Squamous cell carcinoma (SCC) of the urinary bladder is a malignant epithelial tumor exhibiting pure squamous differentiation without a conventional urothelial carcinoma component. It should be distinguished from urothelial carcinoma with squamous differentiation (UCSD), in which squamous differentiation occurs within an otherwise urothelial carcinoma. This distinction is clinically important because histologic subtype influences treatment planning and interpretation of prognosis. ^{[1] [2]}

Bladder SCC is uncommon in most Western populations but represents a substantially larger proportion of bladder malignancies in regions historically affected by urinary schistosomiasis. Its epidemiology varies geographically and reflects differences in environmental exposures and patterns of chronic bladder irritation. ^[3][4]

Compared with urothelial carcinoma, bladder SCC has a more balanced sex distribution, with reported male-to-female ratios of approximately 0.9–1.6:1, compared with approximately 3:1 for urothelial carcinoma. Registry studies also report a higher proportion of female and Black patients among those diagnosed with SCC. These demographic differences are population-level associations and should not be interpreted as individual-level determinants of disease. ^[5][6][7]

Bladder SCC is strongly associated with chronic bladder inflammation and irritation. Important clinical contexts include urogenital infection with *Schistosoma haematobium*, prolonged indwelling urinary catheterization, neurogenic bladder, recurrent urinary tract infection, and bladder calculi. Tobacco use also contributes to bladder cancer risk, although the association between tobacco and pure SCC is less consistent than that established for urothelial carcinoma. The underlying oxidative-stress and chronic-inflammation mechanisms are addressed in the Pathophysiology microchapter. ^[8][9][10]

Patients with bladder SCC frequently present with hematuria and other symptoms related to bladder involvement. Chronic urinary symptoms may also occur in patients with longstanding inflammatory or irritative conditions. Many patients have muscle-invasive disease at diagnosis, and locally advanced tumors are common. ^[11][12][13]

The characteristic clinical pattern is marked local aggressiveness and a high burden of locally advanced disease. However, the extent of regional or distant spread varies by stage and population; SCC should not be assumed to have a uniformly low metastatic potential. ^[14][15]Mercier J, Cornillon P, Barthélémy P, et al. Squamous cell carcinoma of the bladder: current evidence, therapeutic challenges, and research perspectives from the French AVENTUR Group. *Crit Rev Oncol Hematol*. 2026;225:105505. doi:10.1016/j.critrevonc.2026.105505.^[16]

Its presentation, demographic distribution, and outcomes vary between schistosomal and non-schistosomal populations.

Pure SCC demonstrates malignant squamous differentiation without a conventional urothelial carcinoma component. UCSD contains both urothelial carcinoma and a squamous component. Accurate histopathologic classification is essential because the two entities are not managed identically. ^[17][18]

Unlike urothelial carcinomas, for which the WHO/ISUP low-grade and high-grade framework is commonly used, SCC is generally described by conventional differentiation categories: well differentiated, moderately differentiated, or poorly differentiated. Histologic grade should be interpreted alongside tumor stage, nodal status, lymphovascular invasion, and surgical margin status. ^[19][20]

Prognosis is strongly influenced by tumor stage, regional lymph node involvement, resectability, surgical margins, and treatment. Registry studies have reported worse survival for SCC than for urothelial carcinoma in several populations. In a National Cancer Database analysis of muscle-invasive bladder cancer, SCC was independently associated with poorer survival (adjusted hazard ratio [HR] approximately 1.79). In a California Cancer Registry analysis, SCC was associated with worse disease-specific survival (HR approximately 2.61). These estimates arise from different cohorts and endpoints and should not be interpreted as directly interchangeable. ^[21][22]

The stage-adjusted survival disadvantage is not uniform across all clinical settings. In a SEER analysis, SCC was associated with increased mortality among patients with stage I–II disease who did not undergo upfront cystectomy and among those with stage III–IV disease. However, SCC was not associated with increased mortality among patients with organ-confined stage I–II tumors treated with upfront cystectomy. This suggests that the prognostic effect of squamous histology depends in part on disease extent and treatment context. ^[23]

The independent prognostic significance of squamous differentiation in UCSD remains unsettled. A 2026 propensity score-matched analysis reported worse overall survival for UCSD than for pure urothelial carcinoma (HR 1.52), with survival outcomes not significantly different between UCSD and pure SCC. A 2020 meta-analysis also found that squamous differentiation was associated with poorer disease-free survival. Conversely, an Ontario population-based study found no significant adjusted survival disadvantage for UCSD compared with pure urothelial carcinoma and described a more rapid early disease course for SCC, with survival converging by five years. These differences likely reflect variation in populations, endpoints, case definitions, and adjustment methods; the available evidence does not establish a single universal prognostic effect. ^[24][25]

Management depends on whether the tumor is pure SCC or UCSD, as well as clinical stage, resectability, patient fitness, and treatment goals. For localized or resectable pure SCC, definitive local treatment is central, with surgery or selected multimodal approaches considered by a multidisciplinary team. Evidence supporting perioperative systemic chemotherapy in pure SCC remains limited, and a proven role for neoadjuvant or adjuvant chemotherapy has not been established. ^[26]

For advanced or metastatic pure SCC, enrollment in a clinical trial is preferred when available. For selected patients, combination chemotherapy such as cisplatin, ifosfamide, and paclitaxel may be considered. Postoperative radiotherapy may be an option in selected circumstances, including positive surgical margins. Detailed treatment selection and regimen-specific evidence are addressed in the Medical therapy microchapter.^[27]

UCSD should not automatically be managed according to the pure-SCC pathway. Because UCSD retains a urothelial carcinoma component, NCCN advises treatment in a manner similar to pure urothelial carcinoma, while recognizing its potential for a more aggressive natural history. Management should be individualized according to stage, histology, patient factors, and multidisciplinary assessment. ^[28]

– Distinguish pure bladder SCC from urothelial carcinoma with squamous differentiation because the distinction affects treatment planning. – Consider chronic bladder irritation, urinary schistosomiasis, prolonged catheterization, neurogenic bladder, recurrent urinary infection, and bladder calculi when assessing relevant risk factors. – Expect a near-equal sex ratio and a higher proportion of female and Black patients than in urothelial carcinoma cohorts. – Recognize the frequent presentation with muscle-invasive or locally advanced disease and the importance of local control. – Interpret stage-adjusted survival estimates in the context of disease extent and treatment; the survival disadvantage is not uniform across all stages and treatment settings. – Recognize that the independent prognostic effect of squamous differentiation in UCSD remains controversial. – Refer advanced pure SCC for clinical-trial consideration when feasible, and individualize treatment through multidisciplinary review.

Association between bladder cancer and environmental carcinogens is first discovered in 1895. First cystectomy is performed as a treatment for bladder cancer in in 1877. Radium is first used as a treatment of bladder tumors in 1903. Neoadjuvant chemotherapy including methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) is first described in 1985. FDA approved the use of live bacterium, Bacillus Calmette-Guérin (BCG) for treatment and prevent the recurrence of superficial tumors in 1990.

• Cystoscope was first discovered by Maximilian Nitze, a German urologist, in 1877.^[1]
• Association between bladder cancer and environmental carcinogens is first discovered in 1895.
• Urine cytology is first described in 1945.^[2]
• Micropapillary bladder cancer is first described in 1982.^[3]
• Approximately 356,000 new bladder cancer cases of bladder cancer are reported in 2002 worldwide.^[4]

• First cystectomy is performed as a treatment for bladder cancer in in 1877.
• Radium is first used as a treatment of bladder tumors in 1903.^[5]
• Early bladder removal surgery includes removing the bladder (cystectomy) and surrounding tissue where cancer is most likely to spread is performed in 1956.^[6]
• FDA approves the first chemotherapy drug cisplatin for treatment of bladder tumors in 1978.
• Reconstructive bladder surgery in introduced in 1980-1985.
• Neoadjuvant chemotherapy including methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) is first described in 1985.^[7]
• Intravesical chemotherapy using mitomycin to reduce risk of bladder cancer’s recurrence is discovered in 1988.^[8]
• FDA approved the use of live bacterium, bacillus Calmette-Guérin (BCG) for treatment and prevent the recurrence of superficial tumors in 1990.^[9]
• New chemotherapy combination regimen including gemcitabine with cisplatin is introduced as more effective with less side effects compare to MVAC therapy in 2000.^[10]
• New technology that helps to detect cancerous tumors in the bladder that are invisible to the naked eye is discovered in 2016.

Steven C. Campbell, M.D., Ph.D.; Associate Editor(s)-in-Chief: Farima Kahe M.D. [1] Shanshan Cen, M.D. [2]

Bladder cancer may be classified according to the cell types into several subtypes include transitional cell carcinomas, squamous cell carcinomas, adenocarcinomas, small cell carcinoma, lymphoma, and sarcoma.

Bladder cancer may be classified according to the cell types into several subtypes as following:^[1][2][3][4]

• Transitional cell carcinoma (more than 90%)
• Squamous cell carcinoma (2% to 7%)
• Adenocarcinoma (2%)
• Small cell carcinoma
• Lymphoma
• Sarcoma

• Leiomyosarcoma
• Rhabdomyosarcoma
• Angiosarcoma

There are no established causes of bladder cancer.

• There are no established causes of bladder cancer.
• To view the list of risk factors in the development of bladder cancer, please click here.

Bladder cancer must be differentiated from renal cancer, renal stones, prostate cancer, and cystitis.

The most common presentation of bladder cancer is hematuria; however in the advanced cases, the presentation can be bladder mass.

Bladder cancer must be differentiated from other causes of hematuria as in the below table:

Lower abdominal mass can be classified to the gynecological and non-gynecological causes. Bladder cancer in the advanced cases can present as a bladder mass. Below table discusses lower abdominal mass causes:

The prevalence of bladder cancer is approximately 130.5 per 100,000 individuals in the United States. The incidence of bladder cancer is approximately 20.3 per 100,000 individuals in the United States. The incidence of bladder cancer increases with age; the median age at diagnosis is 73 years. Males are more commonly affected with bladder cancer than females. Bladder cancer usually affects individuals of the white race. African American, Asian, and Hispanic individuals are less likely to develop bladder cancer.

• In the United States, the age-adjusted prevalence of bladder cancer is 130.5 per 100,000 persons in 2011.^[1][2]

• The incidence of bladder cancer is approximately 20.3 per 100,000 individuals in the United States, based on 2008-2012 data.^[3][4]

• The delay-adjusted incidence of bladder cancer in 2011 was estimated to be 20.74 per 100,000 persons in the United States.^[1][5]

• In 2011, the age-adjusted incidence of bladder cancer was 20.13 per 100,000 persons in the United States.^[1]

• While the overall age-adjusted incidence of bladder cancer in the United States between 2007 and 2011 is 20.5 per 100,000, the age-adjusted incidence of bladder cancer by age category is:^[1][6]
  • Under 65 years: 5.4 per 100,000
  • 65 and over: 124.7 per 100,000

• The incidence of bladder cancer increases with age; the median age at diagnosis is 73 years.^[3]

• In the United States, the age-adjusted prevalence of bladder cancer by gender in 2011 is:^[1][7]
  • In males: 228.9 per 100,000
  • In females: 56.6 per 100,000

• In the United States, the delay-adjusted incidence of bladder cancer by gender in 2011 is:^[1][8]
  • In males: 36.24 per 100,000 persons
  • In females: 8.98 per 100,000 persons

• In the United States, the age-adjusted incidence of bladder cancer by gender on 2011 is:^[1][9]
  • In males: 35.18 per 100,000 persons
  • In females: 8.72 per 100,000 persons

• Shown below is an image depicting the delay-adjusted incidence and observed incidence of bladder cancer by gender and race in the United States between 1975 and 2011. These graphs are adapted from SEER: The Surveillance, Epidemiology, and End Results Program of the National Cancer Institute.^[1]

<figure-inline class=”mw-default-size”></figure-inline>

• Shown below is a table depicting the age-adjusted prevalence of bladder cancer by race in 2011 in the United States.^[1]

• Shown below is an image depicting the incidence of bladder cancer by race in the United States between 1975 and 2011.^[1]

<figure-inline class=”mw-default-size”></figure-inline>

API: Asian/Pacific Islander; AI/AN: American Indian/ Alaska Native

• The incidence of bladder cancer is higher in Western countries as compared to developing countries.^[10]

• Transitional cell carcinoma accounts for the majority of bladder cancer in the developed world.^[11]

• Squamous cell carcinoma accounts for a large number of bladder cancer cases in African countries endemic for schistosomiasis, such as Egypt, Uganda, Senegal, Sudan, and Kenya.^[12][13]

• Among patients with bladder cancer in Egypt, squamous cell carcinoma is present in approximately 60% of the cases.^[11]

• In the late 1980’s and early 1990’s, approximately one third of cancer cases in Egypt were cases of bladder cancer. Given the improved treatment of schistosomiasis in Egypt, the incidence of bladder cancer has been decreasing.^[14]

Common risk factors in the development of bladder cancer are smoking, occupational exposure to chemicals, chronic bladder irritation, chemotherapy, radiation therapy, arsenic, personal history of cancer in the urinary tract, congenital bladder anomalies, and aristolochic acids.

• Common risk factors in the development of bladder cancer include:^{[1][2][3][4][5][6]}
  • Smoking
  • Occupational exposure to chemicals
    • Textiles
    • Rubber
    • Paint
    • Leather
    • Dye
    • Print
    • Metal
    • Machining
    • Plastics
    • Arsenic
    • Aristolochic acids
  • Chronic bladder irritation
  • Chronic urinary tract infection
  • Bladder stones
  • Schistosoma haematobium
  • Trauma
  • Chemotherapy
    • Cyclophosphamide
    • Ifosfamide
  • Radiation therapy
  • Personal history of cancer in the urinary tract
  • Congenital bladder anomalies
    • Urachus
    • Exstrophy

• Less common risk factors in the development of bladder cancer include:^{[7][8][9][10]}
  • Chlorine by-products
  • Genetics
    • HRAS mutation
    • Rb1 mutation
    • PTEN/MMAC1 mutation
    • NAT2 slow acetylator phenotype
    • GSTM1 null phenotype
  • Overuse of analgesics
  • Outdoor air pollution

There is insufficient evidence to recommend routine screening for bladder cancer.

There is insufficient evidence to recommend routine screening for bladder cancer.

Common complications of bladder cancer include metastasis, anemia, hydronephrosis, urethral stricture, and urinary incontinence. Prognosis is generally good, and the 5-year survival rate is approximately 77.4%. The prognosis varies with the stages of tumor; carcinoma in situ have the most favorable prognosis.

• The symptoms of bladder cancer usually develop in the 6th and 7th decade of life, and start with symptoms such as hematuria, difficulty urinating and dysuria.^[1][2]

• Common complications of bladder cancer include:^[3][4][5][6]

• Metastasis
• Anemia
• Hydronephrosis
• Urethral stricture
• Urinary incontinence
• Urinary retention
• Ureteral obstruction

• Based on data from 2005-2011, the 5-year survival rate of patients with bladder cancer is approximately 77.4%.^[7]

• Between 2004 and 2010, the 5-year relative survival of patients with bladder cancer was 79.1%.^[8]

• When stratified by age, the 5-year relative survival of patients with bladder cancer was 83.8% and 74.1% for patients <65 and ≥ 65 years of age respectively.^[8]

• The survival of patients with bladder cancer varies with the stage of the disease. Shown below is a table depicting the 5-year relative survival by the stage of bladder cancer:^[8]

• Shown below is an image depicting the 5-year conditional relative survival (probability of surviving in the next 5-years given the cohort has already survived 0, 1, 3 years) between 2004 and 2010 of bladder cancer by stage at diagnosis according to SEER. These graphs are adapted from SEER: The Surveillance, Epidemiology, and End Results Program of the National Cancer Institute.^[8]

Steven C. Campbell, M.D., Ph.D.

The treatment of bladder cancer depends on how deep the tumor invades into the bladder wall. Superficial tumors (those not entering the muscle layer) can be “shaved off” using an electrocautery device attached to a cystoscope. Immunotherapy in the form ofBCG instillation is also used to treat and prevent the recurrence of superficial tumors.^[1] BCG immunotherapy is effective in up to 2/3 of the cases at this stage. Instillations of chemotherapy into the bladder can also be used to treat superficial disease.

Untreated, superficial tumors may gradually begin to infiltrate the muscular wall of the bladder. Tumors that infiltrate the bladder require more radical surgery where part or all of the bladder is removed (a cystectomy) and the urinary stream is diverted. In some cases, skilled surgeons can create a substitute bladder (a neobladder) from a segment of intestinal tissue, but this largely depends upon patient preference, age of patient, renal function, and the site of the disease.

A combination of radiation and chemotherapy can also be used to treat invasive disease. It has not yet been determined how the effectiveness of this form of treatment compares to that of radical ablative surgery.

There is weak observational evidence from one very small study (84) to suggest that the concurrent use of statins is associated with failure of BCG immunotherapy.^[2]

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