When a bladder tumor grows, it typically begins in the bladder’s inner lining and spreads outward. If left untreated, cancer cells may grow deeper into the bladder wall and nearby tissues. Urologists, who treat urinary system conditions, and oncologists, who treat cancer, classify bladder cancer based on how far it has spread and how deeply it has grown into the bladder wall.

Bladder cancer that remains confined to the bladder lining is called non-muscle-invasive bladder cancer (NMIBC). Cancer that spreads into the bladder’s muscle wall is called muscle-invasive bladder cancer (MIBC). NMIBC is an earlier stage of bladder cancer, while MIBC is more advanced.

Around 75 percent of people diagnosed with bladder cancer have NMIBC. The remaining 25 percent are diagnosed with muscle-invasive disease. These two forms differ in how aggressive they are, how they’re treated, and what outcomes are expected. In this article, we’ll explain the differences between NMIBC and MIBC.

MIBC Is a Later-Stage, High-Grade Type

A cancer’s stage describes how much cancer is in the body, including the tumor’s size and whether cancer cells have spread from where they first formed. In bladder cancer, staging refers to how deeply the tumor has grown from the inner lining of the bladder into surrounding layers or nearby organs.

NMIBC includes early-stage cancers that have not entered the muscle layer of the bladder wall:

• Ta — The tumor is confined to the inner bladder lining and has not invaded deeper layers.
• Tis — Known as carcinoma in situ (CIS), this is a flat, high-grade cancer that sits on the bladder lining and has not grown into deeper tissue.
• T1 — The tumor has spread into the layer just beneath the lining but not into the muscle.

Muscle-invasive stages include:

• T2 — The tumor has invaded the muscle layer.
• T3 — The tumor has grown through the bladder muscle into the surrounding fatty tissue (perivesical tissue).
• T4 — The tumor has moved to nearby organs in the pelvis, such as the prostate, seminal vesicles, uterus, vagina, or the pelvic or abdominal walls.

Bladder tumors are also described by grade, which refers to how abnormal the cancer cells look under a microscope and how likely they are to grow or spread. High-grade bladder cancers grow and spread more aggressively and are more likely to come back after treatment. Low-grade cancers tend to grow slowly and are less likely to spread.

Non-muscle-invasive bladder cancer is at an earlier stage and may be low grade or high grade. All muscle-invasive bladder cancer is high grade, meaning it's more likely to spread.

Most NMIBC tumors may be low grade or high grade, depending on several factors. Muscle-invasive urothelial bladder cancers are considered high grade.

NMIBC and MIBC Cause Similar Symptoms

The symptoms of NMIBC and MIBC often overlap. Other conditions, like kidney stones or urinary tract infections, can also cause these symptoms. If your healthcare provider suspects you have bladder cancer, they’ll recommend tests to confirm the diagnosis and determine if you have NMIBC or MIBC.

Talk to your healthcare provider if you notice any of these symptoms:

• Blood in your urine (the most common symptom)
• Frequent or urgent need to pee
• Burning or pain when you pee
• Pain in your lower belly or back

NMIBC Treatments Start With TURBT and BCG Immunotherapy

The first-line treatment for NMIBC is usually transurethral resection of bladder tumor (TURBT). During TURBT, a surgeon removes any visible tumors from the bladder using a thin, tubelike tool inserted through the urethra. They may also take tissue samples of the bladder muscle for analysis, called a biopsy. The goal is to remove as much of the cancer as possible.

Next steps depend on whether you have low-, intermediate-, or high-risk NMIBC:

• Low-risk NMIBC may be managed with active surveillance, meaning close monitoring with no immediate treatment.
• Intermediate-risk NMIBC is usually treated with intravesical therapy (medicine put directly into the bladder), such as chemotherapy or BCG, based on your risk factors. In some cases, your doctor may recommend regular checkups and tests instead.
• High-risk NMIBC is often treated with bacillus Calmette-Guérin (BCG) immunotherapy, which is made from a weakened form of the bacteria used in the tuberculosis vaccine. When placed in the bladder, BCG stimulates the immune system to attack cancer cells.

Some people with NMIBC may not respond to BCG. Many treatment options for BCG-refractory bladder cancer are similar to those used for MIBC, described below.

Non-muscle-invasive bladder cancer is usually treated with TURBT surgery, which spares the bladder. People with muscle-invasive bladder cancer are often advised to have their bladder removed.

Immunotherapies for BCG-Refractory NMIBC

For NMIBC that’s not responsive enough to BCG, two other immunotherapies are available — nadofaragene firadenovec (Adstiladrin) and nogapendekin alfa inbakicept (Anktiva). Both are delivered intravesically, like BCG.

Another immunotherapy, pembrolizumab (Keytruda), may be offered if NMIBC doesn’t respond to BCG. This medication is given intravenously (by IV).

MIBC Treatments Start With Bladder Removal and Chemotherapy

BCG treatment is not effective for MIBC. TURBT is often performed to help determine the tumor’s stage and grade, but this procedure alone usually isn’t enough to treat this type of cancer.

Radical cystectomy — surgery to remove the bladder — is the standard treatment for MIBC. During this procedure, a surgeon removes the bladder and nearby lymph nodes. Depending on how far the cancer has spread, they may also remove the prostate and seminal vesicles or the uterus, ovaries, and fallopian tubes. After removing the bladder, the surgeon creates a urinary diversion — a new way for the body to store and remove urine.

To improve outcomes, treatment guidelines from the American Urological Association recommend chemotherapy before cystectomy, called neoadjuvant chemotherapy.

Another option for some people with MIBC is durvalumab (Imfinzi), an immunotherapy that’s given with chemotherapy before surgery and then continued after surgery.

Immunotherapies for Advanced Bladder Cancer

Several immunotherapies are available to treat advanced bladder cancer. These include:

• Avelumab (Bavencio)
• Nivolumab (Opdivo)
• Pembrolizumab

Targeted Drugs for Advanced Bladder Cancer

If testing shows your bladder cancer cells have certain proteins or genetic changes, you may be offered targeted therapy. These medications work by identifying and attacking specific targets on cancer cells. For instance, Erdafitinib (Balversa) targets proteins called fibroblast growth factor receptors that can encourage cancer to grow. Enfortumab vedotin (Padcev) targets Nectin-4 (an adhesion protein located on the surfaces of bladder cancer cells).

To learn whether you may be a candidate for targeted therapies, ask your doctor if your cancer cells have undergone biomarker testing and what results showed.

NMIBC Has a Better Prognosis Than MIBC

In general, people diagnosed with NMIBC tend to have a better outlook than those with MIBC. Prognosis — or expected outcome — depends on many factors, including the stage and grade of the cancer, how far it has spread, and whether it returns after treatment.

Survival After Diagnosis

According to the National Cancer Institute, the five-year relative survival rate for carcinoma in situ is 97 percent. This means that people with this type of NMIBC are 97 percent as likely to live at least five years after diagnosis as people without bladder cancer.

For localized bladder cancer (when the cancer is only in the bladder), the five-year survival rate is 71 percent. This includes many cases of NMIBC.

People with non-muscle-invasive bladder cancer are more likely to live longer and less likely to experience cancer spreading compared with those who have muscle-invasive cancer.

For MIBC, the survival rate depends on how far the cancer has spread. The five-year survival rate is about 39 percent if the cancer has spread to nearby lymph nodes or organs (regional disease) and 8 percent if it has spread to distant parts of the body (metastatic disease).

It’s important to remember that these statistics describe the summary of outcomes of a large group of individuals. Your outlook may be different depending on your treatment plan, age, overall health, and other personal factors.

Read more about risk factors that affect NMIBC outcomes.

Cancer Progression

“Progression” means that cancer has become more advanced — for example, by growing into deeper layers of tissue or spreading to other parts of the body. The risk of progression is higher with MIBC than with NMIBC. People with MIBC are also more likely to develop metastatic disease.

In NMIBC, how the cancer responds to treatment — especially BCG immunotherapy — can affect the risk of progression. Studies show that about 10 percent to 20 percent of people whose cancer responds well to BCG eventually experience progression. For people whose NMIBC doesn’t respond to BCG, the risk rises to about 66 percent.

Cancer Recurrence

Another important measure of cancer outcome is the rate at which cancer recurs (comes back). In people with MIBC who have had a cystectomy, the recurrence rate is 5 percent to 15 percent. Recurrence usually happens in the first two years after surgery, but it can happen up to five years later.

If this type of cancer comes back to the pelvis, the prognosis is typically poor. Even with treatment, the median survival after a recurrence is about four to eight months. This means that 50 percent of people will live less than that, and 50 percent will live longer. Certain treatment options can improve survival and relieve symptoms, including combinations of chemotherapy, immunotherapy, targeted therapy, radiation, and surgery. Your urology team can explain whether these options are right for you.

In general, more than 50 percent of people diagnosed with NMIBC will have a recurrence within five years of their first tumor removal. However, most recurrences don’t involve cancer spreading to deeper tissue or other areas. The chance of recurrence depends on the stage and grade of the cancer and how well it responds to treatments like BCG.

Work With Your Doctor To Stay Ahead of Bladder Cancer

Whether you are newly diagnosed or have been living with bladder cancer for years, working closely with your healthcare team is essential. Even after treatment, regular follow-up care is important for staying on top of your health. By tracking changes early and sticking with a personalized care plan, you and your care team can make informed decisions and take steps to protect your health over time.

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