How is Bladder Cancer Treated Differently Once it Has Spread Beyond the Bladder?

"That's when bladder cancer becomes truly deadly when it spreads to other parts of the body," Dr. Jay Shah, staff surgeon and associate professor of urology at Stanford University, tells SurvivorNet. "People with bladder cancer don't die of the cancer in their bladder, they die because the bladder cancer spreads to other parts of the body."

Chemotherapy Use for Advanced-Stage Bladder Cancer Treatment

“There’s a small proportion of patients that present with metastatic disease when they’re first found to have bladder cancer, and this is the hardest for us to treat because we don’t really have any curative options,” Dr. Shah explains. This is when a patient finds out that they have cancer in their bladder and that it’s already spread to the lymph nodes, lungs, liver, bones, etc.

The major goal for these patients, Dr. Shah explains, is controlling the cancer.

“So what we’ll do is involve our medical oncology colleagues who will figure out which chemotherapy might work best in your particular case. The truth is, even in the healthiest patients who can get any chemotherapy, because the cancer is so advanced, we don’t want to give the false hope that you’re going to be cured.”

But there is a small percentage of patients whose cancer has spread from their bladder, but it’s only in their lymph nodes nearby. “And while that’s technically considered metastatic disease,” Dr. Shah says, “if we can find a chemotherapy regimen a cocktail of chemo drugs that can kill that cancer in those lymph nodes, we can still try to cure them.”

Cisplatin-based chemotherapy is a particular chemo drug doctors use for bladder cancer treatment as it’s very effective at battling bladder cancer cells, Dr. Shah says. “Unfortunately, if you have bad kidneys or if you have bad hearing, you can’t use cisplatin because it’s very toxic to the kidneys and the ears.”

But, Dr. Arjun Balar, director of the genitourinary medical oncology program at NYU Langone's Perlmutter Cancer Center, tells SurvivorNet that of all the patients who are diagnosed with advanced bladder cancer, doctors are realizing that about 60% to 70% aren’t eligible for the most effective aggressive chemotherapy treatment cisplatin.

“For those patients … we really didn’t have, until recently, very good and effective treatment options,” he says. “And it’s for these specific patients that atezolizumab and pembrolizumab (immunotherapy) has been approved.”

So, if a patient has advanced metastatic bladder cancer and can’t get cisplatin-based chemotherapy, then doctors can try to use immunotherapy to try and prolong the patient’s life and try to control the cancer.

Treatment Option: Immunotherapy

"The advent of immunotherapy, specifically checkpoint-based immunotherapy, has revolutionized how we think about and how we treat advanced and metastatic bladder cancer," Dr. Dan Theodorescu, urological oncologist and director of the Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai, tells SurvivorNet. "Now patients that have metastatic bladder cancer have the option for chemotherapy, the option for immunotherapy and immunotherapy following a failure of chemotherapy if that has taken place."

Immunotherapy is a newer forms of treatment; it works by boosting your body's own immune response to help it stop the cancer. "One of the things that's really alluring about immunotherapy is that it's much more tolerable for patients," Dr. Shah says.

Related: What Are the Side Effects of Immunotherapy for Bladder Cancer?

Dr. Balar says that there are five different immunotherapy drugs that have been approved as second-line treatment in advanced bladder cancer: atezolizumab (brand name: Tecentriq), nivolumab (brand name: Opdivo), pembrolizumab (brand name: Keytruda), durvalumab (brand name: Imfinzi) and avelumab (brand name: Bavencio).

Right now, he says, the approvals for these different immunotherapy drugs are actually after platinum chemotherapy as the second-line treatment of choice. But two of these drugs, atezolizumab and pembrolizumab have been approved for first-line treatment, “meaning the very first treatment that a patient receives for advanced or metastatic bladder cancer.”

Both atezolizumab and pembrolizumab are administrated intravenously over 30 minutes and administered every three weeks, he says. “And the approval is actually specifically for patients who are actually some of our most frail, and those who are not able to tolerate the most aggressive chemotherapy.”

Treatment Option: Targeted Therapy

Other recently approved systemic treatments for bladder cancer include the targeted therapy erdafitinib and the antibody drug conjugate enfortumab vedotin. Erdafitinib targets bladder cancer cells with molecular alterations of fibroblast growth factor receptor (FGFR). Enfortumab vedotin targets bladder cancer cells that express nectin-4.

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