What Causes Bladder Cancer
Bladder cancer occurs when cells within the lining of the bladder wall begin to grow in a disordered, uncontrolled way.
Exactly what prompts this disordered growth is not fully known. However, several factors associated with a higher risk of bladder cancer have been identified, including:
- Age – most people diagnosed with bladder cancer are older than 55 years.
- Sex – compared to women, men are 4 times more likely to develop bladder cancer.
- Smoking – smoking is associated with around half of all bladder cancers in men and women.
- Race – in the United States, White Americans have the highest rate of bladder cancer.
- Previous bladder cancer – people who have had bladder cancer may have a recurrence.
- Workplace exposures – certain chemicals in some workplaces may contribute to higher rates of bladder cancer in workers. For example, painters, hairdressers, and truck drivers are at increased risk.
- Arsenic in drinking water.
- Certain types of medication.
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Cxbladder is a cutting-edge genomic urine test that quickly and accurately detects or rules out bladder cancer. The test combines clinical risk factor markers with genetic information, measuring five biomarker genes to detect the presence or absence of bladder cancer in hematuria patients and those being monitored for recurrence.
Cxbladder comes as a suite of tests, each optimised for a different point in the patient journey:
- Cxbladder Triage: Incorporates known bladder cancer risk factors to help quickly rule out the disease.
- Cxbladder Detect: Designed to work alongside other tests to improve overall detection accuracy.
- Cxbladder Monitor: A non-invasive surveillance alternative that can reduce the need for frequent cystoscopies.
Cxbladder gives you peace of mind and will help your physician make informed treatment decisions.
Speak to your doctor or urologist to learn more about Cxbladder and which test might be right for you. You can also contact our Customer Service Team directly.Learn more about Cxbladder Contact us for more information
What Are The Layers Of The Bladder
The bladder consists of three layers of tissue. The innermost layer of the bladder, which comes in contact with the urine stored inside the bladder, is called the mucosa and consists of several layers of specialized cells called transitional cells, which are almost exclusively found in the urinary system of the body. These same cells also form the inner lining of the ureters, kidneys, and a part of the urethra. These cells form a waterproof lining within these organs to prevent the urine from going into the deeper tissue layers. These cells are also termed urothelial cells, and the mucosa is termed the urothelium.
The middle layer is a thin lining known as the lamina propria and forms the boundary between the inner mucosa and the outer muscular layer. This layer has a network of blood vessels and nerves and is an important landmark in terms of the staging of bladder cancer .
The outer layer of the bladder comprises of the detrusor muscle. This is the thickest layer of the bladder wall. Its main function is to relax slowly as the bladder fills up to provide low-pressure urine storage and then to contract to compress the bladder and expel the urine out during the act of passing urine. Outside these three layers is a variable amount of fat that lines and protects the bladder like a soft cushion and separates it from the surrounding organs such as the rectum and the muscles and bones of the pelvis.
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Treatment Options For Advanced Stage Bladder Cancer
If you are diagnosed with stage IV bladder cancer, your healthcare team will discuss the treatment options that are available to you.3 The available options generally depend on if the cancer has spread to other parts of the body.
Treatments for stage IV bladder cancer that has not metastasized, or spread to other parts of the body, may include chemotherapy treatment, or external radiation therapy with or without chemotherapy treatment. Some patients may have a surgery called a radical cystectomy to remove the entire bladder, which may or may not be followed by chemotherapy. If you have a radical cystectomy, the surgeon will likely create another way for urine to be stored and removed from the body.
Treatment for stage IV bladder cancer that has spread to other parts of the body may include treatment with one or more of the following: chemotherapy, immunotherapy, surgery, or external radiation therapy. Some patients may choose to participate in a clinical trial to investigate new types of treatment for bladder cancer.
Chemotherapy For Metastatic Disease
Historically, MVAC had been considered the standard therapy for treating advanced bladder-cancer patients. The efficacy of MVAC was first reported in 1989 when Sternberg and colleagues treated 121 patients with advanced urothelial tract cancers and demonstrated a 72% response rate.232 MVAC was subsequently compared with single-agent cisplatin and shown to be superior in terms of response rate and overall survival in patients with advanced bladder cancer.233 MVAC has also been compared with the previously used multiagent regimen CISCA: 110 patients were randomized to either MVAC or CISCA. MVAC was found to have both a higher objective response rate and a longer median survival.234 Despite superior outcome with MVAC, significant limitations include its severe toxicity . In addition, despite high objective response rates, only a very small percentage of patients with metastatic bladder cancer have long-term disease-free survival .233
Taxanes have significant activity in advanced transitional carcinoma. Paclitaxel has been tested in combination with gemcitabine and cisplatin and demonstrated significant activity in phase II testing.236 Phase III evaluation of the triplet regimen compared with GC alone has been reported in abstract form, and suggests that there is no significant improvement with the addition of a third agent to GC chemotherapy.237
Andrew V. Schally, … Norman L. Block, in, 2013
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What Are The Symptoms Of Stage 4 Bladder Cancer
The most common and most noticeable symptom of bladder cancer is bloody. According to the American Cancer Society, other symptoms of bladder cancer include
- Frequent urination
- A feeling of burning or pain while urinating
- Urinary urgency, even after emptying your bladder
- Difficulty starting or maintaining a strong urine stream
- Frequent trips to the bathroom during the night
It is worth noting that these symptoms can resemble a urinary tract infection. Regardless of the cause these indicators should be quickly evaluated by a medical professional so that treatment can begin for whatever condition should be the cause.
As bladder cancer progresses, though, so do the symptoms. With the progression of cancer, come more severe symptoms such as the inability to pass urine, bone pain, weight loss, pain in the back , swelling in the feet, and generalized weakness.
Risk Factors For Bladder Cancer
There are some things that can make you more likely to develop bladder cancer. These are called risk factors and they include:
- smoking chemicals in cigarettes can cause bladder cancer, so if you smoke, your risk is up to 3 times that of a non-smoker
- age most people with bladder cancer are over 60 years of age
- being male men are around 3 times more likely than women to develop bladder cancer
- chemicals being in contact with certain chemicals for a long period of time, like aromatic amines, benzene products and aniline dyes, which have been linked to bladder cancer
- chronic infections frequent infections of the bladder over a long period of time
- previous cancer treatments some types of radiation therapy around the pelvis, and the chemotherapy drug cyclophosphamide
- family history a first degree relative with bladder cancer increases risk up to nearly 2 times higher than the general population.
Having these risk factors doesnt mean you will develop bladder cancer. Often there is no clear reason for getting bladder cancer. If you are worried about your risk factors, ask your doctor for advice.
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Bladder Cancer Survival Rate
Cancer survival rates are usually discussed in terms of 5-year relative survival, which refers to the proportion of patients still alive five years after diagnosis. Keep in mind that statistics like these are based on large groups of people and cannot predict what might happen with an individual patient.
Roswell Park continually monitors, measures and evaluates all our patient outcomes and survival, and we compare our data to national data collected by the Surveillance, Epidemiology, and End Results Program
AJCC Stage Group Bladder Cancer
Stage at diagnosis for CY 2014-2015
This pie chart illustrates the cancer stage at time of diagnosis of patients with bladder cancer at Roswell Park.1
Five-Year Relative Survival, Bladder Cancer, Stages I-IV
Cases Diagnosed 2006-2013
This graph illustrates the survival rate of patients with bladder cancer at Roswell Park, compared to the survival rates nationwide. Roswell Park patients, at every stage of disease, have better survival rates.2
Relative Survival compares the actual observed survival with the expected survival of persons unaffected by cancer.
Mechanistic Interactions Between Bladder Cancer And Aging
Several broad hypotheses have proposed potential mechanisms for the association between cancer and aging, whereby the biological processes of aging could influence the development and/or progression of cancer in older adults. The processes interact at multiple levels for example, tumor protein 53 a tumor suppressoris involved in both cancer and aging: alteration of the p53 gene is the most frequently encountered mutation in human cancers , and the efficiency of the response to p53 has been found to vary according to age. In a mouse study, Feng et al.28 reported that the efficiency of the p53 response was significantly reduced in older mice compared with their younger counterparts. The reduced response predominantly resulted from decreased transcriptional activity and p53-dependent apoptosis decreased stabilization of p53 after stress was found to be the major factor in this decline.
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Stages Of Bladder Cancer
Staging describes or classifies a cancer based on how much cancer there is in the body and where it is when first diagnosed. This is often called the extent of cancer. Information from tests is used to find out the size of the tumour, which parts of the organ have cancer, whether the cancer has spread from where it first started and where the cancer has spread. Your healthcare team uses the stage to plan treatment and estimate the outcome .
The most common staging system for bladder cancer is the TNM system. For bladder cancer there are 5 stages stage 0 followed by stages 1 to 4. Often the stages 1 to 4 are written as the Roman numerals I, II, III and IV. Generally, the higher the stage number, the more the cancer has spread. Talk to your doctor if you have questions about staging.
When describing the stage, doctors may use the words local, regional or distant. Local means that the cancer is only in the bladder and has not spread to other parts of the body. Regional means close to the bladder or around it. Distant means in a part of the body farther from the bladder.
Find out more about cancer.
After Bladder Cancer Has Been Diagnosed Tests Are Done To Find Out If Cancer Cells Have Spread Within The Bladder Or To Other Parts Of The Body
The process used to find out if cancer has spread within thebladder lining and muscle or to other parts of the body is called staging. The information gathered from the staging process determines the stage of the disease. It is important to know the stage in order to plan treatment. The following tests and procedures may be used in the staging process:
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What Is Muscle Invasive Bladder Cancer
Muscle invasive bladder cancer is a cancer that spreads into the detrusor muscle of the bladder. The detrusor muscle is the thick muscle deep in the bladder wall. This cancer is more likely to spread to other parts of the body.
In the U.S., bladder cancer is the third most common cancer in men. Each year, there are more than 83,000 new cases diagnosed in men and women. About 25% of bladder cancers are MIBC. Bladder cancer is more common as a person grows older. It is found most often in the age group of 75-84. Caucasians are more likely to get bladder cancer than any other ethnicity. But there are more African-Americans who do not survive the disease.
What is Cancer?
Cancer is when your body cells grow out of control. When this happens, the body cannot work the way it should. Most cancers form a lump called a tumor or a growth. Some cancers grow and spread fast. Others grow more slowly. Not all lumps are cancers. Cancerous lumps are sometimes called malignant tumors.
What is Bladder Cancer?
When cells of the bladder grow abnormally, they can become bladder cancer. A person with bladder cancer will have one or more tumors in his/her bladder.
How Does Bladder Cancer Develop and Spread?
The bladder wall has many layers, made up of different types of cells. Most bladder cancers start in the urothelium or transitional epithelium. This is the inside lining of the bladder. Transitional cell carcinoma is cancer that forms in the cells of the urothelium.
Causes And Risk Factors
Researchers dont know exactly what causes bladder cancer, but they do know what increases the risk of getting it. These risk factors range from family history to certain types of medication.
Data published in 2021 on MedRxiv by researchers from the online pharmacy Valisure and Memorial Sloan Kettering Cancer Center showed patients who took Zantac had elevated diagnosis rates of bladder, breast, prostate and thyroid cancer.
Patients should keep in mind that this data suggests a link between ranitidine and increased risk, but it doesnt prove that all people who take ranitidine will get bladder cancer.
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Tests For Bladder Cancer
Your doctor may do some tests to check for bladder cancer:
- urine tests your urine will be checked for signs of bladder cancer
- blood tests to check your general health
- ultrasound a scan on the outside of your abdomen to check for cancer
- cystoscopy the doctor puts a small camera into your bladder to see inside
- biopsy the doctor takes a small sample of the cells from the bladder to check for signs of cancer.
Your doctor might ask you to have further tests. These can include:
- CT scan and x-rays scans that take pictures of the inside of the body, sometimes also called a CT-IVP or a triple phase abdominal-pelvic CT scan
- MRI scan a scan that uses magnetism and radio waves to take pictures of the inside of the body
- bone scan a scan that uses dye to show changes in your bones
- FDG-PET scan a scan that uses an injection of liquid to show cancer cells.
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Future Directions And Research Priorities
Elderly adults with bladder cancer are faced with difficult choices with regard to the optimum management of their condition. Health-care providers need to consider the unique needs of older patients with bladder cancer. When facing any potentially catastrophic illness, issues related to functional independence and quality of life must be considered, as these factors may assume an importance equal to or even greater than that of survival. Many studies fail to include clinical outcome measures that are truly meaningful for older adults therefore, these studies are not able to appreciate the tremendous variability between individuals as they age. As the earlier discussion indicates, aging represents a very large risk factor for the development of bladder cancer, and may also increase the likelihood of muscle-invasive disease. Nevertheless, based on the available evidence, comorbidity, functional status and frailty may represent far better predictors of undesirable outcomes than chronological age alone. With these considerations in mind, future studies of elderly patients will need to incorporate these other dimensions of health status, as is normally done in the context of a geriatric assessment.37 Clinical domains that should be assessed include function, objective measures of physical performance, comorbidity, nutrition, social support, cognition and depression.
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Case : Metastatic Bladder Cancer To Adrenal Gland/liver/lung
A 56-year-old man with bladder cancer was initially treated with radical cystectomy followed by chemotherapy. Follow-up scan including a PET-CT showed an isolated area with high uptake in his left adrenal gland consistent with recurrent metastatic bladder cancer. He was also having side effects from systemic chemotherapy and needed a break. He was referred for consideration of SBRT to his isolated recurrence after surgery and chemotherapy. He was simulated in the supine position in an immobilization device. PET-CT images were co-registered with simulation CT images. Target delineation was performed by the radiation oncologist and the nuclear medicine radiologist. Tumor motion data from 4D-CT dataset were used to plan PTV. SBRT with daily image-guidance approach was taken whereby the metastatic tumor was prescribed 30 Gy in 5 fractions . Rapid fall off was achieved with the treatment plan to for conformal avoidance of small bowels and kidney . Follow-up imaging showed decrease in the adrenal mass.
Ho Kyung Seo, … Sung Han Kim, in, 2018
Genetic Factors In Pathogenesis
Divergent, yet interconnected and overlapping, molecular pathways are likely responsible for the development of noninvasive and invasive bladder tumors. Somatic mutations in fibroblast growth receptor3 and tumor protein p53 in tumor cells appear to be important early molecular events in the noninvasive and invasive pathways, respectively.
FGFR-3, Ras, and PIK3CA mutations occur with high frequency in noninvasive tumors, leading to upregulation of Akt and mitogen-activated protein kinase . Loss of heterozygosity on chromosome 9 is among the most frequent genetic alterations in bladder tumors and is considered an early event.
Large numbers of genomic changes have been detected using karyotyping and comparative genomic hybridization analysis in urothelial carcinoma. Numerically common are losses of 2q, 5q, 8p, 9p, 10q, 18q, and Y. Gains of 1q, 5p, 8q, and 17q are frequently present, and high-level amplifications can be found however, the target genes in the regions of amplifications have not been conclusively identified.
Alterations in the TP53 gene are noted in approximately 60% of invasive bladder cancers. Progression-free survival is significantly shorter in patients with TP53 mutations and is an independent predictor of death among patients with muscle-invasive bladder cancer.
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