Bladder Cancer

Bladder cancer occurs when abnormal cells grow out of control in the bladder, forming a tumor. The bladder is a hollow organ that holds and releases urine (waste liquid created by the kidneys).

Cancer in the bladder often has no symptoms and produces few effects on the bladder itself, although there may be blood in the urine. It most often produces symptoms and effects if cancer spreads to other areas of the body, which can be serious or even fatal. Treating bladder cancer before it spreads has the best outcomes.

This article will provide an overview of bladder cancer and explain what you should know about its risks.

Types of Bladder Cancer

The three main types of bladder cancer start in different kinds of cells in the bladder or urinary tract. Most bladder cancer develops in the innermost bladder layer. When they first develop, these cancers are in that layer only. At this point, they’re called carcinoma in situ or stage 0 cancer.

When these cancers grow, they can spread into other bladder layers. They may also be classified as superficial bladder cancer, invasive bladder cancer, or non-muscle invasive bladder cancer. 

As they spread farther, these cancers grow into the bladder muscles. These spreading cancers are called muscle-invasive bladder cancers. Bladder cancers that have spread into the muscles are more likely to spread farther and are harder to treat.

Transitional Cell Carcinoma

The most common type of bladder cancer, which starts in the urothelial cells, is called transitional cell carcinoma or urothelial carcinoma. These cells make up the inside of the bladder, which is in contact with urine.

Urothelial cells are also present in other areas of the urinary tract, including the ureters, urethra, and kidney parts. These cells can also develop cancers in these different areas of the urinary tract.

Squamous Cell Carcinoma

A very small number of bladder cancers develop from squamous cells. These cells look flat and are often found on the surface of the skin or other organs. They're also found in the innermost layer of the bladder. When they become cancerous, they’re called squamous cell carcinoma. Up to 2% of bladder cancers are squamous cell carcinomas.

Adenocarcinoma

Adenocarcinoma cancers form in the glands of the bladder or urinary tract. These make up only 1% of bladder cancers.

Bladder Cancer Symptoms

Bladder cancer can be found early but does not always show symptoms. The most common symptom of bladder cancer is blood in the urine, called hematuria. The urine may look pink, orange, or dark red.

Other signs and symptoms of advanced bladder cancer include:

• Inability to urinate (pee)
• Pain in one side of the lower back
• Reduced appetite 
• Unexplained weight loss 
• Being tired or weak
• Swelling (typically of the feet)
• Bone pain

Early Signs of Bladder Cancer

The most common early symptoms of bladder cancer are those related to changes in urination:

• Bloody urine
• Peeing more than usual
• Pain or burning when urinating
• Feeling a need to urinate when the bladder isn’t full
• A weak urine stream 
• Trouble getting urine out
• Getting up to pee many times a night

Other health issues also cause these symptoms, including urinary tract infections, bladder stones, or an enlarged prostate. See a healthcare provider if you have these symptoms.

What Causes Bladder Cancer?

Cancers develop when changes happen to the genetic material inside of cells, allowing them to grow and divide out of control.

Factors like radiation and light, cancer-causing chemicals, or infections can cause these genetic changes. In some cases, they’re more common because of preexisting genetic changes that make people more sensitive to these factors.

Experts don’t know what causes most cases of bladder cancer. Some cases of bladder cancer may be hereditary and caused by inherited gene mutations, but these are rare. They include:

• Genetic changes in the retinoblastoma RB1 gene increase the risk of bladder cancer.
• Changes in the PTEN gene cause Cowden disease, which increases the risk of bladder cancer.
• Lynch syndrome increases the risk of bladder cancer and other urinary tract cancers.

Factors that increase the risk of developing bladder cancer include:

• Smoking tobacco: Increases risk by a factor of 3
• Drinking alcohol
• Exposure to aromatic amines and other cancer-causing chemicals, typically in a workplace.
• Supplements containing aristolochic acid
• Long-term high-dose use of diabetes medicine Actos (pioglitazone)
• Chemotherapy drug Cytoxan (cyclophosphamide)
• Arsenic
• Chronic dehydration
• Chronic bladder irritation or infection
• Being over 55 
• Being male
• Having a congenital (present at birth) disability of the bladder

Bladder cancer is diagnosed twice as often in non-Hispanic White people as in Black or Hispanic people in the United States.

How Does Bladder Cancer Spread?

Bladder cancer spreads from the innermost layer of the bladder lining to the outer layers, which include a layer of connective tissue and an outer layer of smooth muscle.

The most common sites for spread outside of the bladder (metastasis) of urothelial carcinoma of the bladder are the lymph nodes, bone, other urinary tract sites, lungs, and liver.

How Is Bladder Cancer Diagnosed?

If you have concerning symptoms, a healthcare provider will take a complete personal and family history, do a physical exam, and request various tests to diagnose bladder cancer. These tests include:

• Urine tests look for blood, cells, bacteria, and chemical signals of cancer.
• Cystoscopy examines the bladder using a cystoscope, a thin, flexible tube with an attached video camera.
• During a cystoscopy, they may take a tissue sample called a bladder biopsy. A bladder biopsy may also be called a transurethral resection of a bladder tumor or transurethral resection.
• Other imaging tests like an X-ray, computed tomography (CT) scan, ultrasound, or magnetic resonance imaging (MRI) to look for cancer inside the body.

Bladder Cancer Stages

Cancers are staged for healthcare providers to track how similar cancers progress and how well treatments work. Bladder cancer has five stages, starting at stage 0. The higher the stage number, the more serious the diagnosis and the worse the prognosis.

TNM Staging System

As researchers have learned more about cancer's genetic and molecular factors, staging many cancers has become complicated. But generally, they follow the TNM staging system:

• "T" stands for "tumor" and defines how large the original tumor is. T is staged from 0 to 4, and special categories of Ta (noninvasive papillary carcinoma, a finger-like projection into the bladder) and Tis (in situ)
• "N" stands for "nodes" and defines how many lymph nodes the cancer has spread to. N is staged from 0 to 3
• "M" stands for "metastasis" and defines if cancer has spread to other organs or tissues. M is either 0 or 1

An X means that that characteristic couldn't be measured.

Stage Groups

The five stages of bladder cancer are:

• Stage 0 bladder cancers are flat or form fingerlike projections that have not spread farther into the bladder than the innermost layer.
• Stage 1 bladder cancers have invaded the second layer of the bladder (the connective tissue) but have not spread to any lymph nodes.
• Stage 2 bladder cancers have invaded the muscle of the bladder but have not spread to any lymph nodes.
• Stage 3 bladder cancers have spread to surrounding tissues or organs and may have also spread to one or more lymph nodes in the abdomen. 
• Stage 4 bladder cancers have spread to the wall of the abdomen, lymph nodes outside of the abdomen, or other body organs. Metastatic bladder cancer commonly spreads to the bones, the lungs, or the liver.

Bladder Cancer Grade

When the pathologist in the lab analyzes bladder tissue taken from a biopsy, they examine how the cells look and how many of them are dividing to give cancer a grade. Bladder cancers are typically grouped as either low-grade or high-grade cancers.

Low-grade cancers are also called well-differentiated cancers. They look pretty standard under the microscope. Low-grade cancers are slower growing, less likely to spread, and have a better prognosis than high-grade cancers. 

High-grade cancers are called poorly differentiated or undifferentiated. They look less regular and more wild. Many of the cells in the tumor are multiplying, and these cancers typically grow faster and spread more quickly than low-grade cancers. They are harder to treat and have a worse prognosis, also.

Bladder Cancer Treatment

Bladder cancer treatment typically involves surgery, chemotherapy, immunotherapy, and radiation. The best course of action will depend on your cancer stage, overall health, and treatment goals.

Surgery

One of the main approaches to treating bladder cancer is surgery. Surgery involves an operation to cut out cancer. Procedures may include:

• Transurethral resection with fulguration removes cancer directly using a small tube through the urethra with a camera and an electric loop. The loop is used to cut away cancer.
• Partial cystectomy is surgery to remove part of the bladder. It’s an option when cancer has invaded the muscle but only in one area. 
• Radical cystectomy with urinary diversion removes the whole bladder and potentially also some nearby organs and tissues. Because the bladder is removed, urine must be diverted to either the colon, a catheter, or a bag outside the abdomen.

Chemotherapy

Chemotherapy is medicine that kills fast-growing cells. Cancer cells are fast-growing, though some other body cells are, too, like mucous membranes and hair cells. Chemotherapy kills these cells or stops them from dividing. It may be used alone or with other treatments. It may be given before or after surgery.

Since the bladder is a hollow organ, a type of treatment called intravesical chemotherapy can be used. This puts chemotherapy directly into the bladder to treat the cells in place instead of sending the medicine throughout the body. This reduces the side effects. This approach may be used after surgery.

For more invasive bladder cancer, systemic chemotherapy (works throughout the body) can be used before surgery, after surgery, or as primary therapy for advanced disease.

Immunotherapy

Immunotherapies use your body's natural defenses against cancer. Several monoclonal antibody treatments are used for bladder cancer that activates the immune system.

Bacillus Calmette-Guerin (BCG) treatment is a unique immunotherapy for bladder cancer. Liquid containing a species of weakened Mycobacterium bacteria is introduced to the bladder via a thin tube (catheter). BCG bacteria are also used in a tuberculosis vaccine. The treatment stimulates the body's defenses and helps it fight cancer.

If BCG therapy is unsuccessful, another treatment option includes Adstiladrin (nadofaragene firadenovec-vncg). Adstiladrin is the first gene therapy approved for adults with high-risk, non-muscle invasive bladder cancer (NMIBC) that hasn't responded to the standard treatment, BCG.

Radiation Therapy

Radiation uses high-energy beams to break down cancer cells. It may be used alone or with other treatments. It may be given before or after surgery.

Targeted Therapy

Targeted therapies may be used to treat bladder cancer that has come back after treatment. Based on their cancer's molecular characteristics, these therapies help the body attack cancer cells. It may require biomarker testing to determine if targeted therapy is an option for your bladder cancer.

Is Bladder Cancer Curable?

Some early-stage bladder cancers that are superficial and non-muscle-invasive can be cured with surgery and other treatments. Sometimes, even bladder cancers that have invaded the muscle can be cured.

In many cases in which the original cancer has been successfully treated, the person will get another bladder or urinary tract tumor. This cancer may be a result of the original cancer coming back (recurrence), or it can be a second bladder cancer unrelated to the first.

One study reported recurrence rates for non-muscle invasive bladder cancer to be over 50%, and even higher for intermediate-risk and high-risk cases.

Can You Prevent Bladder Cancer?

It is not possible to prevent bladder cancer completely. You can’t control your genetic predisposition to cancer, age, race, or family history. But you can do some things to reduce your risk of developing it. They include not smoking and avoiding chemicals in the workplace. You’ll also want to drink plenty of fluids and eat many fruits and vegetables.

Bladder Cancer Outlook

According to data from 2012 to 2018, 77.1% of people diagnosed with bladder cancer are alive five years later. It is estimated that 17,100 people died of bladder cancer in 2022. That’s 2.8% of all cancer deaths. Bladder cancer death rates have fallen around 1.1% annually between 2011 and 2020.

The outlook for people with bladder cancer depends heavily on the cancer stage when diagnosed:

• In situ bladder cancer is still only in the layer of the bladder it started in. It has a high survival rate, with 96% of people alive five years later.
• Localized bladder cancer has spread to other parts of the bladder. An estimated 69.6% of people diagnosed with it are alive five years later.
• Regional bladder cancer has spread to other organs or lymph nodes in the abdomen. Only 39% of patients with regional bladder cancer are alive five years later.
• Distant bladder cancer has spread to other organs in the body. Only 7.7% of people with distant bladder cancer are alive five years after diagnosis. 

Thankfully, 85% of bladder cancers are found before they reach the regional stage. The earlier a cancer is caught, the easier it is to treat and the better a person’s outlook.

Statistics do not represent individual cases, and treatments for bladder cancer are constantly improving. Talk with a healthcare provider about your individual prognosis and treatment options.