What Is Non-Muscle Invasive Bladder Cancer (NMIBC)?

The Most Common Kind of Bladder Cancer

Non-muscle invasive bladder cancer, also known as NMIBC, is a subtype of bladder carcinoma. It is also known as a “superficial” bladder cancer. In NMIBC, the cancer hasn’t affected any of the muscle tissue found inside the bladder. This contrasts with another subtype, muscle-invasive bladder cancer (MIBC), in which the cancer can be found in the muscular wall of the bladder.

Bladder cancers as a group are the most common kinds of cancers involving the urinary tract. Of people newly diagnosed with bladder cancer, around 70% have NMIBC. Bladder cancer is about three times more common in men than in women. It is most common in people aged 50-70.

Verywell / Brianna Gilmartin

Types of Non-Muscle Invasive Bladder Cancer
NMIBC can be broken down into smaller cancer subtypes. These give more information about the specifics of your NMIBC.

Cancer Stage
The different stages of NMIBC give details about the cancer’s appearance, size, and likelihood to spread and respond to certain therapies.

Your cancer might be classified as stage Ta (papillary) if it has finger-like projections and only involves the inner bladder layer found right next to the urine. This is the most common subtype. If the cancer reaches into the layer just below, it’s usually classified as T1. A third type is “carcinoma in situ.” The cells look more abnormal, and the appearance is reddish and flat, but they aren’t invading more deeply.

By definition, people with NMIBC do not have a higher-stage cancer, because the cancer has not spread into nearby tissues or lymph nodes.

Cancer Grade
You might also receive information about your cancer’s “grade.” The grade gives information about how normal the cells appear under a microscope. Cells that appear very disorganized and abnormal are more likely to cause problems. A higher grade is given to cells that appear more abnormal.

The World Health Organization distinguishes low-grade and high-grade NMIBC grades. High-grade NMIBC is more likely to come back after treatment or invade surrounding tissue compared to low-grade NMIBC.

You might learn of other specific characteristics of your MNIBC lesion that relate to your grade as well. For example, if you have a urothelial papilloma grade of MNIBC, the lesion is benign and very unlikely to cause problems. In contrast, if your grade is “high-grade papillary urothelial carcinoma,” that is a more serious type of NMIBC.

Risk Groupings
Some people also further characterize NMIBC into low-risk, intermediate-risk, and high-risk categories, based on grade, stage, and other factors. Those in the highest-risk group have the biggest risk of cancer recurrence, progression, and death. In general, people diagnosed with NMIBC have lower risk of death and bad outcomes compared to people initially diagnosed with MIBC.

NMIBC Symptoms
The most common initial symptom of NMIBC is the appearance of blood in your urine. This is painless, and the blood might not always be present. About 85% of people with bladder cancer will have this symptom. Some people might also have tiny amounts of blood in the urine that aren’t visible with the naked eye.

Some other potential symptoms include:

* Strongly feeling like you need to urinate, even though your bladder isn’t full

* Needing to urinate more frequently

* Pain with urination

* Feeling like you can’t get all the urine out of your bladder

Weak or intermittent urine stream

However, it’s important to note that some people with NMIBC won’t notice any symptoms at all. Also, these symptoms can be found in other medical conditions that have nothing to do with bladder cancer, so it’s important not to jump to conclusions.

The causes of any cancer are complex, and this includes NMIBC. NMIBC develops due to a variety of specific genetic mutations that can occur in the cells in this area of the body. These acquired mutations aren’t present from birth but come as a series of “genetic hits” when a specific part of the DNA becomes damaged. When specific genes become damaged, they might not be able to regulate the cell’s division, replication, and other functions the way they normally would. As they acquire more genetic changes, these cells start to behave more and more abnormally, and they may start to invade neighboring tissue.

Certain environmental conditions increase the likelihood that one will get the genetic damage that will ultimately lead to a cancer. These are called carcinogens. For example, we know that smoking triples the risk of getting bladder cancer. This risk decreases after a person quits, but it doesn’t return to normal for many years. People are also at higher risk of cancer recurrence if they continue to smoke after initial treatment.

People working in certain industries also have a higher risk of getting NMIBC or another bladder cancer. Exposure to such substances as aniline dyes and benzidine compounds can increase risk. This increases risk for people working in fields like printing, iron and aluminum processing, and gas and tar manufacturing.

Chronic irritation to the bladder also increases one’s risk. For example, this might apply to people who have long-term urinary catheters, recurrent urinary tract infections or bladder stones, or to people who have undergone chemotherapy in the past. However, some people get NMIBC even if they have no known risk factors for the disease, and many people with these risk factors never get the disease.

People who have had someone in their family with bladder cancer are also at higher risk. This might be due to variations in certain genes that slightly increase one’s risk. It might also be due to shared environmental exposures (like smoking).

Rarely, NMIBC occurs due to inheriting a genetic syndrome that puts one at increased risk of cancer. For example, people with Lynch syndrome have a greatly increased risk of getting certain cancers, including NMIBC.

A standard medical history and clinical exam provide the diagnostic starting points. That often includes a rectal and prostate exam for men and a recto-vaginal exam for women.

You may also need to have your urine samples analyzed. This can help eliminate other possible causes of your symptoms and give clues about possible bladder cancer. Looking at these cells under a microscope can give further information about the nature of your disease. Your urine might also be analyzed for certain protein markers that are often found in people with bladder cancer.

Sometimes ultrasound of the kidneys and bladder can be a helpful next step if you are noticing that you have blood in your urine.

If your clinician is concerned about bladder cancer from these clues, you’ll need a cystoscopic evaluation. Unfortunately, this is a somewhat uncomfortable procedure. During cystoscopy, your physician inserts a long hollow tube up your urethra and into your bladder. This can typically be done at your doctor’s office. During cystoscopy, your clinician can get a look at your bladder and take small tissue samples that can be further analyzed in a laboratory. Through these analyses, you can learn whether you have NMIBC and what subtype you might have.

In some cases, further imaging will be needed to get more information about the extent of your cancer. This might include computed tomography urography, intravenous urogram, or pelvic and abdominal magnetic resonance imaging (MRI).

The current standard treatment for most people with NMIBC is a therapy called TURBT (transurethral resection of bladder tumor). This treatment removes all the visible cancer and can provide more information on whether the cancer has spread. The samples can also be further analyzed, yielding more information about the specifics of the cancer. Some people need an additional TURBT procedure after their first one. For example, this might be recommended for people with higher grade tumors.

TURBT is often accompanied by treatment that’s given through intravesical therapy. Intravesical therapy just means that the drug is put in through a soft catheter that leads directly to the interior of your bladder. That helps the treatment reach the affected areas without having to impact the other cells of your body. Intravesical therapy might reduce the chance that the cancer will come back.

Mitomycin C (MMC) is one potential option for intravesical therapy. It is the most commonly used type of chemotherapy in this context.

For intermediate- and high-risk NMIBC, clinicians often recommend intravesical therapy of BCG (Bacillus Calmette-Guerin). This is a type of immunotherapy derived from a germ related to the one that causes tuberculosis. BCG helps turn on the immune system so that these cells attack the cancerous cells. Depending on the situation, you might receive only one intravesical therapy, or you might have multiple treatments over several months.

People with NMIBC will also need follow-up cystoscopy, to make sure that the cancer hasn’t come back. Unfortunately, in many people with NMIBC, the cancer returns after treatment. Often it comes back at the same cancer stage about six months to a year later. At that point, you might need further therapy to get the disease under control, perhaps using a different sort of intravesical treatment or radiation.

If these follow-up treatments don’t work, you might ultimately need surgery to remove the bladder (cystectomy). Cystectomy is also usually necessary for people who develop cancer that invades the muscle wall or spreads around the body more broadly. About 10% to 15% of people with NMIBC eventually develop this kind of cancer. These individuals usually need other treatments like additional chemotherapy and immunotherapy.

In men, cystectomy usually involves completely removing the bladder as well as the prostate and seminal vesicles. In women, it usually requires removing the bladder, uterus, ovaries, and part of the vagina. During the procedure, the surgeon creates a new route for urine to leave the body in a process called urinary diversion. Depending on the exact type of surgery, you might be able to urinate relatively normally afterward. In other cases, you might need to use a catheter to drain your urine yourself or have a bag outside your body that collects your urine.

Some people with NMIBC respond very well to treatment and experience no follow-up symptoms. However, even with the best treatments available, some people do die of the disease. Researchers are actively exploring many different treatment modalities to help more people recover from NMIBC and live high-quality lives.

Written by Ruth Jessen Hickman, MD for Very Well Health, April 21, 2020

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