Know the Facts About Bladder Cancer

You likely know that your bladder’s job is to store and release urine, helping to get rid of toxins. But did you know that bladder cancer affects about 73,500 people a year?¹

In this post, we'll share some key facts about bladder cancer一the sixth most common cancer in the United States.² We’ll learn what bladder cancer is, its symptoms, and risk factors. We’ll dive into diagnosis and treatment options, and describe how a personalized test can inform important health care decisions if you or a loved one is living with bladder cancer. And we’ll share some resources for survivorship and caregiving.

What is bladder cancer?

Like other forms of cancer, bladder cancer develops from abnormal cells growing out of control. Certain genetic changes in the cells一most of which occur spontaneously一spur this abnormal growth.³ Over time, these abnormal cells can cluster together to form a cancerous tumor. ¹

Several types of cancer can start in the bladder. Each type involves different types of cells. The most common type is urothelial carcinoma, which accounts for 90% of all bladder cancers.² Urothelial carcinoma starts in the transitional cells that line the inside of the bladder and other parts of the urinary tract. For this reason, it is sometimes also known as transitional cell carcinoma (TCC).

Less common types of bladder cancer include:

• Squamous cell carcinoma

• Adenocarcinoma

• Small cell carcinoma

• Sarcoma

Different types of bladder cancer require different treatments. If you are diagnosed with bladder cancer, your doctor will run tests to learn which type you have.

How are muscle invasive and non-muscle invasive bladder cancer different?

If you have bladder cancer, your doctor also needs to know how far into your bladder wall the cancer has spread. This will allow them to determine if the cancer is muscle invasive or non-muscle invasive.

Non-muscle invasive bladder cancer (NMIBC) only affects cells in the inner layer of the bladder. NMIBC is sometimes called early or superficial bladder cancer. About 70% of all bladder cancers are diagnosed at this stage.⁴

One subtype of NMIBC is in situ bladder cancer. In situ bladder cancer is a flat, high-grade (fast-growing) tumor in the inner layer of bladder cells. In situ bladder cancers have a 40-60% chance of progressing to muscle invasive bladder cancer within 5 years of diagnosis.⁵

Muscle invasive bladder cancer (MIBC) has spread through the inner layer of cells of the bladder wall into a muscle called the detrusor. The detrusor helps push urine out of the bladder during urination.⁶ 20-25% of all bladder cancers are first diagnosed as MIBC.⁷ At this stage, the cancer is more likely to spread, or metastasize, to other organs. NMIBC can become invasive over time if undetected or untreated. 20-25% of NMIBC that are diagnosed as high risk for returning or progressing will eventually become MIBC.⁷

What are risk factors for bladder cancer?

Ongoing research is underway to understand exactly how and why bladder cancer develops. The biggest known risk factor for developing bladder cancer is smoking.² Smoking causes an estimated 50% of all bladder cancers, and can triple your personal risk.⁸

Other major bladder cancer risk factors include:

• Age: About 90% of people with bladder cancer are over the age of 55. The average age at diagnosis is 73. Although less common, younger people can still develop bladder cancer.⁹

• Biological sex: Biological males are more likely to get diagnosed with bladder cancer than biological females.⁸ However, biological females are more likely to be diagnosed at a more advanced stage and have worse survival rates. This pattern may be linked to their symptoms being mistaken for conditions like urinary tract infections.¹⁰

• Race: White people are about twice as likely to develop bladder cancer than African American or Hispanic people, but African American people are twice as likely to die than White people .^{8, 11}

• Family history: Some bladder cancers are linked to changes in genes that can be passed down from generation to generation. Lynch syndrome, for example, is an inherited genetic condition that increases the risk for several types of cancer, including colorectal, uterine (endometrial), and bladder cancer.¹² If certain types of cancers run in your family, you may be at higher risk for bladder cancer.

• Structural changes present at birth: Rarely, babies are born with bladder conditions that increase their lifetime risk of developing bladder cancer.⁸

• Exposure to chemicals: Certain industrial and organic chemicals are known to cause bladder cancer. These chemicals can affect people who work in manufacturing, truck driving, hairdressing, and other fields.⁸

• Not drinking enough fluids: People who drink more water are less likely to get bladder cancer.⁸

• Arsenic in drinking water: High levels of arsenic in water are linked to a higher bladder cancer risk.⁸

How can I lower my risk of bladder cancer?

The best way to reduce your risk of bladder cancer is to avoid smoking. Eating a healthy diet, staying hydrated, and trying to avoid exposure to certain chemicals, when possible, can also help.¹³

However, not all cases of bladder cancer can be prevented. If you are concerned about your risk for bladder cancer, talk to your doctor or genetic counselor about how to reduce it.

What are symptoms of bladder cancer?

In most cases, the first symptom of bladder cancer is blood in urine, or hematuria.¹⁴ Blood in urine can vary in color from orange, to pink, to dark red. It can appear just once, or for a short time before going away. Many times, there is no bladder pain associated with blood in urine. Sometimes, blood in urine cannot be seen with the naked eye and is only detected during a urine test (urinalysis).¹⁴

Blood in urine can be caused by other conditions, including infection, kidney stones, and polycystic kidney disease.¹⁵ If you notice any blood in your urine, see a doctor right away.

Another major symptom, especially in early bladder cancers, is difficulty urinating. This can include an increase in urinary frequency (how often you urinate), burning or pain during urination, and changes in flow. Some of these difficulties can be caused by a urinary tract infection or other conditions. ¹⁴

If bladder cancer is more advanced, other symptoms can include:

• Inability to urinate

• Pain in the lower back (on one side) or pelvis

• Weight loss and decreased appetite

• Fatigue or weakness

• Swelling in feet

• Bone pain

If you experience any of these symptoms, visit your doctor. They can run tests to help determine the cause, and recommend further testing if bladder cancer is suspected.

How is bladder cancer diagnosed?

If your doctor suspects bladder cancer based on your symptoms and/or risk factors, they may refer you to a urologist一a doctor that specializes in the bladder and other parts of the urinary tract. Sometimes, you may see a urologic oncologist (a bladder cancer specialist). In the following sections we will use “doctor” to refer to the provider who is diagnosing and treating you for cancer.

Your doctor may recommend one or more tests to help them make a diagnosis. During your initial workup, your doctor may order:

• Urine tests: These tests are done on a urine sample and look for different signs of bladder cancer. Urine analysis looks for blood, urine cytology looks for cancer cells, urine culture looks for signs of infection, and urine tumor marker tests look for molecules that are associated with cancer.

• Cystoscopy: This procedure involves looking at the inside of your bladder with a tiny camera. The camera is attached to the end of a thin tube that is inserted into the urethra (the tube through which urine exits your body). Cystoscopy can usually be done in the doctor’s office.

• Imaging: A CT or MRI scan can help determine if cancer has spread to other tissues, organs, or lymph nodes.

What is a TURBT?

If a cystoscopy shows an area of the bladder that appears abnormal, your doctor may recommend a transurethral resection of bladder tumor (TURBT). The TURBT is a surgical procedure that provides a better look at the inside of the bladder to help confirm or rule out cancer. If cancer is found, the TURBT can also determine if it is muscle invasive or non-muscle invasive.

The TURBT is generally performed in a hospital under anesthesia. A thin, rigid tool called a resectoscope is inserted into the bladder through the urethra. Your doctor will take a sample, or biopsy, of abnormal cells to examine under a microscope. This will help them understand the type and stage of your cancer, and inform which treatment options are best for you.

TURBT is also considered a treatment for some early bladder cancers because your doctor may be able to remove part of all of the tumor during the procedure. Some people who are receiving TURBT for treatment need to have more than one to increase the amount of tumor tissue that is removed. After a TURBT, you can usually go home the same day or the next day. Side effects are usually mild, and can include bleeding and pain during urination.¹⁶

Your doctor will likely use a combination of tests to diagnose your bladder cancer and understand how to treat it appropriately.

How is bladder cancer treated?

Bladder cancer treatment depends on type, stage, whether it is muscle invasive, and other factors. You and your doctor should discuss your treatment options and their potential side effects, especially if you have other health concerns.

Early-stage bladder cancer treatment

Early-stage bladder cancers are most often treated with TURBT followed by intravesical therapy一a direct injection of chemotherapy, immunotherapy, or targeted therapy into the bladder to kill any remaining cancer cells. Bacillus Calmette-Guerin is a common type of intravesical immunotherapy that activates your own immune system to attack bladder cancer cells. Intravesical therapy can be given just once, or at regular intervals over a period of time.¹⁷

Advanced bladder cancer treatment

More advanced bladder cancers cannot be fully treated with TURBT and/or intravesical therapy. If the cancer has invaded the muscle, your urologist may recommend a partial or radical (full) cystectomy. Cystectomy is the removal of part or all of the bladder. Sometimes nearby tissues and organs are removed as well.

If you have a cystectomy, you may need to have additional reconstructive surgery to give your body a way to store and release urine. This can include creating a new passageway and opening for urine (diversion) or creating a bladder-like structure (neobladder) using tissue from your intestine.¹⁷

Some people who need to get a cystectomy will have chemotherapy and/or radiation first. Chemotherapy given before surgery is called neoadjuvant chemotherapy, and is intended to reduce the chance that cancer will recur after the cystectomy. This type of chemotherapy is systemic (whole body), and can sometimes cause serious side effects like nausea, fatigue, and infection. There are many possible combinations of chemotherapy drugs, and sometimes doctors will recommend combining chemotherapy with radiation (a treatment that kills cells with high-energy radiation).¹⁸

After a cystectomy, some people may need to have additional chemotherapy, radiation, or immunotherapy. This is called adjuvant treatment, and is intended to reduce the chance that the cancer will come back or spread.¹⁸ In 2021, the FDA approved an immunotherapy drug called nivolumab for use after cystectomy for people with urothelial carcinoma whose cancer was at high risk of coming back. For some of these people, nivolumab can improve their outcomes.¹⁹

For all forms of bladder cancer treatment, you and your doctor will weigh the pros and cons to make the best decision for your care.

How likely is bladder cancer to recur after treatment?

Bladder cancer recurrence can occur after treatment, sometimes more than once. The likelihood of recurrence depends on the type of bladder cancer and how advanced it was when diagnosed. Early-stage bladder cancer can often be cured,²⁰ while muscle invasive bladder cancer has a 50% chance of metastasizing to other parts of your body.²¹ Your doctor can monitor your cancer during and after treatment for signs that your cancer is coming back or progressing.

What are the outcomes for people with bladder cancer?

Outcomes for people with bladder cancer depend on many factors, including the stage and type of the cancer, as well as on personal characteristics like age and overall health. In recent years, the rate of new bladder cancers in both sexes has been falling. The rate of deaths has also been falling for biological females but is stable for biological males.⁹

The table below shows the five-year survival rate for different stages of bladder cancer—the percentage of people who will be alive five years after a diagnosis of bladder cancer.

Keep in mind that these rates are based on people diagnosed with bladder cancer between 2012-2018.²² As treatments improve, bladder cancer survival rates may also improve. These rates also do not take into account other factors such as age and overall health.

What is molecular residual disease (MRD) testing for bladder cancer?

Your doctor needs tools to help them make decisions about your bladder cancer treatment. Molecular residual disease (MRD) testing detects and measures small traces of cancer that may be detectable before, during, or after treatment. Doctors can monitor MRD to help guide and tailor your treatment.

One way to detect MRD is to test for circulating tumor DNA (ctDNA)—tiny fragments of a tumor’s DNA that can appear in your bloodstream when cancer is present. Signatera^TM is a personalized test from Natera that detects and evaluates ctDNA.

Signatera works by taking a small tissue sample from your tumor and creating a custom “signature” of your cancer. This signature can be used to detect and evaluate ctDNA in your blood. Blood draws are used to check for ctDNA anytime Signatera is ordered by your doctor.

Bladder cancers, especially muscle invasive bladder cancers, shed circulating tumor DNA into your bloodstream. Clinical studies have shown that using Signatera to monitor ctDNA levels over time can help doctors understand if:

• Bladder cancer is remaining after neoadjuvant chemotherapy or surgery²³

• You may benefit from additional treatment²³

• Your cancer is likely to come back in the future²⁴

• Your cancer is responding to immunotherapy²⁵

To learn more about Signatera, visit https://www.natera.com/oncology/signatera-advanced-cancer-detection/patients/.

Additional Resources

Having support is critical for bladder cancer survivorship. The Bladder Cancer Advocacy Network helps people living with bladder cancer or caring for someone with bladder cancer find community, resources, and tools and tips.

Disclaimer

Signatera has been developed and its performance characteristics determined by the CLIA-certified laboratory performing the test. The test has not been cleared or approved by the US Food and Drug Administration (FDA). CAP accredited, ISO 13485 certified, and CLIA certified. © 2022 Natera, Inc. All Rights Reserved.

References

¹CDC. Bladder Cancer. Accessed April 20, 2022. https://www.cdc.gov/cancer/bladder/index.htm

²ASCO. Bladder Cancer: Introduction. Accessed April 20, 2022. https://www.cancer.net/cancer-types/bladder-cancer/introduction

³American Cancer Society. What Is Cancer? Accessed April 20, 2022. https://www.cancer.org/treatment/understanding-your-diagnosis/what-is-cancer.html

⁴Isharwal S, et al. Non-muscle invasive bladder cancer risk stratification. Indian J Urol. 2015;31(4):289-296. https://doi.org/10.4103/0970-1591.166445

⁵Tang DH, et al. Management of carcinoma in situ of the bladder: best practice and recent developments. Ther Adv Urol. 2015;7(6):351-364. https://doi.org/10.1177/1756287215599694

⁶Sam P, et al. Anatomy, abdomen and pelvis, bladder detrusor muscle. In: StatPearls. StatPearls Publishing; 2021. https://pubmed.ncbi.nlm.nih.gov/29489195/

⁷ Krishna SR, et al. Current concepts in the management of muscle invasive bladder cancer. Indian J Surg Oncol. 2017;8(1):74-81. https://doi.org/10.1007/s13193-016-0586-1

⁸American Cancer Society. Bladder Cancer Risk Factors. Accessed April 20, 2022. https://www.cancer.org/cancer/bladder-cancer/causes-risks-prevention/risk-factors.html

⁹American Cancer Society. Key Statistics for Bladder Cancer. Accessed April 20, 2022. https://www.cancer.org/cancer/bladder-cancer/about/key-statistics.html

¹⁰Marks P, et al. Female with bladder cancer: what and why is there a difference? Transl Androl Urol. 2016;5(5):668-682. https://doi.org/10.21037/tau.2016.03.22

¹¹ASCO. Bladder Cancer: Risk Factors. Accessed April 21, 2022. https://www.cancer.net/cancer-types/bladder-cancer/risk-factors

¹²Harper HL, et al. Upper tract urothelial carcinomas: frequency of association with mismatch repair protein loss and lynch syndrome. Mod Pathol. 2017;30(1):146-156. https://doi.org/10.1038/modpathol.2016.171

¹³American Cancer Society. Can Bladder Cancer Be Prevented? Accessed April 20, 2022. https://www.cancer.org/cancer/bladder-cancer/causes-risks-prevention/prevention.html

¹⁴American Cancer Society. Bladder Cancer Signs and Symptoms. Accessed April 20, 2022. https://www.cancer.org/cancer/bladder-cancer/detection-diagnosis-staging/signs-and-symptoms.html

¹⁵Matulewicz RS, et al. Blood in the urine (hematuria). JAMA. 2016;316(14):1508. https://doi.org/10.1001/jama.2016.4716

¹⁶American Cancer Society. Bladder Cancer Surgery. Accessed April 21, 2022. https://www.cancer.org/cancer/bladder-cancer/treating/surgery.html

¹⁷ASCO. Bladder Cancer: Types of Treatment. Accessed April 21, 2022. https://www.cancer.net/cancer-types/bladder-cancer/types-treatment

¹⁸American Cancer Society. Chemotherapy for Bladder Cancer. Accessed April 21, 2022. https://www.cancer.org/cancer/bladder-cancer/treating/chemotherapy.html

¹⁹Bajorin DF, et al. Adjuvant nivolumab versus placebo in muscle-invasive urothelial carcinoma. N Engl J Med. 2021;384(22):2102-2114. https://doi.org/10.1056/NEJMoa2034442

²⁰National Cancer Institute. Bladder Cancer Treatment (PDQ®)–Patient Version. Accessed April 21, 2022. https://www.cancer.gov/types/bladder/patient/bladder-treatment-pdq

²¹Raphael MJ, et al. Neoadjuvant chemotherapy for muscle-invasive bladder cancer: Underused across the 49th parallel. Can Urol Assoc J. 2019;13(2):2931. https://doi.org/10.5489/cuaj.5827

²²National Cancer Institute. Cancer Stat Facts: Bladder Cancer. Accessed April 21, 2022. https://seer.cancer.gov/statfacts/html/urinb.html

²³Powles T, et al. ctDNA guiding adjuvant immunotherapy in urothelial carcinoma. Nature. 2021;595(7867):432-437. https://doi.org/10.1038/s41586-021-03642-9

²⁴Christensen E, et al. Early Detection of metastatic relapse and monitoring of therapeutic efficacy by ultra-deep sequencing of plasma cell-free DNA in patients with urothelial bladder carcinoma. J Clin Oncol. 2019;37(18):1547-1557. https://doi.org/0.1200/JCO.18.02052

²⁵Bratman SV, et al. Personalized circulating tumor DNA analysis as a predictive biomarker in solid tumor patients treated with pembrolizumab. Nat Cancer. 2020;1(9):873-881. https://doi.org/10.1038/s43018-020-0096-5