Treatment of Bladder Cancer, by Stage

Most often, treatment of bladder cancer is based on the tumor’s clinical stage when it's first diagnosed. This includes how deep it's thought to have grown into the bladder wall and whether it has spread beyond the bladder. Other factors, such as the size of the tumor, how fast the cancer cells are growing (grade), and a person’s overall health and preferences, also affect treatment options.

Treating stage 0 bladder cancer

Stage 0 bladder cancer includes non-invasive papillary carcinoma (Ta) and flat non-invasive carcinoma (Tis or carcinoma in situ). In either case, the cancer is only in the inner lining layer of the bladder. It has not invaded (spread deeper into) the bladder wall.

This early stage of bladder cancer is most often treated with transurethral resection (TURBT) with fulguration followed by intravesical chemotherapy within 24 hours.

Stage 0a

Sometimes no further treatment is needed. Cystoscopy is then done every 3 to 6 months to watch for signs that the cancer has come back.

For low-grade (slow-growing) non-invasive papillary (Ta) tumors, weekly intravesical chemotherapy may be started a few weeks after surgery. If the cancer comes back, the treatments can be repeated. Sometimes intravesical chemo is repeated over the next year to try to keep the cancer from coming back.

High-grade (fast-growing) non-invasive papillary (Ta) tumors are more likely to come back after treatment, so intravesical BCG is often used after surgery. Before it's given, TURBT is commonly repeated to be sure the cancer has not affected the muscle layer. BCG is usually started a few weeks after surgery and is given every week for several weeks. Intravesical BCG seems to be better than intravesical chemotherapy for high-grade cancers. It can help both keep these cancers from coming back and keep them from getting worse. But it also tends to have more side effects. It, too, may be done for the next year or so.

Stage 0 bladder cancers rarely need to be treated with more extensive surgery. Partial or complete cystectomy (removal of the bladder) is considered only when there are many superficial cancers or when cancer continues to grow (or seems to be spreading) despite treatment.

Stage 0is

For flat non-invasive (Tis) tumors, intravesical BCG is the treatment of choice after TURBT. Patients with these tumors often get 6 weekly treatments of BCG, starting a few weeks after TURBT. Some doctors recommend repeating BCG treatment every 3 to 6 months.

Follow-up and outlook after treatment

After treatment for any stage 0 cancer, close follow-up is needed, 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 stage 0a (non-invasive papillary) bladder cancer is very good. These cancers can almost always be cured with treatment. During long-term follow-up care, more superficial cancers are often 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 stage 0is (flat non-invasive) bladder cancer is not quite as good as for stage 0a cancers. These cancers have a higher risk of coming back, and may return as a more serious cancer that's growing into deeper layers of the bladder or has spread to other tissues.

Treating stage I bladder cancer

Stage I bladder cancers have grown into the connective tissue layer of the bladder wall (T1), but have not reached the muscle layer.

Transurethral resection (TURBT) with fulguration is usually the first treatment for these cancers. But it's done to help determine the extent of the cancer rather than to try to cure it. If no other treatment is given, many people will later get a new bladder cancer, which often will be more advanced. This is more likely to happen if the first cancer is high-grade (fast-growing).

Even if the cancer is found to be low grade (slow-growing), a second TURBT is often recommended several weeks later. If the doctor then feels that all of the cancer has been removed, intravesical BCG (preferred) or intravesical chemo is usually given. (Less often, close follow-up alone might be an option.) If all of the cancer wasn't removed, options are intravesical BCG or cystectomy (removal of part or all of the bladder).

If the cancer is high grade, if many tumors are present, or if the tumor is very large when it's first found, radical cystectomy may be recommended.

For people who aren’t healthy enough for a cystectomy, radiation therapy (often along with chemo) might be an option, but the chances for cure are not as good.

Treating stage II bladder cancer

These cancers have invaded the muscle layer of the bladder wall (T2a and T2b), but no 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.

When the cancer has invaded the muscle, radical cystectomy (removal of the bladder) is the standard treatment. Lymph nodes near the bladder are often removed as well. If cancer is in only one part of the bladder, a partial cystectomy may be done instead. But this is possible in only a small number of patients.

Radical cystectomy may be the only treatment for people who are not well enough to get chemo. But most doctors prefer to give chemo before surgery because it's been shown to help patients live longer than surgery alone. When chemo is given first, surgery is delayed. This is not a problem if the chemo shrinks the bladder cancer, but it might be harmful if the tumor continues to grow during chemo.

If cancer is found in nearby lymph nodes, radiation may be needed after surgery. Another option is chemo, but only if it wasn't given before surgery.

For people who have had surgery, but the features of the tumor show it is at high risk of coming back, the immunotherapy drug nivolumab (Opdivo) might be offered. When given after surgery, nivolumab is given for up to one year.

Certain people may be able to have a second (and more extensive) transurethral resection (TURBT), followed by radiation and chemotherapy. While this lets patients keep their bladder, it’s not clear if the outcomes are as good as they are after cystectomy, so not all doctors agree with this approach. If this treatment is used, frequent and careful follow-up exams are needed. Some experts recommend a repeat cystoscopy and biopsy be done during the chemo and radiation treatment. If cancer is still found in the biopsy sample, a cystectomy will likely be needed.

For patients who can’t have surgery because of other serious health problems, TURBT, radiation, chemotherapy, or some combination of these may be options.

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 often done first to find out how far the cancer has grown into the bladder wall. Chemotherapy followed by radical cystectomy (removal of the bladder and nearby lymph nodes) is then the standard treatment. Partial cystectomy is rarely an option for stage III cancers.

Chemotherapy (chemo) before surgery (with or without radiation) can shrink the tumor, which may make surgery easier. Chemo can also kill any cancer cells that could already have spread to other areas of the body and help people live longer. It can be especially useful for T4 tumors, which have spread outside the bladder. When chemo is given first, surgery to remove the bladder is delayed. The delay is not a problem if the chemo shrinks the cancer, but it can be harmful if it continues to grow during chemo. Sometimes the chemo shrinks the tumor enough that intravesical therapy or chemo with radiation is possible instead of surgery.

Some patients get chemo after surgery to kill any cancer cells left after surgery that are too small to see. Chemo given after cystectomy may help patients stay cancer-free longer, but so far it’s not clear if it helps them live longer. If cancer is found in nearby lymph nodes, radiation may be needed after surgery. Another option is chemo, but only if it wasn't given before surgery.

An option for some patients with single, small tumors (some T3) might be treatment with a second (and more extensive) transurethral resection (TURBT) followed by a combination of chemo and radiation. If cancer is still found when cystoscopy is repeated, cystectomy might be needed.

For people who have had surgery to remove the cancer, but the features of the tumor show it is at high risk of coming back, the immunotherapy drug nivolumab (Opdivo) might be offered. When given after surgery, nivolumab is given for up to one year.

For patients who can’t have surgery because of other serious health problems, treatment options might include TURBT, intravesical therapy, radiation, chemotherapy, immunotherapy, or some combination of these.

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:

• 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) 
• The immunotherapy drug pembrolizumab (Keytruda) plus the antibody-drug conjugate enfortumab vedotin (Padcev)
• 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:

• 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) 
• The immunotherapy drug pembrolizumab (Keytruda) plus the antibody-drug conjugate enfortumab vedotin (Padcev)
• 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 a treatment 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 the next section 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 cancer continues to grow during treatment (progresses) or comes back after treatment (recurs), treatment options will depend on where and how much the cancer has spread, what treatments have already been used, and the patient's overall health and desire for more treatment. It’s important to understand the goal of any further treatment – if it’s to try to cure the cancer, to slow its growth, or to help relieve symptoms – as well as the likely benefits and risks.

For instance, non-muscle invasive bladder cancer often comes back in the bladder. The 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 immunotherapy with nadofaragene firadenovec (Adstiladrin). 

Cancers that 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. 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 the patient wants to continue getting treatment, taking part in a clinical trial of newer bladder cancer treatments might be recommended. While these are not always the best option for every person, they can benefit current, as well as future patients.