View source for Bladder cancer

{{short description|Urinary system cancer that begins in the urinary bladder}}
{{Use dmy dates|date=September 2020}}
{{cs1 config |name-list-style=vanc |display-authors=6}}
{{Infobox medical condition (new)
| name            = Bladder cancer
| image           = TransCellCaMark.png
| caption         = Transitional cell carcinoma of the bladder. The white in the bladder is contrast.
| field           = [[Oncology]], [[urology]]
| symptoms        = [[hematuria|Blood in the urine]]
| complications   =
| onset           = Age 65 or older
| duration        =
| types           = Non-muscle-invasive bladder cancer (NMIBC), muscle-invasive bladder cancer (MIBC), metastatic bladder cancer
| causes          =
| risks           = [[Tobacco smoking]], exposure to certain toxic chemicals, [[schistosomiasis]] infection
| diagnosis       = [[Cystoscopy]] with [[tissue biopsy]]
| differential    =
| prevention      =
| treatment       = Transurethral resection (TURBT), [[chemotherapy]], [[BCG vaccine]], [[immunotherapy]], [[radical cystectomy]], [[targeted therapy|molecular-targeted therapies]]
| prognosis       = [[Five-year survival rates]] range from 5% to 96% depending on the stage
| frequency       = Around 500,000 each year
| deaths          = Around 200,000 each year
}}

'''Bladder cancer''' is the [[neoplasm|abnormal growth of cells]] in the [[bladder]]. These cells can grow to form a [[tumor]], which eventually spreads, damaging the bladder and other organs. Most people with bladder cancer are diagnosed after noticing [[hematuria|blood in their urine]]. Those suspected of having bladder cancer typically have their bladder inspected by a thin medical camera, a procedure called [[cystoscopy]]. 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 [[cancer staging|stage]] 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]] 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]]). 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 inhibitor]]s, 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]] 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]] also increases the risk.

==Signs and symptoms==
[[File:Blausen 0082 BladderCancer.png|thumb|upright=1.3|Location of bladder cancer]]
The most common symptom of bladder cancer is visible [[blood in the urine]] (haematuria) despite painless urination. This affects around 75% of people eventually diagnosed with the disease.{{sfn|Dyrskjøt|Hansel|Efstathiou|Knowles|2023|loc="Clinical Presentation"}} Some instead have "microscopic haematuria" – small amounts of blood in the urine that can only be seen under a microscope during [[urinalysis]] – pain while urinating, or no symptoms at all (their tumors are detected during unrelated [[medical imaging]]).{{sfn|Dyrskjøt|Hansel|Efstathiou|Knowles|2023|loc="Clinical Presentation"}}{{sfn|Lenis|Lec|Chamie|2020|p=1981}} Less commonly, a tumor can block the flow of urine into the bladder; backed up urine can cause the [[Hydronephrosis|kidneys to swell]] resulting in pain along the flank of the body between the ribs and the hips.{{sfn|Hahn|2022|loc="Clinical Presentation and Diagnostic Workup"}} 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.{{sfn|Dyrskjøt|Hansel|Efstathiou|Knowles|2023|loc="Clinical Presentation"}} Women with bladder cancer and haematuria are often misdiagnosed with [[urinary tract infection]]s, delaying appropriate diagnosis and treatment.{{sfn|Lenis|Lec|Chamie|2020|p=1981}} 

Around 3% of people with bladder cancer have tumors that have already spread (metastasized) outside the bladder at the time of diagnosis.{{sfn|Hahn|2022|loc="Staging and Outcomes by Stage"}} Bladder cancer most commonly spreads to the bones, lungs, liver, and nearby [[lymph node]]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 [[bone fracture|fractures]]. Lung tumors can cause persistent cough, [[hemoptysis|coughing up blood]], breathlessness, or recurrent chest infections. Cancer that has spread to the liver can cause general [[malaise]], loss of appetite, weight loss, abdominal pain or [[Ascites|swelling]], [[jaundice]] (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.<ref>{{cite web|url=https://www.cancerresearchuk.org/about-cancer/bladder-cancer/metastatic/symptoms |access-date=11 November 2024 |title=Symptoms of Metastatic Bladder Cancer |publisher=Cancer Research UK |date=14 March 2023}}</ref>

==Diagnosis==

Those suspected of having bladder cancer undergo several tests to assess the presence and extent of any tumors. The [[Gold standard (test)|gold standard]] is [[cystoscopy]], wherein a flexible camera is threaded through the [[urethra]] and into the bladder to visually inspect for cancerous tissue.<ref name=ACS-tests/>{{sfn|Dyrskjøt|Hansel|Efstathiou|Knowles|2023|loc="Diagnosis and Screening"}} 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]] (CIS).{{sfn|Ahmadi|Duddalwar|Daneshmand|2021|pp=532–533}} 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.<ref name=ACS-tests/>{{sfn|Ahmadi|Duddalwar|Daneshmand|2021|pp=532–533}}

[[File:Blue light cystoscopy CIS.jpg|thumb|A bladder tumor (bottom image, pink) visible in blue light cystoscopy, but not conventional white light cystoscopy (top)]]

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.<ref name=ACS-tests/>{{sfn|Lenis|Lec|Chamie|2020|p=1982}} 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.{{sfn|Lenis|Lec|Chamie|2020|p=1982}}

Several non-invasive tests are available to support the diagnosis. First, many undergo a physical examination that can involve a [[digital rectal exam]] and [[pelvic exam]], where a doctor feels the pelvic area for unusual masses that could be tumors.<ref name=ACS-tests>{{cite web|url=https://www.cancer.org/cancer/types/bladder-cancer/detection-diagnosis-staging/how-diagnosed.html |access-date=8 August 2024 |title=Tests for Bladder Cancer |publisher=American Cancer Society |date=12 March 2024}}</ref> Severe bladder tumors often shed cells into the urine; these can be detected by [[urine cytology]], where cells are collected from a urine sample, and viewed under a [[microscope]].<ref name=ACS-tests/>{{sfn|Dyrskjøt|Hansel|Efstathiou|Knowles|2023|loc="Diagnosis and Screening"}} Cytology can detect around two thirds of [[grading (tumors)|high-grade]] tumors, but detects just 1 in 8 low-grade tumors.{{sfn|Ahmadi|Duddalwar|Daneshmand|2021|loc="Urine Cytology and Other Urine-Based Tumor Markers}} Additional urine tests can be used to detect molecules associated with bladder cancer. Some detect the [[bladder tumor antigen]] (BTA) protein, or [[NMP22]] that tend to be elevated in the urine of those with bladder cancer; some detect the [[mRNA]] of tumor-associated genes; some use [[fluorescence microscopy]] to detect cancerous cells, which is more [[Sensitivity and specificity|sensitive]] than regular microscopy.{{sfn|Ahmadi|Duddalwar|Daneshmand|2021|loc="Urine Cytology and Other Urine-Based Tumor Markers}}

The upper urinary tract ([[ureter]]s and [[kidney]]) 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 [[Computed tomography urography|CT scanning]]. Those whose kidneys are not functioning well enough to filter the dye may instead be scanned by [[magnetic resonance imaging|MRI]].{{sfn|Hahn|2022|loc="Clinical Presentation and Diagnostic Workup"}} Alternatively, the upper urinary tract can be imaged with [[Medical ultrasound|ultrasound]].<ref name=ACS-tests/>

===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]].{{sfn|Dyrskjøt|Hansel|Efstathiou|Knowles|2023|loc="Tissue-Based Diagnosis of Bladder Cancer"}}<ref name=CRUK-Types>{{cite web|url=https://www.cancerresearchuk.org/about-cancer/bladder-cancer/types-stages-grades/types |access-date=26 August 2024 |title=Types of Bladder Cancer |publisher=Cancer Research UK |date=22 September 2024}}</ref> Around 5% of cases are [[squamous cell cancer]] (from a rarer cell in the bladder lining), which are less rare in countries where [[schistosomiasis]] occurs.<ref name=CRUK-Types/> Up to 2% of cases are [[adenocarcinoma]] (from [[mucus]]-producing gland cells).<ref name=CRUK-Types/> The remaining cases are [[sarcoma]]s (from the bladder muscle) or [[small-cell cancer]] (from [[neuroendocrine cell]]s), both of which are relatively rare.<ref name=CRUK-Types/>

The pathologist also [[cancer grading|grades]] 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).{{sfn|Dyrskjøt|Hansel|Efstathiou|Knowles|2023|loc="Tissue-Based Diagnosis of Bladder Cancer"}}

===Staging===
[[File:Diagram showing the T stages of bladder cancer CRUK 372.svg|thumb|Diagram showing the [[TNM staging system|T stages]] of bladder cancer]]

A bladder cancer case is assigned a [[cancer staging|stage]] based on the [[TNM system]].{{sfn|Dyrskjøt|Hansel|Efstathiou|Knowles|2023|loc="Tissue-Based Diagnosis of Bladder Cancer"}} 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).<ref name=CRUK-Stage>{{cite web|url=https://www.cancerresearchuk.org/about-cancer/bladder-cancer/types-stages-grades/stages |access-date=29 August 2024 |title=Stages of Bladder Cancer |publisher=Cancer Research UK |date=22 September 2022}}</ref> 

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).<ref name=CRUK-Stage/> 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.<ref name=CRUK-Stage/> The M score designates spread to distant organs: M0 for a tumor that has not spread; M1 for one that has.<ref name=CRUK-Stage/> 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.{{sfn|Hahn|2022|loc="Staging and Outcomes by Stage"}}

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.{{sfn|Hahn|2022|loc="Staging and Outcomes by Stage"}}

{| class="wikitable" style="text-align:center"
|+ Bladder cancer TNM scores, stage, and [[5-year survival]]{{sfn|Hahn|2022|loc="Figure 86-2"}}
!Stage
!T
!N
!M
!5-year survival
|-
|0
|Tis/Ta
|N0
|M0
|96%
|-
|1
|T1
|N0
|M0
|90%
|-
|2
|T2
|N0
|M0
|70%
|-
|3
|T3
|N0
|M0
|50%
|-
|3
|Any T
|N1-3
|M0
|36%
|-
|4
|Any T
|Any N
|M1
|5%
|}

==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.{{sfn|Hahn|2022|loc="Early-Stage Disease"}}{{sfn|Dyrskjøt|Hansel|Efstathiou|Knowles|2023|loc="TURBT and En Bloc Resection of Bladder Tumor"}} For those with a relatively low risk of tumors recurring, a single bladder injection of chemotherapy ([[mitomycin C]], [[epirubicin]], or [[gemcitabine]]) reduces the risk of tumors regrowing by about 40%.{{sfn|Lenis|Lec|Chamie|2020|p=1980}} Those with higher risk are instead treated with bladder injections of the [[BCG vaccine]] (a live bacterial vaccine, traditionally used for [[tuberculosis]]), administered weekly for six weeks. This nearly halves the rate of tumor recurrence.{{sfn|Hahn|2022|loc="Early-Stage Disease"}} Recurrence risk is further reduced by a series of "maintenance" BCG injections, given regularly for at least a year.{{sfn|Hahn|2022|loc="Early-Stage Disease"}}{{sfn|Dyrskjøt|Hansel|Efstathiou|Knowles|2023|loc="Intravesical Therapy for NMIBC"}} Tumors that do not respond to BCG may be treated with the alternative immune stimulants [[nadofaragene firadenovec]] (sold as "Adstiladrin", a [[gene therapy]] that makes bladder cells produce an [[immunostimulant]] protein), [[nogapendekin alfa inbakicept]] ("Anktiva", a combination of immunostimulant proteins), or [[pembrolizumab]] ("Keytruda", an [[immune checkpoint inhibitor]]).<ref name=ACS-Treat>{{cite web|url=https://www.cancer.org/cancer/types/bladder-cancer/treating/by-stage.html |publisher=American Cancer Society |title=Treatment of Bladder Cancer, Based on Stage and Other Factors |date=1 May 2024}}</ref>

[[File:Diagram showing bladder reconstruction CRUK 111.svg|thumb|Surgical reconstruction after radical cystectomy, using a piece of small intestine to serve as a [[neobladder|new bladder]].]]

People whose tumors continue to grow are often treated with surgery to remove the bladder and surrounding organs, called [[radical cystectomy]].{{sfn|Dyrskjøt|Hansel|Efstathiou|Knowles|2023|loc="Radical Cystectomy"}} The bladder, several adjacent [[lymph node]]s, the lower [[ureter]]s, and nearby internal genital organs – in men the [[prostate]] and [[seminal vesicles]]; in women the [[womb]] and part of the [[vagina]]l wall – are all removed.{{sfn|Dyrskjøt|Hansel|Efstathiou|Knowles|2023|loc="Radical Cystectomy"}} 

Surgeons then construct a new way for urine to leave the body. The most common method is by [[ileal conduit urinary diversion|ileal conduit]], where a piece of the [[ileum]] (part of the small intestine) is removed and used to transport urine from the ureters to a new surgical opening ([[stoma]]) in the abdomen. Urine drains passively into an [[ostomy bag]] worn outside the body, which can be emptied regularly by the wearer.<ref>{{cite web|url=https://www.cancerresearchuk.org/about-cancer/bladder-cancer/treatment/invasive/surgery/removing-bladder |access-date=16 September 2024 |title=Surgery to Remove the Bladder (Cystectomy) |publisher=Cancer Research UK |date=11 November 2022}}</ref> Alternatively, one can have a [[continent urinary diversion]], 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]] – passing a narrow tube through the stoma.<ref>{{cite web|url=https://www.cancerresearchuk.org/about-cancer/bladder-cancer/treatment/invasive/surgery/continent-urinary-diversion |access-date=17 September 2024 |title=Continent Urinary Diversion (Internal Pouch) |publisher=Cancer Research UK |date=24 November 2022}}</ref>{{sfn|Hahn|2022|loc="Muscle-Invasive Disease"}} 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.<ref>{{cite web|url=https://www.cancerresearchuk.org/about-cancer/bladder-cancer/treatment/invasive/surgery/bladder-reconstruction |access-date=17 September 2024 |title=Bladder Reconstruction (Neobladder) |publisher=Cancer Research UK |date=25 November 2024}}</ref>

Those not well enough or unwilling to undergo radical cystectomy may instead benefit from further bladder injections of chemotherapy – [[mitomycin C]], [[gemcitabine]], [[docetaxel]], or [[valrubicin]] – or [[intravenous injection]] of [[pembrolizumab]].{{sfn|Hahn|2022|loc="Early-Stage Disease"}} Around 1 in 5 people with NMIBC will eventually progress to MIBC.{{sfn|Teoh|Kamat|Black|Grivas|2022|p=280}}
Most people with muscle-invasive bladder cancer are treated with radical cystectomy, which cures around half of those affected.{{sfn|Hahn|2022|loc="Muscle-Invasive Disease"}} Treating with chemotherapy prior to surgery (called "[[neoadjuvant therapy]]") using a [[cisplatin]]-containing drug combination (gemcitabine plus cisplatin; or [[methotrexate]], vinblastine, [[doxorubicin]], and cisplatin) improves survival an additional 5 to 10%.{{sfn|Hahn|2022|loc="Muscle-Invasive Disease"}}{{sfn|Dyrskjøt|Hansel|Efstathiou|Knowles|2023|loc="Perioperative Systemic Therapy"}}

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.{{sfn|Hahn|2022|loc="Muscle-Invasive Disease"}} Those with no CIS or urinary blockage may undergo TURBT to remove visible tumors, followed by chemotherapy and [[radiotherapy]], known as "trimodality therapy".<ref name="ACS-May2024">{{cite web |title=Treatment of Bladder Cancer, Based on the Stage and Other Factors |url=https://www.cancer.org/cancer/types/bladder-cancer/treating/by-stage.html |website=www.cancer.org |publisher=American Cancer Society |access-date=11 January 2025 |date=May 1, 2024}}</ref> Around two thirds of these people are cured.{{sfn|Hahn|2022|loc="Muscle-Invasive Disease"}} 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.<ref>{{cite web|url=https://www.cancer.org/cancer/types/bladder-cancer/after-treatment/follow-up.html |access-date=15 November 2024 |title=Living as a Bladder Cancer Survivor |publisher=American Cancer Society |date=12 March 2024}}</ref> If cancer is found in lymph nodes removed during surgery, or there is high risk of recurrence, radiotherapy may be given after surgery.<ref name="ACS-May2024" /> Recurrent bladder tumors are treated with radical cystectomy. Tumor recurrences elsewhere are treated as metastatic bladder cancer.{{sfn|Hahn|2022|loc="Muscle-Invasive Disease"}}

===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.<ref name="ACS-May2024" />

The 2022 [[standard of care]] for metastatic bladder cancer is combination treatment with the chemotherapy drugs [[cisplatin]] and [[gemcitabine]]<!--3-week cycles, find source-->.{{sfn|Compérat|Amin|Cathomas|Choudhury|2022|pp=1717–1718}} The average person on this combination survives around a year, though 15% experience remission, with survival over five years.{{sfn|Hahn|2022|loc="Metastatic Disease"}}{{sfn|Compérat|Amin|Cathomas|Choudhury|2022|pp=1717–1718}} Around half of those with metastatic bladder cancer are in too poor health to receive cisplatin. They instead receive the related drug [[carboplatin]] along with gemcitabine; the average person on this regimen survives around 9 months.{{sfn|Hahn|2022|loc="Metastatic Disease"}} Those whose disease responds to chemotherapy benefit from switching to immune checkpoint inhibitors [[pembrolizumab]] or [[atezolizumab]] ("Tecentriq") for long-term [[maintenance therapy]].{{sfn|Dyrskjøt|Hansel|Efstathiou|Knowles|2023|loc="Systemic Therapy for Metastatic Bladder Cancer"}} 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.{{sfn|Lopez-Beltran|Cookson|Guercio|Cheng|2024|loc="Treatment of Metastatic Bladder Cancer"}}

Alternate treatment options might include:
* the immunotherapy drug pembrolizumab (Keytruda) combined with the [[Antibody–drug conjugate|antibody-drug conjugate (ADC)]] enfortumab vedotin (Padcev).<ref name="NCI:BC-Stage">{{cite web |title=Treatment of Bladder Cancer by Stage |url=https://www.cancer.gov/types/bladder/treatment/by-stage |website=www.cancer.gov |publisher=National Cancer Institute |access-date=29 January 2025 |date=September 12, 2024 |quote=''Treatment of Bladder Cancer by Stage'' was originally published by the National Cancer Institute.}}</ref> This combination has also been recommended as a first-line therapy in place of chemotherapy.{{sfn|Lopez-Beltran|Cookson|Guercio|Cheng|2024|loc="Treatment of Metastatic Bladder Cancer"}}
* the immunotherapy drug [[nivolumab]] (Opdivo) in conjunction with chemotherapy<ref name="NCI:BC-Stage" />
* chemotherapy, followed by the immunotherapy drug [[avelumab]] (Bavencio)<ref name="NCI:BC-Stage" />

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]]).{{sfn|Lopez-Beltran|Cookson|Guercio|Cheng|2024|loc="Treatment of Metastatic Bladder Cancer"}}<ref>{{cite web|url=https://www.fiercepharma.com/pharma/gilead-withdraws-trodelvy-bladder-cancer-after-trial-flop |access-date=15 November 2024 |title=Gilead Pulls Trodelvy's Approval in Bladder Cancer after Trial Flop, FDA Discussions |publisher=Fierce Pharma |date=18 October 2024}}</ref> Those with genetic alterations that activate the proteins [[FGFR|FGFR2 or FGFR3]] (around 20% of those with metastatic bladder cancer) can also benefit from the FGFR inhibitor [[erdafitinib]] ("Balversa").{{sfn|Lopez-Beltran|Cookson|Guercio|Cheng|2024|loc="Treatment of Metastatic Bladder Cancer"}}

Bladder cancer that continues growing can be treated with second-line chemotherapies. [[Vinflunine]] is used in Europe, while [[paclitaxel]], [[docetaxel]], and [[pemetrexed]] are used in the United States; only a minority of those treated improve on these therapies.{{sfn|Smith|Balar|Milowsky|Chen|2020|p=1398}}

If medicines are no longer controlling the cancer, other treatments may still be helpful, e.g., [[palliative care]] that focuses on preventing or relieving problems the cancer may cause.<ref name="ACS-May2024" />

Because metastatic bladder cancers are rarely cured by current treatment methods, many experts suggest considering [[clinical trial]]s evaluating alternative treatments.<ref name="ACS-May2024" />

===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%).{{sfn|Lenis|Lec|Chamie|2020|p=1986}} 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.{{sfn|Lenis|Lec|Chamie|2020|p=1986}}

Rerouting the ureters, urinary diversions, can cause permanent metabolic issues. The piece of ileum used to reroute urine flow can absorb more [[ion]]s from the urine than the original bladder would, resulting in [[metabolic acidosis]] (blood becoming too acidic), which can be treated with [[sodium bicarbonate]].{{sfn|Lenis|Lec|Chamie|2020|p=1986}}

Shortening the small intestine can result in reduced [[vitamin B12]] absorption, which can be treated with oral vitamin B12 supplementation.{{sfn|Lenis|Lec|Chamie|2020|p=1986}} Issues with the new urine system can cause urinary retention, which can [[hydronephrosis|damage the ureters and kidneys]] and increase one's risk of urinary tract infection.{{sfn|Lenis|Lec|Chamie|2020|p=1986}}

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]].<ref>{{cite web |title=Chemotherapy for Cervical Cancer |url=https://www.cancer.org/cancer/types/cervical-cancer/treating/chemotherapy.html |website=www.cancer.org |publisher=American Cancer Society |access-date=24 October 2024 |date=June 28, 2024}}</ref>

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.<ref>{{cite web |title=Immunotherapy Side Effects |url=https://www.cancer.gov/about-cancer/treatment/types/immunotherapy/side-effects |website=www.cancer.gov |publisher=National Cancer Institute |access-date=29 January 2025 |date=February 16, 2023 |quote=''Immunotherapy Side Effects'' was originally published by the National Cancer Institute.}}</ref> Some people might have [[Intravenous therapy#Adverse effects|allergic reactions]] 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.<ref name="ACS-October2024">{{cite web |title=Immunotherapy for Bladder Cancer |url=https://www.cancer.org/cancer/types/bladder-cancer/treating/immunotherapy-for-bladder-cancer.html |website=www.cancer.org |publisher=American Cancer Society |access-date=12 January 2025 |date=October 30, 2024}}</ref>

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.<ref>{{cite web |title=Targeted Therapy to Treat Cancer |url=https://www.cancer.gov/about-cancer/treatment/types/targeted-therapies |website=www.cancer.gov |publisher=National Cancer Institute |access-date=29 January 2025 |date=May 31, 2022 |quote=''Targeted Therapy to Treat Cancer'' was originally published by the National Cancer Institute.}}</ref>

Radiotherapy acute side effects involve the gastrointestinal system, e.g., diarrhea and constipation; the urinary tract; and may cause [[cervicitis]]. Common late effects include: [[Primary ovarian insufficiency|premature ovarian failure]]; [[telangiectasias]], and subsequent hemorrhage; and [[myelopathy|progressive myelopathy]].<ref name="Majeed2023">{{cite book |last1=Majeed |first1=Hafsa |last2=Gupta |first2=Vikas |title=Adverse Effects of Radiation Therapy |date=August 14, 2023 |publisher=StatPearls Publishing LLC. |url=https://www.ncbi.nlm.nih.gov/books/NBK563259/ |pmid=33085406 |id=NBK563259 |access-date=24 October 2024}}</ref> Pelvic radiotherapy late effects (with occurrence rates) include [[osteonecrosis]] (8-20%), [[vaginal stenosis]] (>2.5%)<ref name="LateEffects2023">{{cite journal |last1=Schmitt |first1=Luiza G. |last2=Amarnath |first2=Sudha R. |title=Late Effects of Pelvic Radiation Therapy in the Female Patient: A Comprehensive Review |journal=Applied Radiation Oncology |date=September 1, 2023 |volume=2023 |issue=3 |pages=13–24 |doi=10.37549/ARO-D-23-00016 |url=https://www.appliedradiationoncology.com/articles/late-effects-of-pelvic-radiation-therapy-in-the-female-patient-a-comprehensive-review |access-date=16 October 2024|url-access=subscription }}</ref> and chronic [[Radiation enteropathy|pelvic radiation disease]] (1-10%), e.g., [[Radiation-induced lumbar plexopathy|lumbosacral plexopathy]].<ref name="CCR-19-2744">{{cite journal |last1=Huh |first1=Jung Wook |last2=Tanksley |first2=Jarred |last3=Chino |first3=Junzo |last4=Willett |first4=Christopher G. |last5=Dewhirst |first5=Mark W. |title=Long-term Consequences of Pelvic Irradiation: Toxicities, Challenges, and Therapeutic Opportunities with Pharmacologic Mitigators |journal=Clinical Cancer Research |date=July 1, 2020 |volume=26 |issue=13 |pages=3079–3090 |doi=10.1158/1078-0432.CCR-19-2744 |pmid=32098770 |url=https://aacrjournals.org/clincancerres/article/26/13/3079/82622/Long-term-Consequences-of-Pelvic-Irradiation |access-date=24 October 2024 |issn=1078-0432|url-access=subscription }}</ref> Radiation also induces secondary malignancies such as [[leukemia]], [[lymphoma]], bone and [[soft-tissue sarcoma]] with occurrence rates between 0.2-1.0% per year for each.<ref name="Majeed2023" /> See also: [[Radiation therapy#Side effects]].

==Causes==

Bladder cancer is caused by changes to the [[DNA]] of bladder cells that result in those cells growing uncontrollably.<ref name=ACS-Cause/> These changes can be random, or can be induced by exposure to toxic substances such as those from consuming tobacco.<ref>{{cite web|url=https://www.cancerresearchuk.org/about-cancer/what-is-cancer/how-cancer-starts |access-date=24 October 2024 |title=How Does Cancer Start |publisher=Cancer Research UK |date=6 October 2023}}</ref> 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.<ref name=ACS-Cause>{{cite web|url=https://www.cancer.org/cancer/types/bladder-cancer/causes-risks-prevention/what-causes.html |access-date=2 July 2024 |title=What Causes Bladder Cancer? |publisher=American Cancer Society |date=12 March 2024}}</ref> Cancer cells accumulate further [[mutation|DNA changes]] as they multiply, which can allow the tumor to evade the [[immune system]], resist regular [[cell death pathway]]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.{{fact|date=December 2024}}

===Smoking===

[[Tobacco smoking]] is the main contributor to bladder cancer risk; around half of bladder cancer cases are estimated to be caused by smoking.{{sfn|Hahn|2022|loc="Risk Factors"}}{{sfn|Jubber|Ong|Bukavina|Black|2023|loc="3.2.1. Smoking"}} Tobacco smoke contains [[carcinogen]]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.<ref>{{cite web|url=https://www.nhs.uk/conditions/bladder-cancer/causes/ |access-date=16 October 2024 |title=Causes – Bladder Cancer |publisher = National Health Service |date=1 July 2021}}</ref> Bladder cancer risk rises both with number of cigarettes smoked per day, and with duration of smoking habit.{{sfn|Jubber|Ong|Bukavina|Black|2023|loc="3.2.1. Smoking"}} Those who smoke also tend to have an increased risk of treatment failure, metastasis, and death.{{sfn|Lobo|Afferi|Moschini|Mostafid|2022|loc="3.2.1. Tobacco Smoking"}} The risk of developing bladder cancer decreases in those who [[smoking cessation|quit smoking]], falling by 30% after five years of smoking abstention.{{sfn|Van Hoogstraten|Vrieling|Van der Heijden|Kogevinas|2023|pp=291–292}} However, the risk will remain higher than those who have never smoked before.{{sfn|Jubber|Ong|Bukavina|Black|2023|loc="3.2.1. Smoking"}} Because development of bladder cancer takes many years, it is not yet known if use of [[electronic cigarette]]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.{{sfn|Van Hoogstraten|Vrieling|Van der Heijden|Kogevinas|2023|pp=292–293}}

===Occupational exposure===

Up to 10% of bladder cancer cases are caused by workplace exposure to toxic chemicals.{{sfn|Lobo|Afferi|Moschini|Mostafid|2022|loc="3.2.2. Occupational carcinogen exposure"}} Exposure to certain [[aromatic amine]]s, namely [[benzidine]], [[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.{{sfn|Van Hoogstraten|Vrieling|Van der Heijden|Kogevinas|2023|p=295}}{{sfn|Dyrskjøt|Hansel|Efstathiou|Knowles|2023|loc="Occupational exposure"}} The [[International Agency for Research on Cancer]] further classifies rubber processing, aluminum production, and firefighting as occupations that increase one's risk of developing bladder cancer.{{sfn|Van Hoogstraten|Vrieling|Van der Heijden|Kogevinas|2023|p=295}} Exposure to [[arsenic]] – either through workplace exposure or through drinking water in places where [[Arsenic contamination of groundwater|arsenic naturally contaminates groundwater]] –  is also commonly linked to bladder cancer risk.{{sfn|Van Hoogstraten|Vrieling|Van der Heijden|Kogevinas|2023|p=295}} 

===Medical conditions===

Chronic bladder infections can increase one's risk of developing bladder cancer. Most prominent is [[schistosomiasis]], in which the eggs of the flatworm ''[[Schistosoma haematobium]]'' can become lodged in the bladder wall, causing chronic bladder inflammation and repeated bladder infections.{{sfn|Van Hoogstraten|Vrieling|Van der Heijden|Kogevinas|2023|p=296}} In places with [[Endemic (epidemiology)|endemic]] schistosomiasis, up to 16% of bladder cancer cases are caused by prior Schistosoma infection.{{sfn|Van Hoogstraten|Vrieling|Van der Heijden|Kogevinas|2023|p=296}} Worms can be cleared by treatment with [[praziquantel]], which reduces bladder cancer cases in schistosomiasis endemic areas.{{sfn|Van Hoogstraten|Vrieling|Van der Heijden|Kogevinas|2023|p=296}}{{sfn|Dyrskjøt|Hansel|Efstathiou|Knowles|2023|loc="Epidemiology"}} Similarly, those with long-term [[indwelling catheter]]s are at risk for repeated urinary tract infections, and have increased risk of developing bladder cancer.{{sfn|Lopez-Beltran|Cookson|Guercio|Cheng|2024|loc="Epidemiology"}}

Some medical treatments are also known to increase bladder cancer risk. As many as 16% of those treated with the chemotherapeutic [[cyclophosphamide]] go on to develop bladder cancer within 15 years of their treatment.{{sfn|Mossanen|2021|p=449}} 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.{{sfn|Mossanen|2021|p=449}} Long-term use of the medication [[pioglitazone]] for [[type 2 diabetes]] may increase bladder cancer risk.{{sfn|Hahn|2022|loc="Clinical Epidemiology and Risk Factors"}}

===Genetics===
Bladder cancer does not typically run in families.{{sfn|Van Hoogstraten|Vrieling|Van der Heijden|Kogevinas|2023|p=295}} Only 4% of those diagnosed with bladder cancer have a parent or sibling with the disease,{{sfn|Jubber|Ong|Bukavina|Black|2023|loc="3.2. Risk Factors for BC"}} potentially inheriting a gene syndrome associated with bladder cancer, for example:<ref name="ACS-March2024">{{cite web |title=Bladder Cancer Risk Factors |url=https://www.cancer.org/cancer/types/bladder-cancer/causes-risks-prevention/risk-factors.html |website=www.cancer.org |publisher=American Cancer Society |access-date=12 January 2025 |date=March 12, 2024}}</ref>{{sfn|Hahn|2022|loc="Clinical Epidemiology and Risk Factors"}}
* Mutations of the [[Retinoblastoma protein|RB1 gene]], while associated with 95% of [[Retinoblastoma]] cases,<ref name="PMID:34407969">{{cite journal |last1=Mandigo |first1=Amy C |last2=Tomlins |first2=Scott A |last3=Kelly |first3=William K |last4=Knudsen |first4=Karen E |title=Relevance of pRB Loss in Human Malignancies |journal=Clinical Cancer Research |date=January 19, 2022 |volume=28 |issue=2 |page=Table 1 |doi=10.1158/1078-0432.CCR-21-1565 |pmid=34407969 |pmc=9306333 }}</ref> are also linked with bladder cancer.<ref name="ACS-March2024" />
* [[Cowden disease]] is caused by mutations in the [[PTEN (gene)|PTEN gene]]; see [[Cowden syndrome#Genetics]].  People with this syndrome have increased risk of developing several cancers, including bladder cancer.{{sfn|Hahn|2022|loc="Clinical Epidemiology and Risk Factors"}}
* [[Lynch syndrome]] is caused by mutations in [[DNA mismatch repair]] genes [[MLH1]], [[MSH2]], [[MSH6]] or [[PMS2]]; see main article [[Hereditary nonpolyposis colorectal cancer]] (HNPCC). People with this syndrome have increased risk of developing several cancers, including bladder{{sfn|Hahn|2022|loc="Clinical Epidemiology and Risk Factors"}} and urinary tract cancers.<ref name="ACS-March2024" />

Large population studies have identified additional [[gene variant]]s that each slightly increase bladder cancer risk. Most of these are variants in genes involved in metabolism of carcinogens ([[NAT2]], [[GSTM1]], and [[UGT1A6]]), controlling cell growth ([[TP63]], [[CCNE1]], [[MYC]], and [[FGFR3]]), or repairing [[DNA damage]] ([[NBN (gene)|NBN]], [[XRCC1]] and [[XRCC3|3]], and [[ERCC2]], [[ERCC4|4]], and [[ERCC5|5]]).{{sfn|Van Hoogstraten|Vrieling|Van der Heijden|Kogevinas|2023|p=295}}

===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]] and [[American Institute for Cancer Research]] 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, [[Legume|legumes]], 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.{{sfn|Van Hoogstraten|Vrieling|Van der Heijden|Kogevinas|2023|p=293}}<ref>{{cite web|title=Diet, Nutrition, Physical Activity and Bladder Cancer |publisher=World Cancer Research Fund, American Institute for Cancer Research |date=2018 |url=https://www.aicr.org/wp-content/uploads/2020/01/bladder-report-2015.pdf |access-date=17 October 2024 |page=20}}</ref> Other studies have indicated a slight increased risk of developing bladder cancer in those who are overweight or [[obese]], as well as a slight decrease in risk for those who undertake high levels of physical activity.{{sfn|Van Hoogstraten|Vrieling|Van der Heijden|Kogevinas|2023|p=293}}

==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]], 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.{{sfn|Dyrskjøt|Hansel|Efstathiou|Knowles|2023|loc="Mechanisms/Pathophysiology"}} 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).{{sfn|Dyrskjøt|Hansel|Efstathiou|Knowles|2023|loc="Mechanisms/Pathophysiology"}}{{sfn|Teoh|Kamat|Black|Grivas|2022|p=285}}

Despite arising from the same tissue, NMIBC and MIBC develop along distinct pathways and bear distinct genetic mutations.{{sfn|Dyrskjøt|Hansel|Efstathiou|Knowles|2023|loc="Mechanisms/Pathophysiology"}} Most NMIBC tumors start as low-grade papillary (finger-like, projecting into the bladder) tumors.{{sfn|Hahn|2022|loc="Molecular Biology"}} Mutations in cell growth pathways are common. Most common are mutations that activate [[FGFR3]] (present in up to 80% of NMIBC tumors).{{sfn|Hahn|2022|loc="Molecular Biology"}} Mutations activating the growth pathway [[PI3K/AKT/mTOR pathway]] are also common, including mutations in [[PIK3CA]] (in around 30% of tumors) and [[ERBB2]]/[[ERBB3]] (up to 15% of tumors), and loss of [[TSC1]] (50% of tumors).{{sfn|Dyrskjøt|Hansel|Efstathiou|Knowles|2023|loc="Mechanisms/Pathophysiology"}} Major regulators of [[chromatin]] (influences the expression of different genes) are inactivated in over 65% of NMIBC tumors.{{sfn|Dyrskjøt|Hansel|Efstathiou|Knowles|2023|loc="Mechanisms/Pathophysiology"}} 

MIBC often starts with low-lying, flat, high-grade tumors, that quickly spread beyond the bladder.{{sfn|Hahn|2022|loc="Molecular Biology"}} These tumors have more genetic mutations and chromosomal abnormalities overall, with mutations more frequent than in any cancer but [[lung cancer]] and [[melanoma]].{{sfn|Dyrskjøt|Hansel|Efstathiou|Knowles|2023|loc="Mechanisms/Pathophysiology"}} Mutations that inactivate the [[tumor suppressor]] genes [[TP53]] and [[Retinoblastoma protein|RB]] are common, as are mutations in [[CDH1 (gene)|CDH1]] (involved in metastasis) and [[VEGFR2]] (involved in cell growth and metastasis).{{sfn|Hahn|2022|loc="Molecular Biology"}}

Some genetic abnormalities are common to NMIBC and MIBC tumors. Around half of each have lost all or part of [[chromosome 9]], which contains several regulators of [[tumor suppressor]] genes.{{sfn|Dyrskjøt|Hansel|Efstathiou|Knowles|2023|loc="Mechanisms/Pathophysiology"}} Up to 80% of tumors have mutations in the gene [[TERT]], which extends cells' [[telomere]]s to allow for extended replication.{{sfn|Dyrskjøt|Hansel|Efstathiou|Knowles|2023|loc="Mechanisms/Pathophysiology"}}

==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-year survival|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.{{sfn|Hahn|2022|loc="Figure 86-2"}}

==Epidemiology==
[[File:Bladder cancer world map - Death - WHO2004.svg|thumb|upright=1.55|[[Age adjustment|Age-standardized]] death from bladder cancer per 100,000&nbsp;inhabitants in 2004.<ref>{{cite web |url=https://www.who.int/healthinfo/global_burden_disease/estimates_country/en/index.html |title=WHO Disease and injury country estimates |year=2009 |work=World Health Organization |access-date=11 November 2009 |url-status=live |archive-url=https://web.archive.org/web/20091111101009/http://www.who.int/healthinfo/global_burden_disease/estimates_country/en/index.html |archive-date=11 November 2009}}</ref>{{Div col|small=yes|colwidth=10em}}
{{legend|#b3b3b3|no data}}
{{legend|#ffff65|less than 1.5}}
{{legend|#fff200|1.5–3}}
{{legend|#ffdc00|3–4.5}}
{{legend|#ffc600|4.5–6}}
{{legend|#ffb000|6–7.5}}
{{legend|#ff9a00|7.5–9}}
{{legend|#ff8400|9–10.5}}
{{legend|#ff6e00|10.5–12}}
{{legend|#ff5800|12–13.5}}
{{legend|#ff4200|13.5–15}}
{{legend|#ff2c00|15–16.5}}
{{legend|#cb0000|more than 16.5}}
{{div col end}}]]

Around 500,000 people are diagnosed with bladder cancer each year, and 200,000 die of the disease.{{sfn|Lenis|Lec|Chamie|2020|p=1980}} This makes bladder cancer the tenth most commonly diagnosed cancer, and the thirteenth cause of cancer deaths.{{sfn|Dyrskjøt|Hansel|Efstathiou|Knowles|2023|loc="Epidemiology"}} 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]] infection is common, such as North Africa.{{sfn|Dyrskjøt|Hansel|Efstathiou|Knowles|2023|loc="Epidemiology"}}

Bladder cancer is much more common in men than women; around 1.1% of men and 0.27% of women develop bladder cancer.{{sfn|Lenis|Lec|Chamie|2020|p=1981}} This makes bladder cancer the sixth most common cancer in men, and the seventeenth in women.{{sfn|Dyrskjøt|Hansel|Efstathiou|Knowles|2023|loc="Introduction"}} When women are diagnosed with bladder cancer, they tend to have more advanced disease and consequently a poorer prognosis.{{sfn|Dyrskjøt|Hansel|Efstathiou|Knowles|2023|loc="Introduction"}} This difference in outcomes is attributed to numerous factors such as difference in carcinogen exposure, [[genetics]], social factors and quality of care.<ref name="Female BC">{{cite journal | vauthors = Marks P, Soave A, Shariat SF, Fajkovic H, Fisch M, Rink M | title = Female with bladder cancer: what and why is there a difference? | journal = Translational Andrology and Urology | volume = 5 | issue = 5 | pages = 668–682 | date = October 2016 | pmid = 27785424 | pmc = 5071204 | doi = 10.21037/tau.2016.03.22 | doi-access = free}}</ref> 

As with most cancers, bladder cancer is more common in older people; the average person with bladder cancer is diagnosed at age 73.{{sfn|Hahn|2022|loc="Introduction"}} 80% of those diagnosed with bladder cancer are 65 or older; 20% are 85 or older.{{sfn|Mossanen|2021|p=448}}

== Veterinary medicine ==
Bladder cancer is relatively rare in domestic dogs and cats. In dogs, around 1% of diagnosed cancers are bladder cancer.{{sfn|Burgess|DeRegis|2019|p=314–317}} [[Shetland sheepdog]]s, [[beagle]]s, and various [[terrier]]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.{{sfn|Burgess|DeRegis|2019|p=314–317}} Urine tests can aid in diagnosis; they test for the protein [[bladder tumor antigen]] (high in bladder tumors) or mutations in the [[BRAF (gene)|BRAF]] gene (present in around 80% of dogs with bladder or prostate cancer).{{sfn|Burgess|DeRegis|2019|p=314–317}} Dogs with confirmed cancer are treated with [[Cyclooxygenase-2 inhibitor|COX-2 inhibitor]] drugs, such as [[piroxicam]], [[deracoxib]], and [[meloxicam]]. These drugs halt disease progression in around 50% of dogs, shrink tumors in around 12%, and eliminate tumors in around 6%.{{sfn|Burgess|DeRegis|2019|p=314–315}} COX-2 inhibitors are often combined with chemotherapy drugs, most commonly [[mitoxantrone]], [[vinblastine]], or [[chlorambucil]].{{sfn|Burgess|DeRegis|2019|p=314–317}} 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.{{sfn|Griffin|Culp|Giuffrida|Ellis|2020|loc="Introduction"}}{{sfn|Griffin|Culp|Giuffrida|Ellis|2020|loc="3.5 Treatment"}}

==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]] (United Kingdom),<ref>{{Cite web |title=Cancer Research UK |url=https://www.cancerresearchuk.org/ |access-date=2025-03-12 |website=Cancer Research UK |language=en}}</ref> [[Fight Bladder Cancer]] (United Kingdom),<ref name=":0">{{Cite web |title=Home |url=https://www.fightbladdercancer.co.uk/ |access-date=2025-03-12 |website=Fight Bladder Cancer |language=en-GB}}</ref> [[Bladder Cancer Advocacy Network]] (United States),<ref>{{Cite web |title=Home |url=https://bcan.org/ |access-date=2025-03-12 |website=Bladder Cancer Advocacy Network |language=en-US}}</ref> and [[The World Bladder Cancer Patient Coalition]] (international),<ref>{{Cite web |title=Home |url=https://worldbladdercancer.org/ |access-date=2025-03-12 |website=World Bladder Cancer Patient Coalition |language=en-US}}</ref> 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.<ref name=":1">{{Cite journal |last1=Iya |first1=Abdulkarim Muhammad |last2=Beyer |first2=Katharina |last3=Kotecha |first3=Pinky |last4=Kibaru |first4=Joyce |last5=Abdullahi |first5=Muzzammil |last6=Alhassan |first6=Sani Usman |last7=Mustapha |first7=Muhammad Inuwa |last8=Ahmad |first8=Abdullahi |last9=Lawal |first9=Yusuf |last10=Rabiu Ibrahim |first10=Jalo |last11=Aminu |first11=Aliyu |last12=Abubakar |first12=Aisha |last13=Saleh |first13=Abdullahi |last14=Bryan |first14=Richard T |last15=Van Hemelrijck |first15=Mieke |date=March 2022 |title=Scoping review: bladder cancer in Nigeria – what are the gaps in clinical care and research? |journal=BMJ Open |language=en |volume=12 |issue=3 |article-number=e049241 |doi=10.1136/bmjopen-2021-049241 |pmid=35260447 |issn=2044-6055 |pmc=8905928 }}</ref><ref name=":0" /> Independent studies and health reports have recognised their role in advancing bladder cancer awareness and care.<ref name=":1" /><ref>{{Cite journal |last1=Boormans |first1=Joost L. |last2=Zwarthoff |first2=Ellen C. |date=2016-01-07 |title=Limited Funds for Bladder Cancer Research and What Can We Do About It |journal=Bladder Cancer |language=en |volume=2 |issue=1 |pages=49–51 |doi=10.3233/BLC-150042 |pmid=27376124 |pmc=4927910 |issn=2352-3727 }}</ref><ref>{{Cite web |title=Personalised radiotherapy for people with bladder cancer shows promise |url=https://www.icr.ac.uk/about-us/icr-news/detail/personalised-radiotherapy-for-people-with-bladder-cancer-shows-promise |access-date=2025-03-12 |website=www.icr.ac.uk |language=en}}</ref>

== References ==
{{Reflist}}

=== Works cited ===
{{refbegin|32em}}
*{{cite journal| vauthors=Ahmadi H, Duddalwar V, Daneshmand S |title=Diagnosis and Staging of Bladder Cancer |journal=Hematol Oncol Clin North Am |volume=35 |issue=3 |pages=531–541 |date=June 2021 |pmid=33958149 |doi=10.1016/j.hoc.2021.02.004 }}
*{{cite journal |vauthors=Burgess KE, DeRegis CJ |title=Urologic Oncology |journal=Vet Clin North Am Small Anim Pract |volume=49 |issue=2 |pages=311–323 |date=March 2019 |pmid=30635132 |doi=10.1016/j.cvsm.2018.11.006 |url=}}
*{{cite journal |vauthors=Compérat E, Amin MB, Cathomas R, Choudhury A, De Santis M, Kamat A, Stenzl A, Thoeny HC, Witjes JA |title=Current best practice for bladder cancer: a narrative review of diagnostics and treatments |journal=Lancet |volume=400 |issue=10364 |pages=1712–1721 |date=November 2022 |pmid= 36174585|doi=10.1016/S0140-6736(22)01188-6 |url=|doi-access=free }}
*{{cite journal |vauthors=Dyrskjøt L, Hansel DE, Efstathiou JA, Knowles MA, Galsky MD, Teoh J, Theodorescu D |title=Bladder cancer |journal=Nat Rev Dis Primers |volume=9 |issue=1 |article-number=58 |date=October 2023 |pmid=37884563 |doi=10.1038/s41572-023-00468-9|pmc=11218610 }}
*{{cite journal |vauthors=Griffin MA, Culp WT, Giuffrida MA, Ellis P, Tuohy J, Perry JA, Gedney A, Lux CN, Milovancev M, Wallace ML, Hash J, Mathews K, Liptak JM, Selmic LE, Singh A, Palm CA, Balsa IM, Mayhew PD, Steffey MA, Rebhun RB, Burton JH, Kent MS |title=Lower urinary tract transitional cell carcinoma in cats: Clinical findings, treatments, and outcomes in 118 cases |journal=J Vet Intern Med |volume=34 |issue=1 |pages=274–282 |date=January 2020 |pmid=31721288 |pmc=6979092 |doi=10.1111/jvim.15656 |url=}}
*{{cite book| vauthors=Hahn NM |chapter=Chapter 86: Cancer of the Bladder and Urinary Tract |title=[[Harrison's Principles of Internal Medicine]] |edition=21st |publisher=McGraw Hill |date=2022|veditors= Loscalzo J, Fauci A, Kasper D, ''et al'' |isbn= 978-1-264-26850-4}}
*{{cite journal |vauthors=Jubber I, Ong S, Bukavina L, Black PC, Compérat E, Kamat AM, Kiemeney L, Lawrentschuk N, Lerner SP, Meeks JJ, Moch H, Necchi A, Panebianco V, Sridhar SS, Znaor A, Catto JW, Cumberbatch MG |title=Epidemiology of Bladder Cancer in 2023: A Systematic Review of Risk Factors |journal=Eur Urol |volume=84 |issue=2 |pages=176–190 |date=August 2023 |pmid=37198015 |doi=10.1016/j.eururo.2023.03.029 |url=|hdl=11573/1696425 |hdl-access=free }}
*{{cite journal |vauthors=Lenis AT, Lec PM, Chamie K |title=Bladder Cancer: A Review |journal=JAMA |volume=324 |issue=19 |pages=1980–1991 |date=November 2020 |pmid=33201207 |doi=10.1001/jama.2020.17598 |url=}}
*{{cite journal |vauthors=Lobo N, Afferi L, Moschini M, Mostafid H, Porten S, Psutka SP, Gupta S, Smith AB, Williams SB, Lotan Y |title=Epidemiology, Screening, and Prevention of Bladder Cancer |journal=Eur Urol Oncol |volume=5 |issue=6 |pages=628–639 |date=December 2022 |pmid=36333236 |doi=10.1016/j.euo.2022.10.003 |url=}}
*{{cite journal |vauthors=Lopez-Beltran A, Cookson MS, Guercio BJ, Cheng L |title=Advances in diagnosis and treatment of bladder cancer |journal=BMJ |volume=384 |issue= |article-number=e076743 |date=February 2024 |pmid=38346808 |doi=10.1136/bmj-2023-076743 |url=}}
*{{cite journal |vauthors=Mossanen M |title=The Epidemiology of Bladder Cancer |journal=Hematol Oncol Clin North Am |volume=35 |issue=3 |pages=445–455 |date=June 2021 |pmid=33958144 |doi=10.1016/j.hoc.2021.02.001 |url=}}
*{{cite book |vauthors=Smith BA, Balar AV, Milowsky MI, Chen RC |chapter=Carcinoma of the Bladder |title=Abeloff's Clinical Oncology |edition=6 |date=2020 |pages=1382–1400 |publisher=Elsevier |isbn=978-0-323-47674-4}}
*{{cite journal |vauthors=Teoh JY, Kamat AM, Black PC, Grivas P, Shariat SF, Babjuk M |title=Recurrence mechanisms of non-muscle-invasive bladder cancer - a clinical perspective |journal=Nat Rev Urol |volume=19 |issue=5 |pages=280–294 |date=May 2022 |pmid=35361927 |doi=10.1038/s41585-022-00578-1 |url=}}
*{{cite journal |vauthors=Van Hoogstraten LM, Vrieling A, Van der Heijden AG, Kogevinas M, Richters A, Kiemeney LA |title=Global trends in the epidemiology of bladder cancer: challenges for public health and clinical practice |journal=Nat Rev Clin Oncol |volume=20 |issue=5 |pages=287–304 |date=May 2023 |pmid=36914746 |doi=10.1038/s41571-023-00744-3 |url=}}
{{refend}}

== External links ==
{{Medical resources
|  DiseasesDB       = 1427
|  ICD10            = {{ICD10|C67}}
|  ICD9             = {{ICD9|188}}
|  ICDO             =
|  OMIM             = 109800
|  MedlinePlus      = 000486
|  eMedicineSubj    = radio
|  eMedicineTopic   = 711
|  eMedicine_mult   = {{eMedicine2|med|2344}} {{eMedicine2|med|3022}}
|  MeshID           = D001749
}}
{{Urologic neoplasia}}
{{Portal bar | Medicine}}
{{Authority control}}

{{DEFAULTSORT:Bladder Cancer}}
[[Category:Bladder cancer| ]]
[[Category:Health effects of tobacco]]
[[Category:Types of cancer]]