Non-muscle-invasive bladder cancer (NMIBC) is a common type of cancer, but each person’s experience with it is unique. If you or a loved one has been diagnosed with NMIBC, your healthcare team will tell you if the cancer is considered high risk or low risk. About 25 percent of people diagnosed with NMIBC have high-risk cancer.

Healthcare providers sort people into risk groups by comparing test results to cancer statistics from many others with NMIBC. They may also consider your overall health, tumor characteristics, and treatment history.

In this article, we’ll explain how your risk is assessed and what it means to be diagnosed with high-risk NMIBC.

NMIBC Stage and Grade

In non-muscle-invasive bladder cancer, the cancer has not grown into the muscle layer of the bladder wall. One of the first steps in assessing NMIBC involves figuring out the stage and grade.

Many urologists and oncologists use the TNM cancer staging system to describe how far the cancer has spread. “TNM” stands for:

• Tumor — How big the tumor is and how deep it has grown into the bladder wall
• Nodes — Whether the cancer has spread to nearby lymph nodes
• Metastasis — Whether the cancer has spread to other parts of the body

To find out the cancer grade — how likely it is to grow and spread — a pathologist (a doctor who studies cells under a microscope) will look at the cancer cells. High-grade cancers have cells that look very abnormal and are more likely to spread and recur (come back). Low-grade cancers look more like normal cells and usually grow more slowly.

Facts About High-Risk NMIBC

To determine your NMIBC risk group, your healthcare team will collect a range of information. This includes your medical history, a physical exam, and several lab and imaging tests. They’ll look at the cancer’s stage, grade, tumor size, and other features to see if it’s in the high-risk category.

Below are some key facts about how high-risk NMIBC is diagnosed — and what that means for your treatment options and outlook.

1. Calculating NMIBC Risk Involves Many Tests

Your healthcare team will use the results of several tests to confirm NMIBC, determine your risk group, and help you plan next steps. Here are some of the most common tests, which are usually done in this order:

Cystoscopy

A cystoscopy uses a long, thin, flexible tube with a camera on the end, inserted via the urethra, to look inside your bladder. This helps your doctor see any tumors and do a biopsy (take a tissue sample to be tested at a lab).

Transurethral Resection of Bladder Tumor

A transurethral resection of bladder tumor (TURBT) can both diagnose and treat bladder cancer. During this procedure, a surgeon also inserts a long, flexible tube via the urethra, removes any visible tumors, and takes small samples of the bladder muscle. These samples are then sent to a lab to help determine the cancer stage. A cystoscopy and TURBT are usually done at the same time if a tumor is identified.

Biopsy Analysis

Tumor samples collected during cystoscopy or TURBT are sent to a pathology lab to be analyzed and assigned a grade by a pathologist.

Genomic/Biomarker Testing

Cancer cells or blood samples are sometimes sent for genomic testing — also called biomarker or molecular testing. These tests look for specific gene mutations (changes) or proteins in the cancer cells. This information can help guide your treatment plan, especially if your bladder cancer is more advanced.

2. Different Types of NMIBC Tumors Can Be High Risk

High-risk NMIBC isn’t just one type of tumor. Instead, it’s a group of cancers with certain features that make them more likely to come back or spread. Specialists update the guidelines for what counts as high-risk NMIBC as new research comes out.

Your risk group can also change over time. As you get treatment, your healthcare team might learn more about your cancer by doing more tests or by seeing whether your cancer comes back.

According to current American Urological Association guidelines, any of the following findings are classified as high-risk NMIBC:

• A high-grade tumor that has grown past the bladder’s inner lining into the layer of connective tissue (the support layer just under the bladder’s inner lining)
• A high-grade, early-stage tumor that has come back after treatment
• A high-grade, early-stage tumor larger than 3 centimeters
• More than one high-grade, early-stage tumor found at the same time
• Carcinoma in situ (an early-stage tumor that tends to be more aggressive)
• Presence of cancer cells in the small blood or lymph vessels (small channels that carry a clear fluid called lymph) in the removed bladder tissue
• The presence of cancer cells in the part of the urethra that passes through the prostate
• A high-grade cancer that doesn’t respond to Bacillus Calmette-Guerin (BCG) immunotherapy

3. High-Risk Cancer Is More Likely To Spread and Recur

Knowing your risk group helps your healthcare team understand what your bladder cancer might do. High-risk NMIBC is more likely than low-risk NMIBC to grow and spread, which is called disease progression. High-risk NMIBC is also more likely to recur after treatment.

High-risk NMIBC is more likely than low-risk NMIBC to grow and spread.

A 2023 review looked at 12 studies of people with high-risk NMIBC to estimate the risk of recurrence. Over a five-year period, the recurrence rate ranged from 17 percent to 89 percent. The risk was lower in people who had completed longer courses of BCG immunotherapy. People had a higher chance of the cancer coming back if they had larger tumors, more than one tumor, or a previous recurrence.

The same study also looked at the risk of cancer spreading. After five years, the chance that high-risk NMIBC would not progress after treatment was between 58 percent and 89 percent.

Read more about which factors affect your outlook with NMIBC.

4. High-Risk NMIBC Has Specific Treatment Guidelines

Treatment for high-risk NMIBC usually involves longer courses of treatment compared to those for other risk groups. You’ll also need more frequent checkups after treatment to monitor for signs of recurrence.

With high-risk NMIBC, you'll need more frequent checkups after treatment to monitor for signs of recurrence.

Treatment of low- to intermediate-risk NMIBC usually begins with TURBT, followed by close observation or intravesical chemotherapy, particularly for intermediate-risk NMIBC.

For high-risk NMIBC, the next step after TURBT is typically BCG intravesical immunotherapy, which is placed directly into the bladder (“intravesical” means “within the bladder”). At first, BCG therapy is usually given once a week for six weeks, a phase called induction therapy.

After that, you’ll likely start maintenance therapy — weekly BCG treatments for three weeks at three months, six months, and then every six months for up to three years. If BCG therapy causes serious side effects or isn’t available, your doctor might recommend intravesical chemotherapy.

After treatment, you’ll need regular follow-ups with your healthcare team to monitor for signs of tumor recurrence. Most people are checked every three months for two years, then twice a year for three or four years, and finally once a year after that.

It’s important to follow your full treatment plan and go to all of your checkups. Studies show that people who don’t do this have worse results — their cancer is more likely to come back, spread, or affect how long they live.

5. NMIBC That Doesn’t Respond to BCG Therapy Is High Risk

For about 30 percent to 50 percent of people treated with BCG for NMIBC, BCG intravesical therapy doesn’t work. This is called BCG unresponsiveness. A lack of response can take different forms, including tumors that:

• Don’t shrink or go away during therapy
• Appear during BCG treatments
• Come back within six months after BCG maintenance therapy is complete

BCG intravesical therapy doesn’t work for about 30 percent to 50 percent of people with NMIBC.

If your cancer is high-grade and doesn’t respond to BCG therapy, it’s considered high-risk NMIBC, even if it was previously thought to be low risk. When this happens, your treatment options will likely change. If you are also intolerant to BCG because of a previous allergic reaction or another side effect, other treatment options may be offered to you.

One common approach is radical cystectomy (surgery to remove the bladder) to help prevent the cancer from spreading. However, due to other health conditions or personal reasons, not everyone can have this surgery. New immunotherapy and drug options have been approved to treat some cases of BCG-unresponsive cancer.

Clinical trials, which look at the safety and effectiveness of new drugs in humans, are also testing other types of treatments. Talk to your urology team about the best options for you, including whether a clinical trial might be a good fit.

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