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Bladder Cancer

Updated : February 8, 2024





Background

The World Health Organization has substituted transitional cell cancer terminology with urothelial carcinoma. Urothelial carcinoma is the most typical prevalent histologic form of bladder cancer, accounting for nearly 90% of all cases. The invasion of neoplastic cells of urothelial origin into the lamina propria, basement membrane, or deeper is defined as Urothelial Cancer.

When the thickness of invasion is 2 mm or less, it is termed micro invasion. The World Health Organization categorizes bladder cancers as low-grade grade 1 and 2 or high-grade grade 3. The difference between low- and high-grade urothelial cancer has consequences for risk classification and patient treatment.

Epidemiology

Bladder Carcinoma is the sixth most frequent cancer in the world. It is the fourth most frequent cancer in men and the eighth most prevalent cancer in women in the United States. Bladder Cancer is twice as frequent among Caucasians than in African Americans, and the disease’s prevalence increases with age.

In the United States, most bladder carcinoma is urothelial carcinoma, with fewer than 5% being adenocarcinoma or squamous cell carcinoma. In underdeveloped nations, the prevalence of bladder cancer is double that of developed countries. Most bladder carcinoma in underdeveloped nations is squamous cell carcinomas associated with endemic schistosomiasis.

Anatomy

Pathophysiology

Urothelial cancer develops along two paths, the first involving papillary lesions and the second involving flat lesions. Copy number changes and genomic instability are associated with tumor growth and a worse prognosis. Low-grade papillary cancers are characterized by chromosome 9 loss of heterozygosity and activating mutations of fibroblast growth factor receptor 3, telomerase reverse transcriptase, phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform, and inactivating mutations of STAG2.

As a result of CDKN2A loss, low-grade papillary non-muscle-invasive bladder cancer can develop into muscle-invasive bladder cancer. Muscle-invasive bladder cancer develops from flattened dysplasia or cancer in situ, and the lesions have TP53 mutations and chromosome 9 LOH. The aggressive carcinoma can then lose RB1 and PTEN, among other changes, gaining metastatic potential.

Non-muscle-invasive bladder cancer often has diploid or near-diploid karyotypes and fewer copies of number changes than muscle-invasive bladder cancer. Muscle-invasive bladder cancer is frequently aneuploid, with multiple chromosomal changes.

Etiology

There are several established risk factors for bladder cancer. Smoking, schistosomiasis infection, and exposure to specific chemicals are also significant risk factors. The primary risk factor for bladder cancer is smoking. The risk of bladder cancer in smokers is two to six times that of nonsmokers; the risk varies according to smoking period and intensity.

Schistosomiasis infection is a major cause of bladder cancer in underdeveloped nations. The eggs of Schistosoma haematobium embed in the bladder wall, causing irritation, persistent inflammation, squamous metaplasia, and dysplasia, eventually progressing to squamous cell carcinoma of the urinary bladder.

Bladder cancer is linked to industrial exposure to paint, rubber, petroleum compounds, and dyes. Arylamine dye, aniline dye, phenacetin, cyclophosphamide, and arsenic are all chemicals linked to bladder cancer.

Genetics

Prognostic Factors

Several variables determine the outcome of urothelial cancer. The most important prognostic factor for urinary bladder cancer is the TNM stage. The 5-year overall survival rate for pT1 is 75%, 50% for pT2, and 20% for pT3. The invasion of the muscularis propria determines if a patient is classified as pT1 or pT2.

Compared to conventional urothelial cancer, some histologic variations of urothelial cancer have a worse prognosis. Urothelial carcinoma with rhabdoid characteristics, plasmacytoid carcinoma, urothelial micro-papillary carcinoma, sarcomatoid carcinoma, undifferentiated carcinoma, and small cell carcinoma are among these forms.

Lymphovascular invasion, the development of urothelial carcinoma in situ, recurrence, tumor size, and multicentricity are other poor prognostic markers for urothelial cancer.

Clinical History

Physical Examination

Age group

Associated comorbidity

Associated activity

Acuity of presentation

Differential Diagnoses

Laboratory Studies

Imaging Studies

Procedures

Histologic Findings

Staging

Treatment Paradigm

by Stage

by Modality

Chemotherapy

Radiation Therapy

Surgical Interventions

Hormone Therapy

Immunotherapy

Hyperthermia

Photodynamic Therapy

Stem Cell Transplant

Targeted Therapy

Palliative Care

Medication

 

thiotepa

30 - 60

mg

by intravesical instillation done into the bladder once, and retained for 2hrs, if the patient cannot maintain 60 ml for 2hrs, and given in a volume of 30 ml The therapy is recommended once a week for four weeks, and the treatment may be repeated if necessary but given with caution



doxorubicin

30

mg/m^2

Intravenous (IV)

on day 2 in the 14-day course in combination with methotrexate, cisplatin, and growth factor supporter.
MAVC regimen: 30 mg/m2 IV on day 2 in the 28-course in combination with methotrexate, vinblastine, and cisplatin for up to 6 cycles.



pemetrexed

21-day cycle for metastatic bladder & cervical cancer:

500

mg

Intravenous (IV)

on the first day of the cycle, repeat the cycle until disease progression



nadofaragene firadenovec 

Once every three months, instill 75 mL of 3 x 1011 viral particles (vp)/mL into the bladder.



oportuzumab monatox (Pending FDA Approval) 

FDA approval is pending as intravesical administration for high-risk bladder cancer



cisplatin 

Cisplatin is used in the treatment of advanced bladder cancer with a recommended dose of 50 to 70 mg/m2 via IV administration with a duration of 3 or 4 weeks based on radiation therapy or chemotherapy previously administered
In the case of patients who are pretreated, the heavily recommended starting dose is 50 mg/m2/cycle, which is repeated every four weeks duration



Dose Adjustments

Renal Dose Adjustment
In case of renal impairment, the dose is decreased by 25% if CrCl is between 10 and 50 mL/min. If CrCl is above 10 mL/min, then administer a dose that is 50 % of the initial dose

apaziquone hydroquinone 

Administer a dose of 4 mg via intravesical route (by using urethral catheter into the bladder) for 6 times every week



 
 

thiotepa

The dose selection for patients above 65 years old needs to be cautious, as their renal and hepatic function is weaker      Hence starting with the lower dose is recommended



Media Gallary

References

https://www.ncbi.nlm.nih.gov/books/NBK536923

Bladder Cancer

Updated : February 8, 2024




The World Health Organization has substituted transitional cell cancer terminology with urothelial carcinoma. Urothelial carcinoma is the most typical prevalent histologic form of bladder cancer, accounting for nearly 90% of all cases. The invasion of neoplastic cells of urothelial origin into the lamina propria, basement membrane, or deeper is defined as Urothelial Cancer.

When the thickness of invasion is 2 mm or less, it is termed micro invasion. The World Health Organization categorizes bladder cancers as low-grade grade 1 and 2 or high-grade grade 3. The difference between low- and high-grade urothelial cancer has consequences for risk classification and patient treatment.

Bladder Carcinoma is the sixth most frequent cancer in the world. It is the fourth most frequent cancer in men and the eighth most prevalent cancer in women in the United States. Bladder Cancer is twice as frequent among Caucasians than in African Americans, and the disease’s prevalence increases with age.

In the United States, most bladder carcinoma is urothelial carcinoma, with fewer than 5% being adenocarcinoma or squamous cell carcinoma. In underdeveloped nations, the prevalence of bladder cancer is double that of developed countries. Most bladder carcinoma in underdeveloped nations is squamous cell carcinomas associated with endemic schistosomiasis.

Urothelial cancer develops along two paths, the first involving papillary lesions and the second involving flat lesions. Copy number changes and genomic instability are associated with tumor growth and a worse prognosis. Low-grade papillary cancers are characterized by chromosome 9 loss of heterozygosity and activating mutations of fibroblast growth factor receptor 3, telomerase reverse transcriptase, phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform, and inactivating mutations of STAG2.

As a result of CDKN2A loss, low-grade papillary non-muscle-invasive bladder cancer can develop into muscle-invasive bladder cancer. Muscle-invasive bladder cancer develops from flattened dysplasia or cancer in situ, and the lesions have TP53 mutations and chromosome 9 LOH. The aggressive carcinoma can then lose RB1 and PTEN, among other changes, gaining metastatic potential.

Non-muscle-invasive bladder cancer often has diploid or near-diploid karyotypes and fewer copies of number changes than muscle-invasive bladder cancer. Muscle-invasive bladder cancer is frequently aneuploid, with multiple chromosomal changes.

There are several established risk factors for bladder cancer. Smoking, schistosomiasis infection, and exposure to specific chemicals are also significant risk factors. The primary risk factor for bladder cancer is smoking. The risk of bladder cancer in smokers is two to six times that of nonsmokers; the risk varies according to smoking period and intensity.

Schistosomiasis infection is a major cause of bladder cancer in underdeveloped nations. The eggs of Schistosoma haematobium embed in the bladder wall, causing irritation, persistent inflammation, squamous metaplasia, and dysplasia, eventually progressing to squamous cell carcinoma of the urinary bladder.

Bladder cancer is linked to industrial exposure to paint, rubber, petroleum compounds, and dyes. Arylamine dye, aniline dye, phenacetin, cyclophosphamide, and arsenic are all chemicals linked to bladder cancer.

Several variables determine the outcome of urothelial cancer. The most important prognostic factor for urinary bladder cancer is the TNM stage. The 5-year overall survival rate for pT1 is 75%, 50% for pT2, and 20% for pT3. The invasion of the muscularis propria determines if a patient is classified as pT1 or pT2.

Compared to conventional urothelial cancer, some histologic variations of urothelial cancer have a worse prognosis. Urothelial carcinoma with rhabdoid characteristics, plasmacytoid carcinoma, urothelial micro-papillary carcinoma, sarcomatoid carcinoma, undifferentiated carcinoma, and small cell carcinoma are among these forms.

Lymphovascular invasion, the development of urothelial carcinoma in situ, recurrence, tumor size, and multicentricity are other poor prognostic markers for urothelial cancer.

thiotepa

30 - 60

mg

by intravesical instillation done into the bladder once, and retained for 2hrs, if the patient cannot maintain 60 ml for 2hrs, and given in a volume of 30 ml The therapy is recommended once a week for four weeks, and the treatment may be repeated if necessary but given with caution



doxorubicin

30

mg/m^2

Intravenous (IV)

on day 2 in the 14-day course in combination with methotrexate, cisplatin, and growth factor supporter.
MAVC regimen: 30 mg/m2 IV on day 2 in the 28-course in combination with methotrexate, vinblastine, and cisplatin for up to 6 cycles.



pemetrexed

21-day cycle for metastatic bladder & cervical cancer:

500

mg

Intravenous (IV)

on the first day of the cycle, repeat the cycle until disease progression



nadofaragene firadenovec 

Once every three months, instill 75 mL of 3 x 1011 viral particles (vp)/mL into the bladder.



oportuzumab monatox (Pending FDA Approval) 

FDA approval is pending as intravesical administration for high-risk bladder cancer



cisplatin 

Cisplatin is used in the treatment of advanced bladder cancer with a recommended dose of 50 to 70 mg/m2 via IV administration with a duration of 3 or 4 weeks based on radiation therapy or chemotherapy previously administered
In the case of patients who are pretreated, the heavily recommended starting dose is 50 mg/m2/cycle, which is repeated every four weeks duration



Dose Adjustments

Renal Dose Adjustment
In case of renal impairment, the dose is decreased by 25% if CrCl is between 10 and 50 mL/min. If CrCl is above 10 mL/min, then administer a dose that is 50 % of the initial dose

apaziquone hydroquinone 

Administer a dose of 4 mg via intravesical route (by using urethral catheter into the bladder) for 6 times every week



thiotepa

The dose selection for patients above 65 years old needs to be cautious, as their renal and hepatic function is weaker      Hence starting with the lower dose is recommended



https://www.ncbi.nlm.nih.gov/books/NBK536923