Treatment of Bladder Cancer, Based on the Stage and Other Factors

The treatment of bladder cancer is based mainly on the clinical stage of the cancer when it’s first diagnosed. This is your doctor’s best estimate of how far the cancer has grown, based on the exams and tests done so far. The stage takes into account how deeply the cancer is thought to have grown into the bladder wall and if it has spread beyond the bladder.

Other factors, such as the size of the tumor, how fast the cancer cells are growing (the grade of the cancer), and how many tumors there are, are also important, especially for non-muscle invasive bladder cancers (NMIBCs), which are earlier-stage cancers that haven’t yet invaded the muscle layer of the bladder wall. These factors can be used to determine the risk group of the cancer, which, in turn, can affect treatment options.

Still other factors, such as your overall health and preferences, can also affect your treatment options.

Treating non-muscle invasive (stage 0 and stage I) bladder cancers

Non-muscle invasive bladder cancers (NMIBCs) have not yet grown deep enough to reach the muscle layer of the bladder wall. They include:

• Stage 0a: Non-invasive papillary carcinoma (Ta)
• Stage 0is: Non-invasive flat carcinoma (Tis), also known as carcinoma in situ (CIS)
• Stage I: Cancer that has grown into the connective tissue layer of the bladder wall (T1), but that hasn’t reached the muscle layer

Most often, the stage of these cancers is determined when a transurethral resection of the bladder tumor (TURBT) (also known as a transurethral resection, or TUR) is done to remove the tumor(s). Fulguration (using an electrical current to burn the area where the tumor was) might be done during the TURBT. This is typically followed by a dose of intravesical chemotherapy within 24 hours.

Sometimes, a second, more extensive TURBT is done (usually a few weeks later) to help ensure that all the cancer has been removed.

Whether any further treatment is needed mainly depends on which risk group the cancer falls into. This is a measure of how likely the NMIBC is to come back after treatment or to progress to a more invasive cancer.

Low-risk NMIBC

These are single, small, low-grade, papillary (Ta) tumors.

Usually, no further treatment is needed for these tumors.

Cystoscopy is then done regularly to watch for any signs that the cancer might have come back and to look for new tumors. This is usually about every 3 months to start with, but the time between exams can be extended if no new tumors are found.

In some situations, imaging tests of the rest of the urinary tract might also be done to check for new tumors.

Intermediate-risk NMIBC

These NMIBCs typically have one concerning feature, such as the tumor being larger or high grade, or growing into the connective tissue layer (T1); there being more than one tumor; or a tumor that has recurred (come back).

Most often, intravesical therapy (either BCG or chemotherapy) is recommended after the TURBT. It is typically started a few weeks later and is given once a week for about 6 weeks. Sometimes intravesical therapy is continued as maintenance therapy over the next year to try to keep the cancer from coming back.

Another option after TURBT might be close follow-up with regular cystoscopies and other tests, without further treatment.

High-risk NMIBC

These NMIBCs typically have more than one concerning feature, such as the tumor being both high grade and either flat (CIS) or growing into the connective tissue layer (T1).

A second TURBT might be done (usually a few weeks after the first one) to help ensure that the cancer hasn’t reached the muscle layer of the bladder wall. The main treatment options after TURBT include:

• Intravesical therapy with BCG, weekly for 6 weeks, then less frequently for up to 3 years
• Radical cystectomy (surgery to remove the bladder), especially for tumors with very high-risk features

If BCG isn’t effective, other treatment options might include:

• Cystectomy
• Intravesical immunotherapy with nadofaragene firadenovec (Adstiladrin)
  or nogapendekin alfa inbakicept (Anktiva)
• Intravesical chemotherapy
• Treatment with the immunotherapy drug pembrolizumab (Keytruda)

Follow-up and outlook after treatment of NMIBC

After treatment for NMIBC, close follow-up is needed (especially if the bladder hasn’t been removed), with cystoscopy about every 3 months for a least a couple of years to look for signs of the cancer coming back or new bladder tumors.

The outlook for people with low-risk NMIBC tends to be very good. These cancers can almost always be cured with treatment. During long-term follow-up care, more superficial cancers might be found in the bladder or in other parts of the urinary system. Although these new cancers do need to be treated, they rarely are deeply invasive or life-threatening.

The long-term outlook for intermediate- or high-risk NMIBC is not quite as good as for low-risk cancers. These cancers have a higher risk of coming back, and they may return as a more serious cancer that's growing into deeper layers of the bladder or has spread to other parts of the body.

Treating stage II bladder cancer

These cancers have invaded the muscle layer of the bladder wall (T2a and T2b), but they have not grown any farther.

Transurethral resection (TURBT) is typically the first treatment for these cancers, but it's done to help determine the extent (stage) of the cancer rather than to try to cure it.

Treatment options after the TURBT might include: 

• Neoadjuvant chemotherapy that includes the drug cisplatin, followed by radical cystectomy (removal of the bladder)
• Neoadjuvant chemotherapy that includes cisplatin, followed by partial cystectomy (removal of the part of the bladder wall that contains the tumor). This is only likely to be an option for certain tumors that are only in one part of the bladder.
• Cystectomy alone, for people who can’t get cisplatin
• A more extensive TURBT, followed by chemoradiation, for people who can’t have or don’t want a radical cystectomy. This is known as bladder-preserving trimodality therapy.
• Radiation therapy or TURBT alone, for people who can’t have a cystectomy or get chemoradiation.

For people getting a cystectomy, chemo is usually given before surgery because it's been shown to help people live longer than surgery alone.

If cancer is found in nearby lymph nodes that were removed during surgery, or if there’s reason to think there’s a high risk that the cancer might come back, radiation therapy may be given after surgery. Other options might include chemo, if it wasn't given before surgery or an immunotherapy drug such as nivolumab (Opdivo).

For people who have not had their bladder removed, frequent and careful follow-up exams are very important. Cystoscopy exams and biopsies are often done during the chemo and radiation treatments. If cancer is still found in the biopsy samples, a cystectomy will likely be needed.

Treating stage III bladder cancer

These cancers have reached the outside of the bladder (T3) and might have grown into nearby tissues or organs (T4) and/or lymph nodes (N1, N2, or N3). They have not spread to distant parts of the body.

Transurethral resection (TURBT) is typically the first treatment for these cancers, but it's done to help determine the extent (stage) of the cancer rather than to try to cure it.

Treatment options after the TURBT might include:

• Neoadjuvant chemotherapy that usually includes the drug cisplatin, followed by radical cystectomy (removal of the bladder)
• Cystectomy alone, for people who can’t get cisplatin
• A more extensive TURBT, followed by chemoradiation, for people who can’t have or don’t want a radical cystectomy. This is known as bladder-preserving trimodality therapy.
• Other medicines, such as the immunotherapy drug pembrolizumab (Keytruda), with or without the antibody-drug conjugate enfortumab vedotin (Padcev), especially for people who can’t get cisplatin. This might shrink the cancer and allow a person to get other treatments such as a cystectomy or chemoradiation.
• Radiation therapy or TURBT alone, for people who can’t have a cystectomy or get chemoradiation.

Chemotherapy (chemo) or other medicines given before surgery (with or without radiation) can often shrink the cancer, which may make surgery easier. These treatments might also kill any cancer cells that have already spread to other areas of the body.

If cancer is found in nearby lymph nodes that were removed during surgery, or if there’s reason to think there’s a high risk that the cancer might come back, radiation therapy may be given to these areas after surgery. Other treatment options might include chemo, if it wasn't given before surgery, or an immunotherapy drug such as nivolumab (Opdivo).

For people who have not had their bladder removed, frequent and careful follow-up exams are very important. Repeat cystoscopy exams and biopsies might be recommended during chemo and radiation treatments. If cancer is still found in the biopsy samples, a cystectomy will likely be needed.

Treating stage IV bladder cancer

These cancers have reached the pelvic or abdominal wall (T4b) and/or have spread to distant lymph nodes (M1a) or other parts of the body (M1b). Stage IV cancers are very hard to get rid of completely.

If the cancer has not spread to distant parts of the body (M0): It’s very unlikely these cancers could be removed completely with surgery, so medicines are usually the first treatment. Treatment options might include:

• The immunotherapy drug pembrolizumab (Keytruda) plus the antibody-drug conjugate enfortumab vedotin (Padcev)
• The immunotherapy drug nivolumab (Opdivo) plus chemotherapy
• Chemotherapy, which usually includes the drug cisplatin, if a person can tolerate it. If not, other chemo drugs might be used.
• Chemotherapy, followed by the immunotherapy drug avelumab (Bavencio)
• Pembrolizumab alone
• Chemoradiation (radiation therapy plus a chemo drug to help it work better)

After a few cycles of treatment, the cancer is typically rechecked with tests such as cystoscopy, TURBT, and imaging tests. Further treatment at this point might include chemotherapy and/or immunotherapy, chemoradiation, or cystectomy (removal of the bladder), if it can be done.

If the cancer has spread to distant parts of the body (M1): It’s very unlikely these cancers could be removed completely with surgery, so medicines are usually the first treatment. Treatment options might include:

• The immunotherapy drug pembrolizumab (Keytruda) plus the antibody-drug conjugate enfortumab vedotin (Padcev)
• The immunotherapy drug nivolumab (Opdivo) plus chemotherapy
• Chemotherapy, which usually includes the drug cisplatin, if a person can tolerate it. If not, other chemo drugs might be used.
• Chemotherapy, followed by the immunotherapy drug avelumab (Bavencio)
• Pembrolizumab alone

After a few cycles of treatment, the cancer will probably be rechecked with tests such as cystoscopy, TURBT, and imaging tests.

If there are no signs of cancer or if it has shrunk significantly, chemoradiation or cystectomy (removal of the bladder) might be an option in some cases. If surgery is an option, it’s important to understand the goal of the operation – whether it’s to try to cure the cancer, to help a person live longer, or to help prevent or relieve symptoms from the cancer.

If the first treatment doesn’t shrink the cancer or if it stops working (or if it does shrink the cancer and cystectomy isn’t an option for some reason), further treatment with medicines (chemo and/or immunotherapy) might still be helpful. Another option might be a targeted therapy drug. (See below for more on further treatment options.)

Because these cancers are hard to cure with current treatments, many experts recommend considering taking part in a clinical trial that’s testing a newer treatment. Talk to your doctor if this is something you think you might be interested in.

Treating bladder cancer that progresses or recurs

If the cancer continues to grow during treatment (progresses) or if it comes back after treatment (recurs), treatment options will depend on where and how much the cancer has spread, what treatments you’ve already had, and your overall health and desire for more treatment. It’s important to understand the goal of any further treatment, such as trying to cure the cancer, slow its growth, or relieve symptoms, as well as the likely benefits and risks.

For instance, non-muscle invasive bladder cancer often comes back in the bladder. A new cancer may be found either in the same place as the original cancer or in other parts of the bladder. These tumors are often treated the same way as the first tumor. But if the cancer keeps coming back, a cystectomy (removal of the bladder) may be needed. For some non-invasive tumors that keep growing even with BCG treatment, other options might include immunotherapy with pembrolizumab (Keytruda) or intravesical therapy either with chemotherapy or with an immunotherapy drug such as nadofaragene firadenovec (Adstiladrin) or nogapendekin alfa inbakicept (Anktiva).

Cancers that spread or recur in distant parts of the body can be harder to remove with surgery, so other treatments, such as chemotherapy, immunotherapy, targeted therapy, or radiation therapy, might be needed. (See “Treating stage IV bladder cancer” above for an idea of what your treatment options might be.)

For more on dealing with a recurrence, see Understanding Recurrence.

At some point, it may become clear that standard treatments are no longer controlling the cancer. If you want to continue getting treatment, your doctor may recommend taking part in a clinical trial of a newer bladder cancer treatment. While clinical trials might not always be the best option for everyone, they can benefit some people with bladder cancer, as well as helping other people in the future.

Even if medicines are no longer controlling the cancer, there might still be other treatments that can be helpful. For example, some treatment options that focus more on preventing or relieving problems the cancer might cause:

• Radiation therapy (or chemoradiation) might shrink or slow the growth of tumors and help relieve symptoms.
• A urinary diversion without cystectomy (making another path for urine to leave the body, without removing the bladder) might be an option to prevent or relieve a blockage of urine that could cause kidney damage.

It’s very important to let your treatment team know about any symptoms you’re having, as there are often ways to help with them.