Urinary Bladder Cancer
Disease Details
Family Health Simplified
- Description
- Urinary bladder cancer is a malignant growth of cells in the lining of the bladder, often presenting with symptoms such as blood in the urine, pain, and frequent urination.
- Type
- Urinary bladder cancer is typically categorized as a type of carcinoma, with the most common subtype being transitional cell carcinoma (also known as urothelial carcinoma). There is no specific pattern of genetic transmission for the majority of bladder cancer cases, as they are generally considered sporadic. However, certain inherited genetic mutations and family history can increase the risk, indicating a multifactorial and sometimes hereditary component in rare cases.
- Signs And Symptoms
- Bladder cancer characteristically causes blood in the urine, which may be visible or detectable only by microscope. Blood in the urine is the most common symptom in bladder cancer, and is painless. Visible blood in the urine may be of only short duration, and a urine test may be required to confirm non-visible blood. Between 80 and 90% of people with bladder cancer initially presented with visible blood. Blood in the urine may also be caused by other conditions, such as bladder or ureteric stones, infection, kidney disease, kidney cancers or vascular malformations, though these conditions (except kidney cancers) would typically be painful.Other possible symptoms include pain during urination, frequent urination, or feeling the need to urinate without being able to do so. These signs and symptoms are not specific to bladder cancer, and may also be caused by non-cancerous conditions, including prostate infections, overactive bladder or cystitis. Some rare forms of bladder cancer like urachal adenocarcinoma produce mucin, which is then excreted in the urine causing it to be thick.People with advanced disease may have pelvic or bony pain, lower-extremity swelling, or flank pain. Rarely, a palpable mass can be detected on physical examination.
- Prognosis
- People with non-muscle invasive tumors have a favorable outcome (5-year survival is 95% vs. 69% of muscle invasive bladder cancer). However, 70% of them will have a recurrence after initial treatment with 30% of them presenting with muscle invasive disease. Recurrence and progression to a higher disease stage have a less favorable outcome.Survival after radical cystectomy and pelvic lymph node dissection is dependent on the pathological stage. If the disease has not spread to the lymph node and is limited to the bladder (T1 or T2, N0) the 5-year survival is 78%. If it has spread locally around the region of the bladder with no lymph node involved (T3, N0) then the 5-year survival drops to 47%. In disease with lymph node spread (N+, irrespective of T stage) the 5-year survival is 31%. Locally advanced and metastatic disease drastically decreases survival, with a median survival of 3–6 months without chemotherapy. Cisplatin-based chemotherapy has increased the median survival to 15-months. However, the 5-year survival is still 15%.There are several prognostic factors which determine cancer specific survival after radical cystectomy. Factor with detrimental effect of cancer specific survival are old age, higher tumor grade and pathological stage, lymph node metastasis, presence of lymphovascular invasion and positive soft tissue margin. Lymph node density (positive lymph nodes/total lymph nodes observed in the specimen from surgery) is a predictor of survival in lymph node positive disease. Higher the density lower is the survival.
- Onset
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Urinary bladder cancer typically presents with the following aspects regarding onset:
- **Age of Onset**: Most commonly diagnosed in individuals aged 65 and older, though it can occur at a younger age.
- **Risk Factors**: Smoking, exposure to certain industrial chemicals, chronic bladder inflammation, and a history of previous cancer treatments.
"nan" isn't a recognized factor or term relevant to the onset description of urinary bladder cancer. - Prevalence
- Prevalence of urinary bladder cancer varies by region, age, and sex. Globally, it is the 10th most common cancer. It is more prevalent in older adults, particularly those aged 65 and above, and is more common in men than in women. The risk is higher in developed countries compared to developing nations.
- Epidemiology
- Globally, in 2017, bladder cancer resulted in 196,000 deaths, a 5.4% (age adjusted) decrease from 2007. In 2018, the age adjusted rates of new cases of bladder cancer was 6 cases per 100,000 people and age adjusted death rate was 2 deaths per 100,000 people. Lebanon and Greece have the highest rate of new cases. In Lebanon, this high risk is attributed to high number of smokers and petrochemical air pollution.The risk of bladder cancer occurrence is four times higher in men than in women. Smoking can only partially explain this higher rates in men in western hemisphere. One other reason is that the androgen receptor, which is much more active in men than in women, may play a part in the development of the cancer. This hypothesis is also supported by the fact that men undergoing androgen suppression therapy for unrelated reason seem to have a lower risk of developing bladder cancer. In Africa, men are more prone to do field work and are exposed to infection with Schistosoma, this may explain to a certain extent the gap in incidence of squamous cell cancers in areas where bladder cancer is endemic. However, women present with more aggressive disease and have worse outcomes than men. This difference in outcomes is attributed to numerous factors such as, difference in carcinogen exposure, genetics, social and quality of care. One of the common signs of bladder cancer is hematuria and is quite often misdiagnosed as urinary tract infection in women, leading to a delay in diagnosis. Moreover, as mentioned earlier PSCA gene may play a role in aggressive tumors in women.
- Intractability
- Urinary bladder cancer is not universally intractable. Its treatment and prognosis depend on factors such as the stage and grade of the cancer, the patient's overall health, and how well the cancer responds to treatment. Early-stage bladder cancer can often be treated successfully with methods like surgery, intravesical therapy, or radiation. Advanced stages may require more aggressive treatments, including systemic chemotherapy or immunotherapy. While some cases can be difficult to treat and may recur, many patients achieve remission with appropriate medical interventions.
- Disease Severity
- Urinary bladder cancer severity can vary widely depending on several factors, such as the stage and grade of the cancer, as well as the patient's overall health. It can range from low-grade, non-invasive tumors that are relatively easy to treat, to high-grade, invasive cancers that are more aggressive and harder to manage. Early detection significantly improves the prognosis and treatment outcomes. Advanced stages may require more complex treatments such as surgery, chemotherapy, and radiation therapy.
- Healthcare Professionals
- Disease Ontology ID - DOID:11054
- Pathophysiology
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The pathophysiology of urinary bladder cancer involves abnormal and uncontrolled growth of cells within the bladder lining, often resulting from genetic mutations and environmental risk factors. Key contributors include:
1. **Genetic Mutations:** Alterations in genes like TP53, FGFR3, and RAS can lead to abnormal cell proliferation.
2. **Environmental Factors:** Exposure to carcinogens such as those found in tobacco smoke, occupational chemicals (like aromatic amines), and arsenic in drinking water.
3. **Chronic Irritation:** Conditions like chronic urinary infections and bladder stones can contribute to cellular changes and cancer development.
4. **Inflammation:** Long-term inflammation can trigger oxidative stress, promoting DNA damage and malignancy.
Cancer development typically progresses from superficial, non-muscle-invasive tumors to more advanced stages, potentially invading the bladder muscle and surrounding tissues if untreated. - Carrier Status
- The concept of "carrier status" is typically relevant for genetic diseases where an individual carries one copy of a mutated gene but does not show symptoms. Urinary bladder cancer is primarily considered a sporadic disease rather than a hereditary one. It is not accurately described in terms of "carrier status" because it is not passed from parent to offspring in a simple inheritance pattern. However, certain genetic mutations and hereditary syndromes, such as Lynch syndrome, can increase the risk of urinary bladder cancer. Environmental factors, such as smoking and exposure to certain chemicals, also significantly contribute to its development.
- Mechanism
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Urinary bladder cancer, primarily urothelial carcinoma, involves several mechanisms and molecular pathways:
1. **Genetic Mutations**: Mutations in genes such as FGFR3, TP53, and RB1 are commonly implicated. FGFR3 mutations are associated with low-grade, non-invasive tumors, while TP53 and RB1 mutations are linked to high-grade, invasive cancers.
2. **Epigenetic Alterations**: Changes in DNA methylation and histone modification can lead to altered gene expression, contributing to cancer development and progression.
3. **Cell Cycle Dysregulation**: Abnormal regulation of the cell cycle due to mutations in cell cycle regulatory genes leads to uncontrolled cell proliferation.
4. **Signal Transduction Pathways**: Alterations in pathways like PI3K/AKT/mTOR, Ras/MAPK, and Hedgehog signaling are involved in promoting cell growth, survival, and metastasis.
5. **Inflammation and Immune Evasion**: Chronic inflammation and immune evasion play critical roles, with tumor cells developing mechanisms to escape immune surveillance.
6. **Chromosomal Alterations**: Aneuploidy and chromosomal rearrangements contribute to genomic instability and tumor heterogeneity.
7. **Microenvironment**: The tumor microenvironment, including interactions with stromal and immune cells, influences tumor growth and metastasis through various signaling mechanisms.
These mechanisms work collectively, contributing to the initiation, progression, and resistance to therapy in urinary bladder cancer. - Treatment
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The treatment of bladder cancer depends on how deeply the tumor invades into the bladder wall.Treatment strategies for bladder cancer include:
Non-muscle invasive: transurethral resection of bladder tumor (TURBT) with or without intravesical chemotherapy or immunotherapy
Muscle invasive
Stage II/Stage IIIA: radical cystectomy plus neoadjuvant chemotherapy (multimodal therapy, preferred) or transurethral resection with chemoradiation (trimodal therapy, highly selected people) or partial cystectomy plus neoadjuvant chemotherapy (in highly selected people)
Stage IIIB/IVA: cisplatin-based chemotherapy followed by radical cystectomy or chemoradiation or observation depending on treatment response
Stage IVB (locally advanced; unresectable tumors): palliative radiotherapy
Metastatic disease: cisplatin-based chemotherapy
Metastatic disease but unfit for cisplatin-based chemotherapy: carboplatin-based chemotherapy
Metastatic disease with contraindication for chemotherapy: checkpoint inhibitors if programmed death ligand 1 (PD L1) positive
Squamous cell carcinoma or adenocarcinoma of bladder: radical cystectomy - Compassionate Use Treatment
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For urinary bladder cancer, compassionate use treatment and off-label or experimental treatments may include:
1. **Checkpoint Inhibitors:** Drugs like pembrolizumab (Keytruda) and atezolizumab (Tecentriq) which are FDA-approved but also being explored for additional uses beyond their initial indications.
2. **FGFR Inhibitors:** Erdafitinib (Balversa) is approved for specific genetic mutations in advanced bladder cancer but still being studied in broader contexts.
3. **Antibody-Drug Conjugates:** Enfortumab vedotin-ejfv (Padcev) is approved but is also being explored in various combinations and settings.
4. **Photodynamic Therapy (PDT):** Still considered experimental, it involves using light-sensitive drugs and laser light to destroy cancer cells.
5. **Gene Therapy:** Research continues into using gene therapy to treat bladder cancer, though it remains experimental at this stage.
6. **Bladder-Sparing Protocols:** Experimental regimens often combine radiation and chemotherapy to avoid removing the bladder.
7. **Immunotherapy Combinations:** Trials are ongoing for combining checkpoint inhibitors with other treatments like chemotherapy or radiation to improve outcomes.
These treatments are part of ongoing research and may be available through clinical trials or specific compassionate use programs for patients with advanced disease resistant to standard therapies. Always consult with a healthcare provider for the most appropriate and up-to-date options. - Lifestyle Recommendations
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For urinary bladder cancer, some lifestyle recommendations that may help reduce the risk or support treatment include:
1. Smoking Cessation: If you smoke, quitting is the most important step you can take. Smoking is a major risk factor for bladder cancer.
2. Hydration: Drink plenty of fluids, particularly water, to help flush toxins from your bladder.
3. Diet: Eat a balanced diet rich in fruits, vegetables, and whole grains. These foods contain antioxidants and nutrients that support overall health.
4. Physical Activity: Engage in regular physical activity to maintain a healthy weight and overall well-being.
5. Occupational Safety: If you work with chemicals or in an environment with potential carcinogens, follow safety protocols to minimize exposure.
6. Regular Check-Ups: Attend regular medical check-ups, especially if you have risk factors such as a family history of bladder cancer.
These recommendations can help manage bladder health, though they do not replace professional medical advice or treatment. - Medication
- For urinary bladder cancer, medications include chemotherapy drugs like cisplatin, gemcitabine, and carboplatin, immune checkpoint inhibitors such as pembrolizumab and atezolizumab, and Bacillus Calmette-Guérin (BCG) for intravesical therapy. The choice of medication depends on the stage and type of bladder cancer, as well as the patient's overall health.
- Repurposable Drugs
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Repurposable drugs for urinary bladder cancer include:
1. **Metformin**: Primarily used for diabetes, it has shown potential anti-cancer properties by inhibiting cancer cell growth.
2. **Statins**: These cholesterol-lowering drugs may have anti-tumor effects.
3. **Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)**: Drugs like aspirin and celecoxib have been studied for their potential to reduce cancer risk or progression.
4. **Thiazolidinediones**: These diabetes drugs have shown potential in affecting cancer cell signaling and growth.
5. **Beta-blockers**: Commonly used for heart conditions, they might inhibit cancer progression through effects on stress hormones.
It's important to note that while these drugs show potential, their use in bladder cancer should be under strict medical supervision and usually within clinical trials or additional studies. - Metabolites
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For urinary bladder cancer, common metabolites that may be studied include:
1. **N-acetylated aromatic amines**: These are metabolites from tobacco smoke and certain industrial chemicals, and their presence is linked to an increased risk of bladder cancer.
2. **Phenylacetylglutamine (PAG)**: Higher levels in urine have been associated with cancer patients.
3. **Tryptophan and its metabolites**: Altered levels can be observed.
4. **Amino acids and their derivatives**: Changes in their urinary excretion pattern may occur.
These metabolites can assist in understanding the disease's pathology and potential biomarkers for diagnosis and monitoring. - Nutraceuticals
- Research into nutraceuticals as a potential therapy for urinary bladder cancer is ongoing, but there is no strong evidence to support their use as a primary treatment. Nutraceuticals might serve as complementary treatments, aiming to support overall health and potentially enhance the effects of conventional therapies. Common compounds studied include antioxidants, vitamins, and certain plant extracts. Always consult with a healthcare professional before using any nutraceuticals in cancer treatment.
- Peptides
- Peptides have been explored in the context of urinary bladder cancer for various purposes, such as diagnostics, therapeutics, and imaging. Specifically, peptide-based therapies can target cancer cells with high specificity, potentially reducing toxicity to normal tissues. In diagnostics, peptides can be used to develop biomarkers for early detection. Nanotechnology can enhance the delivery and effectiveness of peptide-based therapies. Nanoparticles can protect peptides from degradation, improve their stability, and ensure controlled release at the tumor site, thereby improving therapeutic outcomes.