
– passing a narrow tube through the stoma. Some can instead have the piece of ileum attached directly to the urethra, allowing the affected person to urinate through the urethra as they would pre-surgery – although without the original bladder nerves, they will no longer have the urge to urinate when the urine reservoir is full.
Those not well enough or unwilling to undergo radical cystectomy may instead benefit from further bladder injections of chemotherapy – mitomycin C
Mitomycin C is a mitomycin that is used as a chemotherapy, chemotherapeutic agent by virtue of its antitumour activity.
Medical uses
It is given intravenously to treat upper gastro-intestinal cancers (e.g. esophageal carcinoma), anal cancer ...
, gemcitabine
Gemcitabine, sold under the brand name Gemzar, among others, is a chemotherapy medication used to treat cancers. It is used to treat testicular cancer, breast cancer, ovarian cancer, non-small cell lung cancer, pancreatic cancer, and bladder ca ...
, docetaxel
Docetaxel (DTX or DXL), sold under the brand name Taxotere among others, is a chemotherapy medication used to treat a number of types of cancer. This includes breast cancer, head and neck cancer, stomach cancer, prostate cancer and non-small-cel ...
, or valrubicin
Valrubicin (''N''-trifluoroacetyladriamycin-14-valerate, trade name Valstar) 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 ...
– or intravenous injection
Intravenous therapy (abbreviated as IV therapy) is a medical technique that administers fluids, medications and nutrients directly into a person's vein. The intravenous route of administration is commonly used for rehydration or to provide nutr ...
of pembrolizumab
Pembrolizumab, sold under the brand name Keytruda, is a humanized antibody, more specifically a PD-1 inhibitor, used in cancer immunotherapy that treats melanoma, lung cancer, head and neck cancer, Hodgkin lymphoma, stomach cancer, cerv ...
. Around 1 in 5 people with NMIBC will eventually progress to MIBC.
Most people with muscle-invasive bladder cancer are treated with radical cystectomy, which cures around half of those affected. Treating with chemotherapy prior to surgery (called "neoadjuvant therapy
Neoadjuvant therapy is the administration of therapeutic agents before a main treatment. One example is neoadjuvant hormone therapy prior to radical radiotherapy for adenocarcinoma of the prostate. Neoadjuvant therapy aims to reduce the size o ...
") using a cisplatin
Cisplatin is a chemical compound with chemical formula, formula ''cis''-. It is a coordination complex of platinum that is used as a chemotherapy medication used to treat a number of cancers. These include testicular cancer, ovarian cancer, c ...
-containing drug combination (gemcitabine plus cisplatin; or methotrexate
Methotrexate, formerly known as amethopterin, is a chemotherapy agent and immunosuppressive drug, immune-system suppressant. It is used to treat cancer, autoimmune diseases, and ectopic pregnancy, ectopic pregnancies. Types of cancers it is u ...
, vinblastine, doxorubicin
Doxorubicin, sold under the brand name Adriamycin among others, is a chemotherapy medication used to treat cancer. This includes breast cancer, bladder cancer, Kaposi's sarcoma, lymphoma, and acute lymphocytic leukemia. It is often used toge ...
, and cisplatin) improves survival an additional 5 to 10%.
Those with certain types of lower-risk disease may instead receive bladder-sparing therapy. People with just a single tumor at the back of the bladder can undergo partial cystectomy, with the tumor and surrounding area removed, and the bladder repaired. Those with no CIS or urinary blockage may undergo TURBT to remove visible tumors, followed by chemotherapy and radiotherapy
Radiation therapy or radiotherapy (RT, RTx, or XRT) is a treatment using ionizing radiation, generally provided as part of cancer therapy to either kill or control the growth of malignant cells. It is normally delivered by a linear particle ...
, known as "trimodality therapy". Around two thirds of these people are cured. After treatment, surveillance tests – urine and blood tests, and MRI or CT scans – are done every three to six months to look for evidence that tumors may be recurring. Those who have retained their bladder also receive cystoscopies to look for additional bladder tumors. If cancer is found in lymph nodes removed during surgery, or there is high risk of recurrence, radiotherapy may be given after surgery. Recurrent bladder tumors are treated with radical cystectomy. Tumor recurrences elsewhere are treated as metastatic bladder cancer.
Metastatic disease
Stage IV bladder cancer that has reached the pelvic or abdominal wall (T4b), spread to distant lymph nodes (M1a) or other parts of the body (M1b) is difficult to completely remove surgically, the initial treatment usually being chemotherapy.
The 2022 standard of care
In tort law, the standard of care is the only degree of prudence and caution required of an individual who is under a duty of care.
The requirements of the standard are closely dependent on circumstances. Whether the standard of care has been b ...
for metastatic bladder cancer is combination treatment with the chemotherapy drugs cisplatin
Cisplatin is a chemical compound with chemical formula, formula ''cis''-. It is a coordination complex of platinum that is used as a chemotherapy medication used to treat a number of cancers. These include testicular cancer, ovarian cancer, c ...
and gemcitabine
Gemcitabine, sold under the brand name Gemzar, among others, is a chemotherapy medication used to treat cancers. It is used to treat testicular cancer, breast cancer, ovarian cancer, non-small cell lung cancer, pancreatic cancer, and bladder ca ...
. The average person on this combination survives around a year, though 15% experience remission, with survival over five years. Around half of those with metastatic bladder cancer are in too poor health to receive cisplatin. They instead receive the related drug carboplatin
Carboplatin, sold under the brand name Paraplatin among others, is a chemotherapy medication used to treat a number of forms of cancer. This includes ovarian cancer, lung cancer, head and neck cancer, brain cancer, and neuroblastoma. It is a ...
along with gemcitabine; the average person on this regimen survives around 9 months. Those whose disease responds to chemotherapy benefit from switching to immune checkpoint inhibitors pembrolizumab
Pembrolizumab, sold under the brand name Keytruda, is a humanized antibody, more specifically a PD-1 inhibitor, used in cancer immunotherapy that treats melanoma, lung cancer, head and neck cancer, Hodgkin lymphoma, stomach cancer, cerv ...
or atezolizumab
Atezolizumab, sold under the brand name Tecentriq among others, is a monoclonal antibody medication used to treat urothelial carcinoma, non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), hepatocellular carcinoma and alveolar so ...
("Tecentriq") for long-term maintenance therapy
Maintenance therapy is a medical therapy that is designed to help a primary treatment succeed. For example, maintenance chemotherapy may be given to people who have a cancer in remission in an attempt to prevent a relapse. This form of treatment ...
. Immune checkpoint inhibitors are also commonly given to those whose tumors do not respond to chemotherapy, as well as those in too poor health to receive chemotherapy.
Alternate treatment options might include:
* the immunotherapy drug pembrolizumab (Keytruda) combined with the antibody-drug conjugate (ADC) enfortumab vedotin (Padcev). This combination has also been recommended as a first-line therapy in place of chemotherapy.
* the immunotherapy drug nivolumab
Nivolumab, sold under the brand name Opdivo, is an anti-cancer medication in the class of immune checkpoint inhibitors. It selectively binds and blocks the programmed death-1 (PD-1) receptor on T cells, thereby facilitating their activation ...
(Opdivo) in conjunction with chemotherapy
* chemotherapy, followed by the immunotherapy drug avelumab (Bavencio)
Those whose tumors continue to grow after platinum chemotherapy and immune checkpoint inhibitors can receive the ADC enfortumab vedotin ("Padcev", targets tumor cells with the protein nectin-4). Those with genetic alterations that activate the proteins FGFR2 or FGFR3 (around 20% of those with metastatic bladder cancer) can also benefit from the FGFR inhibitor erdafitinib
Erdafitinib, sold under the brand name Balversa, is an anti-cancer medication. It is a small molecule inhibitor of fibroblast growth factor receptor (FGFR) used for the treatment of cancer. FGFRs are a subset of tyrosine kinases which are unr ...
("Balversa").
Bladder cancer that continues growing can be treated with second-line chemotherapies. Vinflunine is used in Europe, while paclitaxel
Paclitaxel, sold under the brand name Taxol among others, is a chemotherapy medication used to treat ovarian cancer, esophageal cancer, breast cancer, lung cancer, Kaposi's sarcoma, cervical cancer, and pancreatic cancer. It is administered b ...
, docetaxel
Docetaxel (DTX or DXL), sold under the brand name Taxotere among others, is a chemotherapy medication used to treat a number of types of cancer. This includes breast cancer, head and neck cancer, stomach cancer, prostate cancer and non-small-cel ...
, and pemetrexed
Pemetrexed, sold under the brand name Alimta among others, is a chemotherapy medication for the treatment of pleural mesothelioma and non-small cell lung cancer (NSCLC).
It is available as a generic medication.
Medical use
In February 2004, th ...
are used in the United States; only a minority of those treated improve on these therapies.
If medicines are no longer controlling the cancer, other treatments may still be helpful, e.g., palliative care
Palliative care (from Latin root "to cloak") is an interdisciplinary medical care-giving approach aimed at optimizing quality of life and mitigating or reducing suffering among people with serious, complex, and often terminal illnesses. Man ...
that focuses on preventing or relieving problems the cancer may cause.
Because metastatic bladder cancers are rarely cured by current treatment methods, many experts suggest considering clinical trial
Clinical trials are prospective biomedical or behavioral research studies on human subject research, human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel v ...
s evaluating alternative treatments.
Treatment adverse effects
Radical cystectomy has both immediate and lifelong side effects. It is common for those recovering from surgery to experience gastrointestinal problems (29% of those who underwent radical cystectomy), infections (25%), and other issues with the surgical wound (15%). Around 25% of those who undergo the surgery end up readmitted to the hospital within 30 days; up to 2% die within 30 days of the surgery.
Rerouting the ureters, urinary diversions, can cause permanent metabolic issues. The piece of ileum used to reroute urine flow can absorb more ion
An ion () is an atom or molecule with a net electrical charge. The charge of an electron is considered to be negative by convention and this charge is equal and opposite to the charge of a proton, which is considered to be positive by convent ...
s from the urine than the original bladder would, resulting in metabolic acidosis
Metabolic acidosis is a serious electrolyte disorder characterized by an imbalance in the body's acid-base balance. Metabolic acidosis has three main root causes: increased acid production, loss of bicarbonate, and a reduced ability of the kidn ...
(blood becoming too acidic), which can be treated with sodium bicarbonate
Sodium bicarbonate ( IUPAC name: sodium hydrogencarbonate), commonly known as baking soda or bicarbonate of soda (or simply “bicarb” especially in the UK) is a chemical compound with the formula NaHCO3. It is a salt composed of a sodium cat ...
.
Shortening the small intestine can result in reduced vitamin B12
Vitamin B12, also known as cobalamin, is a water-soluble vitamin involved in metabolism. One of eight B vitamins, it serves as a vital cofactor (biochemistry), cofactor in DNA synthesis and both fatty acid metabolism, fatty acid and amino a ...
absorption, which can be treated with oral vitamin B12 supplementation. Issues with the new urine system can cause urinary retention, which can damage the ureters and kidneys and increase one's risk of urinary tract infection.
Chemotherapy common side effects include; hair loss, mouth sores, loss of appetite, diarrhea, nausea and vomiting, premature menopause, infertility, and damage to the blood-forming cells within bone marrow. Most acute side effects are temporary, dissipating when treatment ceases, but some can be long-lasting or permanent. Long-term chemotherapy side effects include changes in the menstrual cycle, neuropathy, and nephrotoxicity
Nephrotoxicity is toxicity in the kidneys. It is a poisonous effect of some substances, both toxic chemicals and medications, on kidney function. There are various forms, and some drugs may affect kidney function in more than one way. Nephrotoxin ...
.
Checkpoint inhibitor (immunotherapy) side effects commonly include injection site pain, soreness, itchiness or rash. Additional flu-like symptoms may occur like fever, weakness, dizziness, nausea or vomiting, headache, fatigue, or blood pressure changes. More serious side effects might include heart palpitations, diarrhea, infection and organ inflammation. Some people might have allergic reactions
Allergies, also known as allergic diseases, are various conditions caused by hypersensitivity of the immune system to typically harmless substances in the environment. These diseases include hay fever, food allergies, atopic dermatitis, alle ...
with wheezing or breathing problems. Autoimmune reactions are possible because checkpoint inhibitors function by altering or removing immune system safeguards which can cause serious or even life-threatening problems.
Antibody-drug conjugate side effects frequently include diarrhea and liver problems. Other side effects might include issues with blood clotting and wound healing, high blood pressure, fatigue, mouth sores, nail changes, loss of hair color, skin rash, or dry skin. Very rarely, a hole might form through the wall of the esophagus, stomach, small intestine, large bowel, rectum, or gallbladder.
Radiotherapy acute side effects involve the gastrointestinal system, e.g., diarrhea and constipation; the urinary tract; and may cause cervicitis
Cervicitis is inflammation of the uterine cervix. Cervicitis in women has many features in common with urethritis in men and many cases are caused by sexually transmitted infections. Non-infectious causes of cervicitis can include intrauterine ...
. Common late effects include: premature ovarian failure
Primary ovarian insufficiency (POI), also called premature ovarian insufficiency and premature ovarian failure, is the partial or total loss of reproductive and hormonal function of the ovaries before age 40 because of follicular ( egg produc ...
; telangiectasias
Telangiectasias (), also known as spider veins, are small dilated blood vessels that can occur near the surface of the skin or mucous membranes, measuring between 0.5 and 1 millimeter in diameter. These dilated blood vessels can develop anywhere ...
, and subsequent hemorrhage; and progressive myelopathy. Pelvic radiotherapy late effects (with occurrence rates) include osteonecrosis
Avascular necrosis (AVN), also called osteonecrosis or bone infarction, is death of bone tissue due to interruption of the blood supply. Early on, there may be no symptoms. Gradually joint pain may develop, which may limit the person's abili ...
(8-20%), vaginal stenosis (>2.5%) and chronic pelvic radiation disease
:''(Redirected from "Pelvic Radiation Disease")''
Radiation enteropathy is a syndrome that may develop following abdominal or pelvic radiation therapy for cancer. Many affected people are cancer survivors who had treatment for cervical cancer or ...
(1-10%), e.g., lumbosacral plexopathy. Radiation also induces secondary malignancies such as leukemia
Leukemia ( also spelled leukaemia; pronounced ) is a group of blood cancers that usually begin in the bone marrow and produce high numbers of abnormal blood cells. These blood cells are not fully developed and are called ''blasts'' or '' ...
, lymphoma
Lymphoma is a group of blood and lymph tumors that develop from lymphocytes (a type of white blood cell). The name typically refers to just the cancerous versions rather than all such tumours. Signs and symptoms may include enlarged lymph node ...
, bone and soft-tissue sarcoma
A soft-tissue sarcoma (STS) is a malignant tumor, a type of cancer, that develops in soft tissue. A soft-tissue sarcoma is often a painless mass that grows slowly over months or years. They may be superficial or deep-seated. Any such unexplained ...
with occurrence rates between 0.2-1.0% per year for each. See also: Radiation therapy#Side effects.
Causes
Bladder cancer is caused by changes to the DNA
Deoxyribonucleic acid (; DNA) is a polymer composed of two polynucleotide chains that coil around each other to form a double helix. The polymer carries genetic instructions for the development, functioning, growth and reproduction of al ...
of bladder cells that result in those cells growing uncontrollably.[ These changes can be random, or can be induced by exposure to toxic substances such as those from consuming tobacco. Genetic damage accumulates over many years, eventually disrupting the normal functioning of bladder cells and causing them to grow uncontrollably into a lump of cells called a tumor.] Cancer cells accumulate further DNA changes as they multiply, which can allow the tumor to evade the immune system
The immune system is a network of biological systems that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to bacteria, as well as Tumor immunology, cancer cells, Parasitic worm, parasitic ...
, resist regular cell death pathway
Programmed cell death (PCD) sometimes referred to as cell, or cellular suicide is the death of a cell (biology), cell as a result of events inside of a cell, such as apoptosis or autophagy. PCD is carried out in a biological process, which usual ...
s, and eventually spread to distant body sites. The new tumors that form in various organs damage those organs, eventually causing the death of the affected person.
Smoking
Tobacco smoking
Tobacco smoking is the practice of burning tobacco and ingesting the resulting smoke. The smoke may be inhaled, as is done with cigarettes, or released from the mouth, as is generally done with pipes and cigars. The practice is believed to hav ...
is the main contributor to bladder cancer risk; around half of bladder cancer cases are estimated to be caused by smoking. Tobacco smoke contains carcinogen
A carcinogen () is any agent that promotes the development of cancer. Carcinogens can include synthetic chemicals, naturally occurring substances, physical agents such as ionizing and non-ionizing radiation, and biologic agents such as viruse ...
ic molecules that enter the blood and are filtered by the kidneys into the urine. There they can cause damage to the DNA of bladder cells, eventually leading to cancer. Bladder cancer risk rises both with number of cigarettes smoked per day, and with duration of smoking habit. Those who smoke also tend to have an increased risk of treatment failure, metastasis, and death. The risk of developing bladder cancer decreases in those who quit smoking, falling by 30% after five years of smoking abstention. However, the risk will remain higher than those who have never smoked before. Because development of bladder cancer takes many years, it is not yet known if use of electronic cigarette
An electronic cigarette (e-cigarette), or vape, is a device that simulates smoking. It consists of an atomizer, a power source such as a battery, and a container such as a cartridge or tank. Instead of smoke, the user inhales vapor. As such ...
s carries the same risk as smoking tobacco; however, those who use electronic cigarettes have higher levels of some urinary carcinogens than those who do not.
Occupational exposure
Up to 10% of bladder cancer cases are caused by workplace exposure to toxic chemicals. Exposure to certain aromatic amine
In organic chemistry, an aromatic amine is an organic compound
Some chemical authorities define an organic compound as a chemical compound that contains a carbon–hydrogen or carbon–carbon bond; others consider an organic compound to be a ...
s, namely benzidine
Benzidine (trivial name), also called 1,1'-biphenyl-4,4'-diamine (systematic name), is an organic compound with the chemical formula, formula (C6H4NH2)2. It is an aromatic amine. It is a component of a test for cyanide. Related derivatives are ...
, beta-naphthylamine, and ortho-toluidine used in the metalworking and dye industries, can increase the risk of bladder cancer in metalworkers, dye producers, painters, printers, hairdressers, and textiles workers. The International Agency for Research on Cancer
The International Agency for Research on Cancer (IARC; ) is an intergovernmental agency forming part of the World Health Organization of the United Nations.
Its role is to conduct and coordinate research into the causes of cancer. It also cance ...
further classifies rubber processing, aluminum production, and firefighting as occupations that increase one's risk of developing bladder cancer. Exposure to arsenic
Arsenic is a chemical element; it has Symbol (chemistry), symbol As and atomic number 33. It is a metalloid and one of the pnictogens, and therefore shares many properties with its group 15 neighbors phosphorus and antimony. Arsenic is not ...
– either through workplace exposure or through drinking water in places where arsenic naturally contaminates groundwater – is also commonly linked to bladder cancer risk.
Medical conditions
Chronic bladder infections can increase one's risk of developing bladder cancer. Most prominent is schistosomiasis
Schistosomiasis, also known as snail fever, bilharzia, and Katayama fever is a neglected tropical helminthiasis, disease caused by parasitism, parasitic Schistosoma, flatworms called schistosomes. It affects both humans and animals. It affects ...
, in which the eggs of the flatworm ''Schistosoma haematobium
''Schistosoma haematobium'' (urinary blood fluke) is a species of digenetic trematode, belonging to a group (genus) of blood flukes (''Schistosoma''). It is found in Africa and the Middle East. It is the major agent of schistosomiasis, the mos ...
'' can become lodged in the bladder wall, causing chronic bladder inflammation and repeated bladder infections. In places with endemic
Endemism is the state of a species being found only in a single defined geographic location, such as an island, state, nation, country or other defined zone; organisms that are indigenous to a place are not endemic to it if they are also foun ...
schistosomiasis, up to 16% of bladder cancer cases are caused by prior Schistosoma infection. Worms can be cleared by treatment with praziquantel
Praziquantel, sold under the brandname Biltricide among others, is a medication used to treat a number of types of parasitic worm infections in mammals, birds, amphibians, reptiles, and fish. In humans specifically, it is used to treat schist ...
, which reduces bladder cancer cases in schistosomiasis endemic areas. Similarly, those with long-term indwelling catheters are at risk for repeated urinary tract infections, and have increased risk of developing bladder cancer.
Some medical treatments are also known to increase bladder cancer risk. As many as 16% of those treated with the chemotherapeutic cyclophosphamide
Cyclophosphamide (CP), also known as cytophosphane among other names, is a medication used as chemotherapy and to suppress the immune system. As chemotherapy it is used to treat lymphoma, multiple myeloma, leukemia, ovarian cancer, breast cancer ...
go on to develop bladder cancer within 15 years of their treatment. Similarly, those treated with pelvic radiation (typically for prostate or cervical cancer) are at increased risk of developing bladder cancer five to 15 years after treatment. Long-term use of the medication pioglitazone
Pioglitazone, sold under the brand name Actos among others, is an anti-diabetic medication used to treat type 2 diabetes. It may be used with metformin, a sulfonylurea, or insulin. Use is recommended together with exercise and diet. It is not ...
for type 2 diabetes
Type 2 diabetes (T2D), formerly known as adult-onset diabetes, is a form of diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. Common symptoms include increased thirst, frequent ...
may increase bladder cancer risk.
Genetics
Bladder cancer does not typically run in families. Only 4% of those diagnosed with bladder cancer have a parent or sibling with the disease, potentially inheriting a gene syndrome associated with bladder cancer, for example:
* Mutations of the RB1 gene, while associated with 95% of Retinoblastoma
Retinoblastoma (Rb) is a rare form of cancer that rapidly develops from the immature cells of a retina, the light-detecting tissue of the eye. It is the most common primary malignant intraocular cancer in children, and 80% of retinoblastoma cas ...
cases, are also linked with bladder cancer.
* Cowden disease is caused by mutations in the PTEN gene; see Cowden syndrome#Genetics. People with this syndrome have increased risk of developing several cancers, including bladder cancer.
* Lynch syndrome
Hereditary nonpolyposis colorectal cancer (HNPCC) is a hereditary predisposition to colon cancer.
HNPCC includes (and was once synonymous with) Lynch syndrome, an autosomal dominant genetic condition that is associated with a high risk of colon ...
is caused by mutations in DNA mismatch repair
DNA mismatch repair (MMR) is a system for recognizing and repairing erroneous insertion, deletion, and mis-incorporation of nucleobase, bases that can arise during DNA replication and Genetic recombination, recombination, as well as DNA repair, ...
genes MLH1
DNA mismatch repair protein Mlh1 or MutL protein homolog 1 is a protein that in humans is encoded by the ''MLH1'' gene located on chromosome 3. The gene is commonly associated with hereditary nonpolyposis colorectal cancer. Orthologs of human ...
, MSH2
DNA mismatch repair protein Msh2 also known as MutS homolog 2 or MSH2 is a protein that in humans is encoded by the ''MSH2'' gene, which is located on chromosome 2. MSH2 is a tumor suppressor gene and more specifically a caretaker gene that codes ...
, MSH6
MSH6 or mutS homolog 6 is a gene that codes for DNA mismatch repair protein Msh6 in the budding yeast ''Saccharomyces cerevisiae''. It is the homologue of the human "G/T binding protein," (GTBP) also called p160 or hMSH6 (human MSH6). The MSH6 pr ...
or PMS2
Mismatch repair endonuclease PMS2 (postmeiotic segregation increased 2) is an enzyme that in humans is encoded by the ''PMS2'' gene.
Function
This gene is one of the PMS2 gene family members which are found in clusters on chromosome 7. Human ...
; see main article Hereditary nonpolyposis colorectal cancer
Hereditary nonpolyposis colorectal cancer (HNPCC) is a hereditary predisposition to colon cancer.
HNPCC includes (and was once synonymous with) Lynch syndrome, an autosomal dominant genetic condition that is associated with a high risk of colon ...
(HNPCC). People with this syndrome have increased risk of developing several cancers, including bladder and urinary tract cancers.
Large population studies have identified additional gene variant
Genetic variation is the difference in DNA among individuals or the differences between populations among the same species. The multiple sources of genetic variation include mutation and genetic recombination. Mutations are the ultimate sources ...
s that each slightly increase bladder cancer risk. Most of these are variants in genes involved in metabolism of carcinogens (NAT2
N-acetyltransferase 2 (arylamine N-acetyltransferase), also known as NAT2, is an enzyme which in humans is encoded by the ''NAT2'' gene.
Function
This gene encodes a type of N-acetyltransferase. The NAT2 isozyme functions to both activate and ...
, GSTM1, and UGT1A6
UDP-glucuronosyltransferase 1-6 is an enzyme that in humans is encoded by the ''UGT1A6'' gene.
Function
UDP-glucuronosyltransferase 1-6 is a UDP-glucuronosyltransferase, an enzyme of the glucuronidation pathway that transforms small lipophil ...
), controlling cell growth ( TP63, CCNE1
G1/S-specific cyclin-E1 is a protein that in humans is encoded by the ''CCNE1'' gene.
Function
The protein encoded by this gene belongs to the highly conserved cyclin family, whose members are characterized by a dramatic periodicity in prot ...
, MYC
''Myc'' is a family of regulator genes and proto-oncogenes that code for transcription factors. The ''Myc'' family consists of three related human genes: ''c-myc'' ( MYC), ''l-myc'' ( MYCL), and ''n-myc'' ( MYCN). ''c-myc'' (also sometimes r ...
, and FGFR3
Fibroblast growth factor receptor 3 (FGFR-3) is a protein that in humans is encoded by the ''FGFR3'' gene. FGFR3 has also been designated as CD333 (cluster of differentiation 333). The gene, which is located on chromosome 4, location p16.3, is e ...
), or repairing DNA damage
DNA repair is a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its genome. A weakened capacity for DNA repair is a risk factor for the development of cancer. DNA is constantly modified ...
( NBN, XRCC1 and 3, and ERCC2, 4, and 5).
Diet and lifestyle
Several studies have examined the impact of lifestyle factors on the risk of developing bladder cancer. A 2018 summary of evidence from the World Cancer Research Fund
World Cancer Research Fund (WCRF UK) is a cancer prevention charity in the United Kingdom that is part of the World Cancer Research Fund International network.
The World Cancer Research Fund funds scientific research into how diet, physical acti ...
and American Institute for Cancer Research
The American Institute for Cancer Research (AICR) is a large American cancer research organization associated with the World Cancer Research Fund umbrella organization.
As of 2024, the charity has a four-star rating from Charity Navigator
C ...
concluded that there is "limited, suggestive evidence" that consumption of tea, and a diet high in fruits and vegetables reduce a person's risk of developing bladder cancer. They also considered available data on exercise, body fat, and consumption of dairy, red meat, fish, grains, legumes
Legumes are plants in the pea family Fabaceae (or Leguminosae), or the fruit or seeds of such plants. When used as a dry grain for human consumption, the seeds are also called pulses. Legumes are grown agriculturally, primarily for human consu ...
, eggs, fats, soft drinks, alcohol, juices, caffeine, sweeteners, and various vitamins and minerals; for each they found insufficient data to link the lifestyle factor to bladder cancer risk. Other studies have indicated a slight increased risk of developing bladder cancer in those who are overweight or obese
Obesity is a medical condition, considered by multiple organizations to be a disease, in which excess body fat has accumulated to such an extent that it can potentially have negative effects on health. People are classified as obese when ...
, as well as a slight decrease in risk for those who undertake high levels of physical activity.
Pathophysiology
Bladder tumors typically arise from the urothelium, the cell layer that lines the urine-storing part of the bladder. Parts of the urothelium can accumulate DNA mutations over years, making these areas more likely to give rise to tumors. This effect, called field cancerization
Field cancerization or field effect (also termed field change, field change cancerization, field carcinogenesis, cancer field effect or premalignant field defect) is a biological process in which large areas of cells at a tissue surface or withi ...
, can allow several tumors to arise in the same area, or tumors to re-emerge from a given area after a first tumor was removed. Additionally, a cell that becomes cancerous can grow to give rise to several tumors – nearby and recurrent tumors are often monoclonal (descended from the same cancerous cell).
Despite arising from the same tissue, NMIBC and MIBC develop along distinct pathways and bear distinct genetic mutations. Most NMIBC tumors start as low-grade papillary (finger-like, projecting into the bladder) tumors. Mutations in cell growth pathways are common. Most common are mutations that activate FGFR3
Fibroblast growth factor receptor 3 (FGFR-3) is a protein that in humans is encoded by the ''FGFR3'' gene. FGFR3 has also been designated as CD333 (cluster of differentiation 333). The gene, which is located on chromosome 4, location p16.3, is e ...
(present in up to 80% of NMIBC tumors). Mutations activating the growth pathway PI3K/AKT/mTOR pathway
The PI3K/AKT/mTOR pathway is an intracellular signaling pathway important in regulating the cell cycle. Therefore, it is directly related to cellular quiescence, proliferation, cancer, and longevity. PI3K activation phosphorylates and activates ...
are also common, including mutations in PIK3CA (in around 30% of tumors) and ERBB2
Receptor tyrosine-protein kinase erbB-2 is a protein that normally resides in the membranes of cells and is encoded by the ''ERBB2'' gene. ERBB is abbreviated from erythroblastic oncogene B, a gene originally isolated from the avian genome. The ...
/ERBB3
Receptor tyrosine-protein kinase erbB-3, also known as HER3 (human epidermal growth factor receptor 3), is a membrane bound protein that in humans is encoded by the ''ERBB3'' gene.
ErbB3 is a member of the EGFR family, epidermal growth factor re ...
(up to 15% of tumors), and loss of TSC1
Tuberous sclerosis 1 (TSC1), also known as hamartin, is a protein that in humans is encoded by the ''TSC1'' gene.
Function
TSC1 functions as a co-chaperone which inhibits the ATPase activity of the chaperone Hsp90 (heat shock protein-90) and d ...
(50% of tumors). Major regulators of chromatin
Chromatin is a complex of DNA and protein found in eukaryote, eukaryotic cells. The primary function is to package long DNA molecules into more compact, denser structures. This prevents the strands from becoming tangled and also plays important r ...
(influences the expression of different genes) are inactivated in over 65% of NMIBC tumors.
MIBC often starts with low-lying, flat, high-grade tumors, that quickly spread beyond the bladder. These tumors have more genetic mutations and chromosomal abnormalities overall, with mutations more frequent than in any cancer but lung cancer
Lung cancer, also known as lung carcinoma, is a malignant tumor that begins in the lung. Lung cancer is caused by genetic damage to the DNA of cells in the airways, often caused by cigarette smoking or inhaling damaging chemicals. Damaged ...
and melanoma
Melanoma is the most dangerous type of skin cancer; it develops from the melanin-producing cells known as melanocytes. It typically occurs in the skin, but may rarely occur in the mouth, intestines, or eye (uveal melanoma). In very rare case ...
. Mutations that inactivate the tumor suppressor
A tumor suppressor gene (TSG), or anti-oncogene, is a gene that regulates a cell (biology), cell during cell division and replication. If the cell grows uncontrollably, it will result in cancer. When a tumor suppressor gene is mutated, it results ...
genes TP53
p53, also known as tumor protein p53, cellular tumor antigen p53 (UniProt name), or transformation-related protein 53 (TRP53) is a regulatory transcription factor protein that is often mutated in human cancers. The p53 proteins (originally thou ...
and RB are common, as are mutations in CDH1 (involved in metastasis) and VEGFR2
Kinase insert domain receptor (KDR, a type IV receptor tyrosine kinase) also known as vascular endothelial growth factor receptor 2 (VEGFR-2) is a VEGF receptor. ''KDR'' is the human gene encoding it. KDR has also been designated as CD309 (cluster ...
(involved in cell growth and metastasis).
Some genetic abnormalities are common to NMIBC and MIBC tumors. Around half of each have lost all or part of chromosome 9
Chromosome 9 is one of the 23 pairs of chromosomes in humans. Humans normally have two copies of this chromosome, as they normally do with all chromosomes. Chromosome 9 spans about 138 million base pairs of nucleic acids (the building blocks of DN ...
, which contains several regulators of tumor suppressor
A tumor suppressor gene (TSG), or anti-oncogene, is a gene that regulates a cell (biology), cell during cell division and replication. If the cell grows uncontrollably, it will result in cancer. When a tumor suppressor gene is mutated, it results ...
genes. Up to 80% of tumors have mutations in the gene TERT Tert may refer to:
* ''tert''-, a chemical descriptor prefix used to designate tertiary atoms in molecules
* Telomerase reverse transcriptase
Telomerase reverse transcriptase (abbreviated to TERT, or hTERT in humans) is a catalytic subunit of t ...
, which extends cells' telomere
A telomere (; ) is a region of repetitive nucleotide sequences associated with specialized proteins at the ends of linear chromosomes (see #Sequences, Sequences). Telomeres are a widespread genetic feature most commonly found in eukaryotes. In ...
s to allow for extended replication.
Prognosis
Bladder cancer prognosis varies based on how widespread the cancer is at the time of diagnosis. For those with tumors confined to the innermost layer of the bladder (stage 0 disease), 96% are still alive five years from diagnosis. Those whose tumors have spread to nearby lymph nodes (stage 3 disease) have worse prognoses; 36% survive at least five years from diagnosis. Those with metastatic bladder cancer (stage 4 disease) have the most severe prognosis, with 5% alive five years from diagnosis.
Epidemiology
Around 500,000 people are diagnosed with bladder cancer each year, and 200,000 die of the disease. This makes bladder cancer the tenth most commonly diagnosed cancer, and the thirteenth cause of cancer deaths. Bladder cancer is most common in wealthier regions of the world, where exposure to certain carcinogens is highest. It is also common in places where schistosome
''Schistosoma'' is a genus of trematodes, commonly known as blood flukes. They are parasitic flatworms responsible for a highly significant group of infections in humans termed ''schistosomiasis'', which is considered by the World Health Organ ...
infection is common, such as North Africa.
Bladder cancer is much more common in men than women; around 1.1% of men and 0.27% of women develop bladder cancer. This makes bladder cancer the sixth most common cancer in men, and the seventeenth in women. When women are diagnosed with bladder cancer, they tend to have more advanced disease and consequently a poorer prognosis. This difference in outcomes is attributed to numerous factors such as difference in carcinogen exposure, genetics
Genetics is the study of genes, genetic variation, and heredity in organisms.Hartl D, Jones E (2005) It is an important branch in biology because heredity is vital to organisms' evolution. Gregor Mendel, a Moravian Augustinians, Augustinian ...
, social factors and quality of care.
As with most cancers, bladder cancer is more common in older people; the average person with bladder cancer is diagnosed at age 73. 80% of those diagnosed with bladder cancer are 65 or older; 20% are 85 or older.
Veterinary medicine
Bladder cancer is relatively rare in domestic dogs and cats. In dogs, around 1% of diagnosed cancers are bladder cancer. Shetland sheepdog
The Shetland Sheepdog, also known as the Sheltie, is a breed of herding dog that originated in the Shetland Islands of Scotland. It was formally recognized by the Kennel Club in 1909. It was originally called the ''Shetland Collie'', but this c ...
s, beagle
The Beagle is a small breed of scent hound, similar in appearance to the much larger foxhound. The beagle was developed primarily for hunting rabbit or hare, known as beagling. Possessing a great sense of smell and superior tracking inst ...
s, and various terrier
Terrier () is a Dog type, type of dog originally bred to hunt vermin. A terrier is a dog of any one of many Dog breed, breeds or landraces of the terrier Dog type, type, which are typically small, wiry, Gameness, game, and fearless. There are fi ...
s are at increased risk relative to other breeds. Signs of a bladder tumor – blood in the urine, frequent urination, or trouble urinating – are common to other canine urinary conditions, and so diagnosis is often delayed. Urine tests can aid in diagnosis; they test for the protein bladder tumor antigen
The bladder tumour antigen (BTA) test is used in the detection of bladder cancer
Bladder cancer is the abnormal growth of cells in the bladder. These cells can grow to form a tumor, which eventually spreads, damaging the bladder and other ...
(high in bladder tumors) or mutations in the BRAF gene (present in around 80% of dogs with bladder or prostate cancer). Dogs with confirmed cancer are treated with COX-2 inhibitor
Cyclooxygenase-2 inhibitors (COX-2 inhibitors), also known as coxibs, are a type of nonsteroidal anti-inflammatory drug (NSAID) that directly target cyclooxygenase-2 (COX-2), an enzyme responsible for inflammation and pain. Targeting selectivity ...
drugs, such as piroxicam
Piroxicam is a nonsteroidal anti-inflammatory drug (NSAID) of the oxicam class used to relieve the symptoms of painful inflammatory conditions like arthritis. Piroxicam works by preventing the production of endogenous prostaglandins which are inv ...
, deracoxib, and meloxicam
Meloxicam, sold under the brand name Mobic among others, is a nonsteroidal anti-inflammatory drug (NSAID) used to treat pain and inflammation in rheumatic diseases and osteoarthritis. It is taken by mouth or given by injection into a vein. ...
. These drugs halt disease progression in around 50% of dogs, shrink tumors in around 12%, and eliminate tumors in around 6%. COX-2 inhibitors are often combined with chemotherapy drugs, most commonly mitoxantrone
Mitoxantrone (INN, BAN, USAN; also known as Mitozantrone in Australia; trade name Novantrone) is an anthracenedione antineoplastic agent.
Uses
Mitoxantrone is used to treat certain types of cancer, mostly acute myeloid leukemia. It improves th ...
, vinblastine
Vinblastine, sold under the brand name Velban among others, is a chemotherapy medication, typically used with other medications, to treat a number of types of cancer. This includes Hodgkin's lymphoma, non-small-cell lung cancer, bladder canc ...
, or chlorambucil. Bladder cancer is much less common in cats than in dogs; treatment is similar to that of canine bladder cancer, with chemotherapy and COX-2 inhibitors commonly used.
Charities and funding
Several charities provide support for individuals affected by bladder cancer and fund research into improved treatments. Organisations such as Cancer Research UK
Cancer Research UK (CRUK) is the world's largest independent cancer research organisation. It is registered as a charity in the United Kingdom and Isle of Man, and was formed on 4 February 2002 by the merger of The Cancer Research Campaign and t ...
(United Kingdom), Fight Bladder Cancer
Fight Bladder Cancer is the only patient-led bladder cancer charity in the UK. The charity is dedicated to supporting people affected by bladder cancer, raising awareness, and funding research to improve diagnosis and treatment. It provides sup ...
(United Kingdom), Bladder Cancer Advocacy Network
The bladder () is a hollow organ in humans and other vertebrates that stores urine from the Kidney (vertebrates), kidneys. In placental mammals, urine enters the bladder via the ureters and exits via the urethra during urination. In humans, the ...
(United States), and The World Bladder Cancer Patient Coalition (international), offer patient support, educational resources, and advocacy initiatives. These organisations contribute to research funding, early diagnosis campaigns, and patient support services, aiming to improve outcomes for those diagnosed with bladder cancer. Independent studies and health reports have recognised their role in advancing bladder cancer awareness and care.
References
Works cited
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External links
{{DEFAULTSORT:Bladder Cancer
Health effects of tobacco
Types of cancer